Major Topic

Adrenergic
Anesthetics

Abbreviation Adrenergic
Anesthetics

Major Topic
Cholinergic Corticosteroids

Abbreviation Cholinergic Corticosteroids Cardiovascular

Cancer/Chemo

Arti-Anxlety Agents
Antl-Epileptics
Anti-Depressants

Anti-Anxiety Agents Cardioysscular

Anti-Epileptics
Anti-Depressants

Cancer/ Chemotherapy

Dilretics
H!?oglycemics Miscellareous Narcotic Analgesics Terms/DefinitioDs

Diuretics
Hypoglycemics Misc,

Anti-Histamires Anti-lnfectives
Anti-Psychotics Aspirin/Acetamitrophen/ NSAIDs

Anti-Histamines Anti-Infectives Anti-Psychotics

Asp/Acet/NSAIDS

Narcotic Analgesics Terms/Def

PHARMACOLOGY

Adrenergic

Amphetamines are sympathomimetic amines that cause rapid release of:

. Dopamine in

the brain

. Serotonin in the brain . Norepinephrine in the brain . Acetylcholine in the brain

Copyright

e 2011':0ll

- Denbl Decks

Amphetamines pass readily into the CNS and cause a rapid release of norepinephrine in the brain. Amphetamines increase systolic and diastolic blood pressures and act as weak bronchodilators and respiratory stimulants. They have a high potential for abuse, resulting in tolerance, psychological dependence, and severe social disability. Abuse causes extreme violence and paranoid psychotic behavior Note: Amphetamines and ephedrine are indirectly acting sympathomimetic (sympathetic-type) drugs. These drugs demonstrate tolerance and are orally active, unlike epinephrine and norepinephrine. Therapeutic uses of amphetamines:

. Attention Deficit Hl?eractivity Disorder (ADHD; hyperkinesis) dextroamphetamine (Dexedrine) and a mix of dextroamphetamine with amphetamine (Adderall); (Adderall XR) sometimes used instead ofmethylphenidate (Ritalin). . Narcolepsy dextroamphetamine (Dexedrine) is used to prevent daltime sleepiness

in these patients.

. Weight loss

phentermine (Ionamin)

structurally similar to dextroamphetamine.

1. Tyrosine hydroxylase catalyzes the rate limiting step in the synthesis of norepinephrine (tr'E) and epinephrine. The enzyme is inhibited by metyrosine.
2. Terrnination oftransrnission by NE takes place primarily by the reuptake

ofNE into prejunctional nerves and secondarily into other cells. Monoamine
oxidase (MAO) and catechol-O-methyl transferase (COMT) then play metabolizing the NE.
a

role in

. An alpha-adrenergic receptor blocker (alpha-blocker)

. A beta-adrenergic receptor blocker @eta-blocker)

Coplright O

20ll-201? Dmral

Decks

. Sympathomimetic

. Sympatholytic
. Sympathetic amine . Adrenergic agent

Coplyighr C 201l-2012 DentalDecks

Examples ofselective alphal-blockers used in medicine: . Doxazosin (Cardura) used to fieat hypertension . Prazosin (Minipress) used to treat hypertension . Terazosin (Hytrin) manage mild/moderate hypertension; treatment ofbenign prostatic hyperylasia frPd) . Tamsulosin (Flomax) used to treat benign prostatic hyperplasia (BPH)

***

These drugs selectively block tr1-type receptors but not o2-type

Important: Alphay-blockerc cause orthostatic hypotension, also known as postural hypotension. This is a fainting spell which occurs because ofa rapid fall in blood pressure when moving from the supine to the upright position, as in getting rapidly out ofthe dental chair. The symptoms are similar to simple fainting, however the condition is related to positioning. Note: Other adverse effects include tachycardia, nasal congestion and dry mouth. can also result from centrally acting drugs (i.e., clonidine and methyldopa) and direct vasodilators (i.e., hydralazine and diazoxide)
1. Alpha-blockers inhibit the vasoconstrictor response to epinephrine and levonordefrin. 2. Beta-blockers increase the vasoconstrictor response to epinephrine, but reduce the tachycardia resulting from epinephrine. 3. MAO inhibitors (i.e., phenelzine and tranylcypromtue) should not be used with indirectly acting sympathetic drugs (i.e., Tyramine and anphetamines) and with several other drugs such as opioids, especially meperidine. 4. Epinephrine and levonordefrin have exaggerated effects when given with neuron depleting agents like reserpine and quanethidine.

*** Orthostatic hypotention

:iolcra

-Ji...

Four kinds ofadrenergic receptor blockers: fNorc: Thel are allused to trcsl hlpertension)

L Beta-adreDergic blockers:
. Nonselectir: blocks both betal- and beta2-receptors

. Propmnolol 'Carteolol ' Sotalol . Nadolol . Pnbutolol . Timolol

. Betal-slective: . Atenolol . . Metoprolol .

Esmolol

. Betaxolol

Bisoprolol 'Acebutolol

2. Alpha-adrenergic blockers

. \onselective: blocks both alphat- and alpha2- receptors

'

Phentolaminc

. Phenoxybenzamine

'AlPhat-selective:
. .

Prazosin
Terazosin

. Doxazosin
. Tamsulosin

i.

Centrally acting Nlpha2-agonists: Act through stimulation ofceDtral inhibitory alpha'-adrenergic rc-

ceprors.They inhibit sympathetic cardioaccelemtor and vasoconskictor centers. Stimulation ofalpha-adrenergic rcceptors in the brainstem results in rcduccd sympathetic outflow from thc CNS

'Clonidine . Methyldopa
4.

\euronal depleting agents: cncompasses awide variety ofdrugs having different mechanisms ofaction. depletion ofmediator in thc nouron whatever their specific mechanism, the result is usually the same Ierminal or an inability ofth medialor to be released from the terminal. . Reserpine - depletes granules containing NE in nerve endings, releases NE . Guanethidine - blocks adrcnergic nerve endings by a series ofactions . Metyrosine - inhibits tytosine hydroxylase; used to treat pheochromocytoma

-a

r-ote; Canedilol and labetalol ar nonselective bet|-blockers thai also block alphal-receptors. Tley ate
used for healt failure.

. Epinephrine

(Adrena lin)
Qr'e o - Sy nep

. Phenylephine

hrin e)

. Albuterol (Proventil; Ventolin) . Isoproterenol

4
CopFight O 20ll-2012, Dnral Decks

. Alphal -receptors only

. Betal-receptors only . Both alphal,2 and betar,2-receptors . Both alphal and betat-receptors only

CopyiSht O20ll-2012 - Dental Decks

Note: The adrenergic receptors are divided into the subtypes of: . alphal (o.1) and alpha2 (a2) . betal (B and beta2 (82). l)
Some common adrenergic agonists, their main uss and recptor preference:

. Epinephrine: reverse anaphylaxis, vasoconstriction, bronchodilation

- alphal, alphal, betal, and beta2

. Norpinephrine: vasoconstriction
-alpha1, alpha2. and betal

. Isoprotrenol: bronchodilation
- beta1, and beta2

. Phenylephrine:

nasal vasoconstriction

- alphal. and alpha.r . Albuterol: bronchodilation

- beta.)

. Terbutaline: bronchodilation - betal . Clonidine: antihlpertensive

- alpha2

. \Iethvldopa: antihypertensive
- alpha.'

. Dobutamine: cardiac stimulation

- alphat, and betal

Adrenergic Receptor
Tr"Pe

Characterisfics
Most common alpha rcccptor
Less common alpha receptor Less common beta rcceplor (found on rclls in heafl)

Neurotransmitters that Combine

With Receptors
Norepinephrine or Epinephrine Norepinephrine or Epinephrine Norepinephrine or Epinephrine

Alpha
-4.lpha:

Beia Betal

Most common bcta rcceptor

Epifi ephine (No rep i h ep h r i n e ge n e r a I b'

combines either weaklJ or not at

all)

Remember: Alpha reccptor responses are predominantly ercitatory in nature, while beta receptor ieiponses are \citatory in nature in the heart and inhibitory elsewhere.

Smooth muscle in blood vessels Stomach, intestine

Vasoconstriction
Decreased motility and tone Increased renin seerction Gluconogensis

Kidney Liver
Smooth musclc in blood vessels

Increased rate and forcc ofcontraction lncreased renin secretion

Vasodilation Bronchial, vascular, coronary aneriole, uterine smooth muscle, skcletal muscle Deoeased secretion Pancreas

Liver

Gluconeogenesis

. Tyramine
. Amphetamine

. Epinephrine
. Methamphetamine . Hydroxyamphetamine

CopriShr O

201

l-2012' Dsral

Decks

. Doxazosin (Cardura) . Phenoxybenzamine hydrochloride

(Dibenzy line)

. Phentolanine hydrochloride (Regitine) . Prazosin (Minipress) . Propranolol (Indera l) . Terazosrn (Hytrin)

Cop"ighr O

20 | |

-2012 - Dnral

Deks

Two types ofadrenergic agonists:

1. Indirect-acting: are those that cause the relas of stored norepinephrine at the postganglionic nerve endings to produce their effects. Tyramine and amphetamines cause release of norepinephrine. 2. Direct-acting: are those that interact directly with the alpha or beta receptors.

Direct-acting adrenergic agonists may be receptor selective or receptor non-selective:

. Phenylephine : alphal selective agonist . Clonidine : alpha2 selective agonist . Dobutamine = alphat and betal selective agonist . Terbutaline - beta2 selective agonist
. Albuterol

beta2 selective agonist

. Epinephrine: alphar,2 and betar,2 agonist . Norepinephrine: alphal.2 and betal agonist . Isoproterenol = betal.2 agonist Remember: Some literature refers to direct and indirect-acting adrenergic agonists as direct and indirect-acting sympathomimetic agnts, These terms are almost always slnonl mous. They are agents that bring about tissue responses resembling those produced by stimulation of the sympathetic nervous system.

***

Propranolol is a beta-blocker (speclicall- a non-selective beta-blocker)

Alpha-blockers are medications that act

by competitively inhibiting the action of

catecholamines at the alpha receptor site. They act on blood vessels, causing them to relax. Aipha-blockers are commonly used to reduce high blood pressure and to treat an enlarged prostate. There are two types of alpha-blockers, which are classified according to the alpha receplor that they block (alphal or alpha).

Selective alpha antagonists: only block alphal-recepto$ and are more commonly used ro rreat cardiac conditions (h)pertension) and benign prostatic hyperplasia.

\on-selective alpha antagonists: block both types of receptors and are generally not

used for cardiac conditions because blocking both recepto$ can ca\se tachycardia (rqpid heart beat) and palpitations (pounding he.qrt beat). They are used in the presurgical management of pheochromocytoma and sometimes in treating Raynaud's phenomenon. Some examples of alpha-blockers:

. Doxazosin .
Prazosin

selective alpha,-blocker. Among the alphal-blockers

it is the

prefered

agent for hypenension due to a longer duration of action. . Terazosin selective alphar-blocker. Used to treat benign prostatic hypertrophy.

selectiv alpha'-blocker

lt is rarely

used

to treat hypertension due to

. Phenoxybenzamine and phentolamine both are nonselective alphal and alpha2blockers. They are used in the presurgical management of pheochromocytoma.
*** Aside from hlpotension, which
relatively few adverse reactions.
is a major effect ofalpha-blockade, alpha-blockers cause

unwanted adve$e rcactions.

. Alphar (d.l) receptors . Betal (Br) receptors

. Alpha2 (02) receptors

. Beta,

(82) receptors

8
Coplrighr
@

2011,2012 - Denral Decks

. Vascular smooth muscle

. Presynaptic newe terminals

. Blood platelets
. Fat cells . Neuons in the CNS
.

All of the above

I
Coplrighr O 201

l-2012

Dental Deck!

Arterioles in skin, mucosa, viscera, and k jdney Itertrrdrce verre^,

Presynaptic nerve endings Postsynaptic in CNS

lnhibil rorepinephrine rle3s

Decreased sympathetic tone

. .
Ane(ioles (on.l arkties in skeletal nuscle) Bronchial and uterine smooth muscl

lncreased heart mte

lncaeased force of contmction

There are two main types ofadrenergic receptors:

I . Alpha (o) receptors responsible for most of the excitatory effects such as vasoconstriction and contraction ofthe uterus and spleen. l. Beta (R) receptors - responsible for most ofthe inhibitory effects such as vasodilation and relaxation ofrespiratory smooth muscle.

\ote: Two fnportant EXCEPIIONS to the above: some alpha receptors mediate relaxatio of gastrointestinal smooth muscle, and some beta receptors mediate increases in the
torce and rate of contractions ofthe heart.

-\lpha receptors fall into two groups: 1. Postjunctional alpha, adrenergic receptors are found in radial smooth muscle of
the iris. arteries, arterioles, and veins; in the GI tract. 2. Prejunctional alpha, adrenergic receptors mediate the inhibition of the release norepinephrine.

of

Bela receptors fall inlo t\\o groups:

1. Postjunctional betar adrenergic receptors are found in the myocardium (heart), the intestinal tract smooth muscle, and adipose tissue. 2. Postjunctional beta, adrenergic receptors are found in bronchiolar and vascular

smooth muscle.

. Preganglionic sympathetic neurons

. Preganglionic parasympathetic neurons

. Postganglionic sympathetic neurons

. Postganglionic parasympathetic neurons

10 Copyright
@

2011,2012 - Denral Decks

. Constricts arteriolar blood vessels (vasoconstriction) . Relaxes bronchial smooth muscle (bronchodilation)

Decrease blood volume in nasal tissues

a hypertensive response

. Causes

. Produces physiological actions opposite to that of histamine

11

Copright O 201l-2012

- Dental

Deck

The autonomic neryous system f,4NS/ controls involtntary (smooth)rnuscle and gland activity. Bloodpressure, pulse, sweating, bladder, and rectal sphincter tone are regulated by the ANS. Function ofthe hean, eyes, uterus, urinary bladder, and gasEointestinal tract, from the salivaryglands to thc analsphincter, is govemed and main-

tained by the ANS.

The ANS is a complcx sct ofncurons that originatc from thc CNS fipe.$callf the h'pothalanur; it is composcd of two antagonistic systems. Thc sympathetic nervous system (fron thoraco-hmbar outJlow) ar,d thc parasympa-

thetic nervous system

(ton cratlial-socrdl ou|lo\,t).

The aulononlic nervous system has cholinergic neurons that secrete acetylcholine and adrenergic neurons that secrctc norepinephrine. Prcganglionic ncurons ofboth divisions f.\:l rnla/, eli( and paraslnpathetit) are cholinergic, as arc the postganglionic curons ofthc parastmpathetic branch. Postganglionic neurons ofthc sympathctic branch arc usually adrenergic. Onc rXCl'PltON i s thc sympathetic postganglionic ncurons thal inncflate the swcat glands (thei, arc choli ergic = secrcte acelylcholine). Note: Adrcnergic blocking agents block thc cffcct of impulses transmittcd by thc adrenergic postganglionic ncurons ofthe sympathetic branch. CNS

Somatic NeNous System

Autonomic Nrvous System

Sr_npothctic division

Ach Ach

G----'------'.._-1

vg

Smoolh mmOc

Reproduced wilh permission, f.om Neidle EA. and Yagiela JA. Pnamd .o|o&\ an.l Thetureuti..t for De,tista.
Mosby. 1989.

c}--- ----------,.'<achr :'"dblhd'*,"r,

'meJrlL-E NE n-n *
Hcan Arrr G-<Ach-Smoorhmusclc Glands

r.ts-lAdrcnal

Parasymptlhetic division

Fibcrs ofthe somatic and autonomic nervous systcms, with thc structurcs inncrvatcd by the diffcrcnt libcrs and thc chcmical nrcdiators rcsponsible for lransmission at the various loci. Dashed lines indicatc postganglionic autonomic fibcrs.

Therapeutic indications for epinephrine:

. To alleviate symptoms ofan acute asthma attack . To treat bronchospasm associated with hypotension, as in anaphylaxis . To treat hypersensitivity reactions . Agent ofchoice for anaphylactic reactions (given sublingually or subcutaneoush)) . It is added to local anesthetics as a vasoconstrictor to prolong the activity ofthe local anesthetic solutions, by decreasing the rate of diffusion and absorption from the injectlon site . To restore cardiac activity in cardiac arrest . To relieve congestion ofthe nose, sinuses, and throat

Common side effects: headaches, agitation (anxiei)), and tachycardia.

Important: Epinephrine should be used with caution in patients with high blood pressure and hyperthyroidism. These patients may have an increased sensitivity to epinephrine.

Epinephrlne is the agent of choice for treating an anaphyhctic reaction because ofits stimulatorv effects on both alpha and beta adrenergic receptors.

All ofthe following are desirable efTects ofepinephrine that make it the agent of choice for treating an anaphylactic reaction. . ft has vasopressor activity . It has bronchodilator properties . It causes increased cardiac output . It has a rapid onset ofaction

. The first statement

is true; the second statement is false

. The first statement is false; the second statement is true

Both statements are true

statements are false
12
Copyrighr

. Both

e 20lt-2012

Denral Decks

"Epinephrine reversal' is a predictable result of the use of epinephrine in a patient rvho has received a/an:

. Beta-blocker

. Alpha-blocker . Adrenergic agonist

. All ofthe above

13 Coplright (.) 20ll-2012, Dental Decks

Epinephrine is the agent of choice for treating an anaphylactic reaction because of its stimulatory effects on both alpha and beta adrenergic receptors. Alpha receptor stimulation results in a vasopressor response (elevation ofblood pressLtre). Beta receptor stimulation results in air way dilation and increased cardiac output. In this way, epinephrine counteracts the vascular effects of histamine-related anaphylaxis.

Note: Epinephrine is administered either intravenously, sublingually, subcutaneously or intramuscularly. There is a very rapid onset of action when given by these routes.
Other therapeutic indications for the use ofepinephrine:

. To control superficial hemorrhage . As a component of local anesthetic solutions to prolong duration ofanesthesia .Asthma bronchodilatorproperties

Explanation of answer: One of the best known effects of the alpha-receptor trlocking (antiadrenergiy' is their ability to reverse the pressor action of adrenaline fepl^gents nephrine).In the absence ofblocking agents, epinephrine and norepinephrine both cause the blood pressure to rise. After the alpha-receptors have been blocked by an alphablocker, the pressor effect of norepinephrine is reduced or abolished while epinephrine brings about a fall in blood pressure.
This is because epinephrine stimulates both alpha and beta-receptors in the cardiovascular system but norepinephrine only stimulates alpha-receptors (norepinephrine lacks beta2effbcts). After blockage ofthe alpha-receptors, only the beta-receptors can be stimulated.

Note: A pressor response (produces an increase in blood pressure) is mediated by alphareceptors and a depressor response (produces a decrease in blood pressure) is mediated bv beta. receDtors.

. Drowsiness . Hallucinations . Arthralgia . Dry mouth

14 Coplrighr O 2011,2012 - Dertal Decls

r\'
. \'

If norepinephrine or eplnephrine

wers to stimul|te or combine with the alpba receptors in the eye, which response would you erpect?

. Miosrs (contraction ofthe pupil) . Mydriasis (dilation of

the

pupil)

. Neither ofthe above; norepinepkine and epinephrine do not stimulate or combine with
alpha receptors in the eye

t5
Copyright O 2011,2012 - Denlal Decks

Metoprolol (Lopressor Toprol-XL) is a competitive, betar-selective adrenergic receptor b\ocker (carlioselectlver, which is most similar to Atenolol. It is used in the treatment ofhypertension, acute angina pectoris and may be helpful after a heart attack.
Atenolol (Tenormin) is a competitive, betal-selective adrenergic receptor blocker (cardioselective), wtth alo]ig plasma halflife (1or1g du'ation ofdction.). It is used in the treatment ofhypertension and chronic angina pectoris. Due to its low lipid solubility, Atenolol is renally eliminated, minimally metabolized, and has a low potential for causing CNS side effects compared to lipid soluble beta-blockers (e.g., Propranololl. Metoprolol and Atenolol are both longer-acting and more predictable than Propranolol in producing therapeutic plasma levels. Because they are betar selective adrenergic receptorblockers, they are also safer to use in patients with a history of asthma or bronchitis. -{cebutolol (Sectral) is a betar-selective adrenergic receptor blocker (cqrdio.selective). lt is used to treat hypertension and to control ventricular arrhythmias. It has a low lipid solubilin. $hich reduces its likelihood of producing adverse Crr-S effects. lt also has mild intrinsic s) mpathomimetic activ tly (partial agottist actiritl at beta: rc.eptors) similar to Pindolol.

***

Important points: L \\'ith all "selective" beta-blockers, selectivity for

the betal receptor is lost at high doses. -\s the dose is increased they also block the beta2 receptors, thereby having eff'ects on bronchial smooth rnuscle. l. The most common side effects ofbeta-blockers are weakness and drowsiness.

Organ/Tissue
Heart
p1

Receptor Type

Response to Adrnergic Agonists Increases conduction velocity Increases contraction force Increases conhaction mte Increases cardiac output Constricts cerebral arterioles

PI
p1

0'
Anenoles
ctl

0:
Eve

Dilates skeletal muscle arterioles

Contracts sphincter muscle, producing mydriasis Relaxes tracheal and bronchial muscles
F r.z

ctl

Lung
Intestine

0,
ctr,:

Decreases peristalsis

(ll
Urinary bladder
c[l
PI

Contracts sphincter Contracts trigone and sphincter muscles Relaxes detrusor muscle Excites uterine contactions Inhibits uterine contractions

Uterus

cLl P2

. Levalbuterol

(Xop enex)

.
.

Alb]uterol (Proventi I)
S

almeter ol (S e r e v e n t)
(A lup e nt)

. Metaproterenol . Histamine
. Aminophylline

't6
CoP)right O 20ll-2012 - Denlal Decks

Pharmaceutical agents that bring about tissue responses resembling thme produced by stimul*tion of the sympathtic nervous system are called?

. Cholinomimetic

. Antiadrenergic . Parasympathomimetic

. Sympathomimetic

17

Coplrighr O

20ll-2012

Dental Decks

Asthma is a respiratory disorder characterized by recurring episodes of paroxysmal

dyspnea, wheezing on expiration, coughing, and viscous mucoid bronchial secrelions. The episodes may be precipitated by inhalation ofallergens or pollutants, infection, vigorous exercise, or emotional stress. Management and prevention ofan acute asthma attack: . Epinephrine, levalbuterol, albuterol, salmeterol and metaproterenol are beta. adrenergic receptor agonists. Thus they stimulate the beta recepton in the airway to cause bronchodilation. They are taken via aerosol inhalers and nebulizers. Important: Albuterol is the drug of choice as a "tescue" agent during an acute asthmatic attack.

Note: Arninophylline is an example of a theophylline compound. Theophylline compounds are administered orally as bronchodilators in reversible airway obstruction due to asthma or COPD (chronic obstructive pulmonary tlisea.re). These drugs relax bronchial smooth muscle to improve airway function.

The terms sympathomimetics, syrnpathomimetic amines, adrenergic agonists and adrenergic agents are almost always synonymous.

Epinephrine is the sympathomimetic agent used in dentistry. It is the vasoconstrictor for

anesthetic solulions and the vasoconstrictor component in gingival retraction cords. As a component of local anesthetic preparations, it is used to prolong the duration of local
anesthesia.

In medicine, sympathomimetics are used as pressor agents to maintain blood pressure in vascular shock. They are used as bronchodilators for asthma attacks and for allergic states including anaphylactic shock. Syrnpathomimetics used in medicine include
dopamine, epinephrine, norepinephrine, isoproterenol, and phenylephrine.

Important: Epinephrine is indicated in medicine to treat bronchospasm and hypersensitivity reactions. It is the agent of choice for reversing anaphylactic reactions. lt is used to restore cardiac activity in cardiac arest.

. Reverse an anaphylactic reaction

. Treat hypertension
. Prevent angina pectoris . Reduce anxiety . All ofthe above

18
Copyrighr

e 20ll-2012 - DenblDecks

A fear re|ction activates the sympathetic division the autonomic nervous svstem to result in:

of

. Viosis

. Bradycardia . H)?ertension
. Increased salivation

Copltighr O

201 I

19 '2012 - Dental Decks

The prototypical adrenergic agonist agent is epinephrine, Epinephrine stimulates both beta adrenergic receptors and alpha adrenergic receptors within the sympathetic division ofthe autonomic nervous system. Anaphylaxis is characterized by rapid, extreme reduction in blood pressure and bronchospasms. Epinephrine, upon injectable administration,

will rapidly reverse the hypotension by causing vasoconstriction via the alphal receptor stimulation; it will dilate the bronchial tubes via beta2 receptor stimulation; it will increase cardiac output via betar receptor stimulation on the cardiac muscle.

Epinephrine is: . Ineffective in treating hypertension because of its alpha receptor stimulatory actions
on the vasculature which could cause an even further elevation ofblood pressure . Contraindicated in angina conditions because its cardiostimulatory effects would aggravate this condition . Will not reduce arlxiety but will likely increase anxiety since it has central nervous system stimulatory effects

Activation ofthe sympathetic portion ofthe autonomic nervous system will cause alpharadrenergic receptor activation to result in arteriolar vasoconstriction with an associated elevation of blood pressure leading to hypertension.

. \ot!r -..--,

l. Sympathetic activation ofthe

eye would result in

mydri^sis (dilstion) not

miosis. 2. Sympathetic activation ofthe heart would result in tachycardia, not bradycardia. 3. Sympathetic activation ofthe salivary glands would result in a thick ropeytype salivary flow, not increased salivation.

\liosis (pupillaT, constriction), bradycardia, and increased salivation are physiological effects all resulting from activation of the parasympathetic division of the aulonomic
nen'ous system.

. Lungs
. Plasma

. Liver
. Kidney

20
Coplright O
201

1-2012 - Dmtal Decks

21

CoplriShr O 20ll-2012 - Dental Dcks

The amide-type local ancsthctics that are used in dentistry and metabolizcd by the liver includc:

. Lrd,ocaine

(Xylocairte)

. Ptilocaine

(Citane.tt)

. A(icain (Ultrucaine)

.Mepivacaine(Carbocoite)'Bup|acarne(Matcaine)'Etidocatnc(Dkranest)
Thesc anesthetics are rnetabolized by the hepatic microsomal enzyme system. The products formcd do not have anesthetic actions and are excreted p marily in the urine as metabolites. These agents should be used wjth caution ornot at all in patients with compromiscd livcr function. Notei The most abundant urinary metabolite of lidocaine is 4-hydroxyxvlidine.

Amides are metabolized by three types ofreactions:

l. Dealkylation ofthe amino terminus 2. Hydrolysis ofthe amidc bond L H.vdroxylation ofthe aromatic ring
The amides vary in protein binding. Lidocaine and mepivacaine are bound moderately. Eridocaine and bupivacaine are highly bound. Note: Bupivacaine is more selective for sensory nerves than etidocaine.

Lrdocaine 20" w/epinephnne(

I:

I00,000)

Marcaine 0.5% w,/epinephrine (Bupivacaine Wepinephrine | :200,000)

Articaine 4% Wepinephrine (l : 100,000)

\ote:

Bupivacainc has the longest duration of action ofany dcntal local anesthetic prescntly available.

-{dlerse effects caused by local anesthetics L Efltcts resulting from toxicitl

are categorized into two major grottps:

E11'ects

resulting from allergy

Toricities:
. Too much anesthetic in the bloodstream can cause toxicities to the central nervous system

/Cr\t

and cardiovascular system

. Opioids can increase the systemic toxicity oflocal anesthetics . Esters will show greater toxicity in patients with a hereditary deficiency of plasna esterases. Remember: Esters are metabolized by the plasma enzyme plasma pseudocholinesterase, which is a plasma esterase. . The CNS effects include: restlessness, stimulation. tremors. convulsive seizures followed by CNS depression, slowed respiration and even coma . The cardiovascular effects include: bradycardia and reduction ofcardiac outpr.rt
Allergy-':

. Hypersensitivities or allergic reactions to local anesthetics, particularly from the amides,

are rare. These reactions are manifested as dermatological reactions and edema at the in-

jection site. . Asthmatic wheezing syndromes have occurred in response to local anesthetic injections . Allergic reactions are more prevalent with the ester-type rather than the amide{ype
anesthetics. They also display cross-allergenicity. . Ester local anesthetic allergic manifestations include: nasolabial swelling, itching, and oral mucosal swelling . Ilethylparaben, which was used as a perservative, can a)so cause allergies

. .

Decreases sodium uptake through sodium chamels

ofthe axon

Increases potassium outflow from inside to outside the nerve

. Increases the membrane's permeability to sodium

Increases the excitability of the nerve axon

22
Cop'right O 201| -2012 - Dnral Decks

. Ionized form
. Nonionized free-base form

. Both ionized

and nonionized free-base forms

23
CopFight O 20ll-2012, Dntal Decks

Whcn a local ancsthctic solution is injcctcd ncar thc nervc, thc solutron intcrfcrcs with the uptakc ofsodium from outsidc to insidc thc ncrvc. Thc localanesthctic blocks thc spccific sodium channels thcrcby blocking thc sodium uplakc. This dccrcascs thc ncrvc cxcitability below a critical lcvcl and nervc impulscs fail to propagalc along lhc axon. Sincc axons carry pain scnsations, thcsc scnsalions lvill nol bc carricd and a blockagc ofpain rcsults.

:. : :Notc*;

L Local ancsthctics reversibly block ncrvc impulsc conduction and producc rcvcrsiblc loss ofscnsalion al thcir administcred site. 2. 1-n.u1 onesthctics havc no effects on potassium at thc ncn,c axon. l. Small. nonmyelinated ncrvc fibcrs, which conducl pain and tcmperaturc scnsations, arc affcclcd firsr, follo$cd by touch, proprioccption fpler.fl/re), and skclctal musclc tonc /rroto,r.

D.ug
Shorr Acdtrg

Onret of Bound

Ho*
Supplied

2-5 min Estc. 6-12 min

l5

60

nin

5_8%

C C

/",2%.

tv/,

l0

min

to/r,2%.3%

30 60 min

64.J%

0.5y,. t%. 2'/". 4./,.

l-5

min

45 90 min 60'120

17.5% 55%

c
B

t%. | .5%,

2%. 3%

nin

Long Actlng
5

min

95.6%

0.25%, 05%,0.15'/"

5-10 hr Eslcr

91%
75.60/0

B t%.24/..34/n

i5 min

2-l I'r

Local anesthetic free bases are fat-s oluble (lipophilic) drugs. They are converted to their irater-soluble (hydrophilic.l hydrochloride salts to allow preparation ofan injectable solution. ln solution an equilibrium is established between the ionized and the nonionized tbm.rs ofthe local anesthetic. The proportion ofthe drug in the ionized form depends on rhe pKa of the drug and the pH ofthe solution. At the usual solution pH of 6.0 or lower, most local anesthetics are almost completely in the ionized form.
This is important because only the nonionized free-base form ofthe drug can readily penerrate tissue membranes. Local anesthesia can only be obtained if sufficient free-base is ar ailable. The lower the pKa ofthe drug and the higher the pH ofthe solution or injected tissues. the more free-base will be available. Once the local anesthetic is injected the buffering capacity and pH of the tissues /zornallt T.1) shifts the equilibrium in favor of free-base formation. At physiologic pH of 7.4 approximately 5-20ulo ofthe local anesthetic is in free-base form which is enough to penetrate and cause anesthesia. Ifinfection or inflammation is present, the pH olthe tissues may be acidic and there is a significant reduction in the concentration of the free-base form. In this situation, the local anesthetic may not be effective.

Key point of all this: The potential action olall local zuresthetics depends on the ability ofthe anesthetic salt to liberate the free-base.
Note: Ifyou inject lidocaine (pKa = 7.8) into tissue that has a pH of 7.8, the lidocaine will exist in an equal mixture ofionized and nonionized forms which will be more than enough to Droduce aresthesia.

. Pentobarbital

Secobarbital

. Chloral hydrate . Meperidine

21
Cop)'right O
201 |

,2012 - Denral Decks

. Liver . Lungs
. Plasma . Kidneys

25
Cop)ri8hr O 20ll -2012 - Denial Decks

Traditionally chloral hydrate has been used orally in the preoperative managemnt of the anxious pediatric dental patient. It has an unpleasant odor and a bitter, caustic taste, which can be partially masked in a flavored syrup. Chloral hydrate is rapidly absorbed after oral administration with an onset of 15 to 30 minutes. Its duration ofaction is about 4 hours. For use in children, chloral hydrate is available as a 500 mg/5 ml solution. The usual dose for a child is 50 mg/kg up to a maximum of lg. Important: Children will often enter a period ofexcitement and irritability before becoming sedated. It affects brain centers
that control wakefulness and alertness. Chloral hydrate does not relieve pain.

l. Chloral hydrate is a prodrug and is metabolized to the active metabolite, trichloroethanol. ;'Nnt"q" 2. Chloral hydrate's metabolite (trichloroethanol) may displace warfarin from "'"ee;;l its protein binding sites resulting in an increase in the hypoprothrombinemic response to warfarin.

3. Sedative effects and/or respiratory depression with chloral hydrate may be monitor for increased effect. These additive with other CNS depressants other CNS depressants include ethanol, antidepressants, narcotic analgesics,
and benzodiazepines.
,1. Be

careful when using Chloral hydrate, serious toxicity can result if the

dose is not controlled.

Ester-t!'pe local anesthetics all have an ester grouping within their chemical structure. An
ester grouping is essentially a bridge or link containing

the

COOCH2-configuration.

Amide-tJ*pe local anesthetics all have an amide grouping within their chemical structure. An amide grouping is essentially a bridge or link containing the - CONHCH2-configuration.

Ester-type local anesthetics are mainly available as topical anesthetics and include
benzocaine (which does not have an qmi o terminus end therefore cloes not become charged, thus it is poorl), soluble in water), tet:acaitrrc, and dibucaine. They are also available as medical anesthetic preparations such as propoxyc atne (Ravocaine). Ester-type local anesthetics are no longer available as dental anesthetic injectable preparations because of their relatively high incidence of allergy. Only the amides are presently available as dental injectable local anesthetic agents. These include lidocaine, mepivacaine, prilocaine, bupivacaine, and articaine.

Ester-type local anesthetics are metabolized by the plasma enzyme plasma cholinesterase.
Another name for this enzyme is pseudocholinesterase. This enzyme splits the ester linkage rvithin the chemical structure rendering the anesthetic ineffective. Procaine (Novocaine) was one of the original estr-type anesthetics. When procaine is metabolized by plasma cholinesterase, a highly allergic compound called para aminobenzoic acid lPl BAfor short) is formed. Many patients developed an allergy to PABA. Note: PABA can decrease the effectiveness of sulfonamides (antibiotics).

)iote: Other chemicals that act like local anesthetics:

. Diphenhydramine:

. Ttrodotoxin: found in a number oftissues ofthe puffer or blowfish . Saxitoxin: is produced by certain stmins ofalgae
Remember: Dyclonine hydrochloride is unusual in that it has a ketone linkage between the aromatic moiety and the rcst ofthe anesthetic molecule. It is used as a topical.

antihistamine

. Biliary tract disease

. Type II

diabetes

. Rleumatoid adhritis . Hepatic disease

Coplright O 201l-2012 , Dental Dects

Which trical anesthetic has no place in the routine practice of dentistry?

:'.]

. Articaine

. Cocaine
. Lidocaine

. Bupivacaine . Prilocaine

Coplrighr

O20ll,20l?

- Denral

Deck

*** Remember: All

amides are rnetabolized primarily in the liver, and the metabolites

are then renally excreted.

Priloc^ite (Citanesrl is a local anesthetic ofthe amide class, used for nerve block, epidural and regional anesthesia. It has an intermediate duration ofaction and is longer acting than Lidocaine. Prilocaine produces less vasodilation than do equal amounts ofLidocaine fl is somev'hat less potent thqn Lidocaire). It is available as a 4olo solution with or without
epinephrine, which prolongs the anesihetic effect.

Prilocaine is metabolized to orthotoluidine, a product that can produce mthemoglobinemia, a condition that is characterized by increased levels of methemoglobin in the blood. Note: This methemoglobin is less effective than hemoglobin in catrying oxygen in the blood. Prilocaine is about one-half as toxic as Lidocaine, but since methemoglobinemia is a possible reaction, Prilocaine is not used for patients with hypoxic conditions ofany kind.
Cream is a eutectic mixture oflidocaine 2.5% and prilocaine 2.5% formulated as an oil in water emulsion. In this eutectic mixture, both anesthetics are liquid at room temperature and the penetration and subsequent systemic absorption ofboth prilocaine and lidocaine are enhanced over that which would be seen if each component in cn stalline form was applied separately as a 2.5olo topical cream.

\ote: EMLA

Cocaine is a naturally occurring ester ofbenzoic acid and was the first local anesthetic used in dentistry and medicine. It is potent and extremely toxic, and it is the only local anesthetic that causes definite vasoconstriction (all other locql anesthetics qre va' sodildtors). Cocaine is commercially available in a variety of forms and is applied to mucous membranes of the oral, laryngeal, and nasal cavities for use as a topical anesthetic. Cocaine causes significant euphoria (most likely due to its blockqde of reuptake of dopantine in the bralzl, and abuse can lead to a physical dependence. Despite being an excellent local anesthetic, the risk of abuse and the intense local vasoconstriction it produces prevent cocaine from being more widely used clinically. Important: Cocaine has no place in the routine practice of dentistry.
The pharmacology ofcocaine is unique among local anesthetics in that the drug inhibits the uptake ofcatecholamines by adrenergic newe terminals. It therefore potentiates the ac-

tion ol endogenously released and exogenously administered sympathomimetic amines such as dobutamine, dopamine, or epinephrine. It increases the risk of developing cardiac arrhythmias and hypertension (i.e., cocaine incresses the pressor activity oJ these
$)mP at homim e t ic am
i n es

).

. The pH

rises, thus inactivating the anesthetic

. The pH rises, thus decreasing available free base

The pH decreases, thus decreasing available free base

. The pH remains the same, the extracellular fluid dilutes the anesthetic

28 Coplriglt O 2011,2012, Denbl Decks

A dental rnesthetic carpule contains 1.8 ml of a 27o solution of lidocaine with 1:100,0fi) epinephrine. How much lidocline and epinephrine does the carpule contain?

.3.6 mg lidocaine

and 0.18 mg epinephrine

. 3.6 mg lidocaine and 0.018 mg epinephrine .36 mg lidocaine and 0.18 mg epinephrine . 36 mg lidocaine and 0.018 mg epinephrine

29 Coplriglt O 20ll-2012, Denral Decks

At body pH (7.4), a local anesthetic when infiltrated, will chemically exist as a portion which is ionized (has a proton attached) and as a portion which is non-ionized (ha.s no proton attqched). Note: A proton is nothing more than a hydrogen (H.) alom. That portion which is ionized has difficulty penetrating the nerve and will not be effective. That portion which is non-ionized will penetrate the nrve to cause anesthesia. That portion which is non-ionizd is also known as the free base. The more proportion ofthe anesthetic which is in the free base form. the more effective it will be.
When tissue conditions are normal (p11 7.4), approxrmately 10-207o portion ofan infiltrated local anesthetic is in the form of the free base (non-ionized form). This is enough to penetrate the nerve to cause anesthesia. When tissues are acidic, as in the case of tissue infection, less free base portion exists and more ionized portion is present. There is not enough free base form to penetrate the nerve to cause anesthesia. Therefore, the local anesthetic when infiltrated to the tissue site is not effective at the normal anesthetic doses.

KeJ- to

question: I ml ofa

2olo

solution oflidocaine with l:100,000 epinephrine contains

20 mg of lidocaine and 0.010 mg of epinephrine.

A dental carpule contains 1.8 ml solution. Therefore, 1.8 ml of2% solution oflidocaine with I : 100,000 epinephrine contains 36 mg of lidocaine and 0.018 mg epinephrine.

Epinephrine

(vaso constrictor) is included in local anesthetics for the

following reasons:

. . . .

It prolongs the duration ofaction

It reduces toxicity It reduces the rate ofvascular absorption

lt provides

a hemostatic effect to reduce bleeding at injection site

.7.5 milliliters

. l0 milliliters
.
15

milliliters

. 20 milliliters

30

Coplaigh O 201l-201? Dmtal Decks

The maximum reconmended dose ofa local anesthetic that c|n be tdministered to r child < 10 years ofage is determined by:

'\ ,

' .{ge
. $'eight . Height

. Gender

31

Coplright C 20ll-2012 -

De alDecks

lmportant information to solve qucstions ofthis type:

. There arc 20 mg ofLidocaine in every milliliter of2%o Lidocaine 3n0 mg (maximal recommended dose) - 20 ng (in every mL) = 15 mLs . 20 mg x 1.8 mL ffu every carpule) = 36 mg / I carpule

. 300 mg

36

69 = 3.3 carpttles

(8 cdrpules of 224 Lldocaine can be used)

Remember; Lidocaine has serious drug interactions with beta-blockers and cimtidine that decrease lidocaine clearance 3070 or more. Propranolol, metoprolol, and nadolol are reported to reducc lidocaine clearance due to the decreasg in cardiac output caused by thc beta-blockers. Decreased cardiac output rcsults in reduced liver blood flow which explains the decline in Iidocarne clearance caused by these drugs. Cimetidine also decreases lidocaine clearance, but thc mcchanism ofthe interaction is different. Because cimetidine does not change liver blood llow. it is believed that cimetidine decreases lidocaine clearance by inhibiting hepatic microsomal enz1mes. Lidocaine clearancc may be accelerated by concomitant use ofphenobarbital or phenytoin. Bolh ofthese agents are known to be hepatic drug metabolizing drug inducers, and this is lhe Drobable mcchanism oftheir druc interaction with lidocaine.

Erample: For Lidocaine (2%) wrth epinephrine, a dosage of 4.4 mg/kg should not be
exceeded (wL\imum is 300 ng).

:{ote: I kg = 2.3 lbs 2Yo: 20 mg I mLx 1.8 mL

/l

carpule = 36

mg/l calpule

. Large myelinated fibers

. .

Small unmyelinated fibers Small myelinated fibers

. Large unmyelinated fibers

32

CopyrSh O 20ll-2012 - Denbl Decks

100 mg/kg

. I mg&g
. 300 mg,&g

33
Cop].rjght O 20: l-2012 - Dental

Deks

***

These conduct pain and temperature

Important: They depress the large myelinated fibers last. The small nerves have the greater surface-volume ratio (this accounts for the rapid onset ofaction).
Clinically the general order of loss of function is
as

follows:

l. Pain 2. Temperature 3. Touch 4. Proprioception 5. Skeletal muscle tone

Note: Pain threshold refers to the lowest level ofnain
a natient

will

detect.

Remember: Local anesthetics reversibly block nerve impulse conduction and produce the reversible loss of sensation at their administration site. They do not produce a loss of consciousness. They appear to become incorporated within the nerve membrane or to bind to specific membrane sodium ion channels, restricting sodium pemeability rn response to partial depolarization.

In a tlpical 70 kg adult male, the dose of 7 mghg would equate to a total of490 mgs. Thus. the maximum recommended amount of articaine that could be given to a 70 kg
adult in one appointment is 490 mgs.
The table belo*' shows the following number of dental cartridges containing 1.7 ml vof ume of solution to provide the indicated amounts of articaine hydrochioride 4% and epi-

nenhrine l:100.000.

Number of Cartridges (1.7 ml)

1

Articaine HCL (4%)

(mg)
68 136

Epinephrine l:100,000 (mg)

0.017 0.034
0.051

2
3

204
272

4
5

0.068 0.085 0.102 0.119 0.136

340
408 476 544

6
7 8

. Oral

. Inlalation

.IV
.IM

34

Cop"ighr O 20ll-2012 - Denral Dcks

All of the following are advantages of using nitrous oxide analgesia EXCEPT one. Which one is the EXCEPTIOM
. Rapid onset ofaction

. Lou,ers pain threshold . Produces euphoria

. Pleasant induction . Titratable . Rapid and complete recovery

. Mrtually no adverse effects in

absence

ofhypoxia

. Therapeutic sedative for many medically compromised patients

Suitable for all

ages
35
Copyrighr O

20ll-2012

Dnral Decks

***

The agent used most frequently is nitrous oxide.

Nitrous oxide is a slight sweet smelling, colorless, inert gas. It must always be coupled with no less than 207o oxygen, Nitrous oxide is quickly absorbed from the lungs and is physically dissolved in the blood. There is no biotransformation, and the gas is rapidly
excreted by the lungs when the concentration gradient is reversed. It is recommended that the patient be maintained on oxygen for 5 to l0 minutes after the sedation period.
Dose response for nitrous oxide (always given in mixture with oxygen):

. l0o/o - 20%o: tingling ofhands, feet, body warmth . 20o/o - 40oh: mild sleepiness, relaxation, some analgesia, mind dissociation, heightened auditory perception

. Above 507o: this is too much nitrous

*** Rapid onset: 5 minutes *** Rapid recovery: 5 minutes

\ote: Nitrous oxide

-nausea.

sweatinq

does not provide enough analgesic effect to preclude the use

oflocal

anesthesia in dental surgery or restorative procedures. Local anesthetics must be used along rvith nitrous oxide.

Remember: Nitrous oxide has minimal depressant effects on the cardiovascular system and no skeletal muscle relaxant properties.

*** \itrous

oxide elevats pain threshold

Important points about nitrous oxide: . The main therapeutic effect of nitrous oxide is relaxation/sedation (it is used in conscious sedqtion). Mild analgesia is a secondary effect. It is not a respirutory depressant. . The first symptom ofnitrous oxide onset is tingling of the hands.
. Nitrous oxide
local anesthetic properties. Therefore, the addition oflocal anesthesia procedures in which pain is anticipated. is necessary in . Long term exposure to low doses ofnitrous oxide has been shown to increase the incidence ofspontaneous abortions. Environmental contamination by nitrous oxide can be kept to a minimum by employing a scayengr systm. . Nitrous oxid is stored under pressure (7 50 psi) in sleel cylinderc (in q liquid state) pairltcd
has no

blue. Oxygen is stored in green tanks.

. Nitrous oxide delivery machines come pre-equipped with

a failsafe mchanism that than 20y" oxygen to be delivered to the patient. will not allow less . lt is a nonirritating, colorless gas with a slightly sweet odor and tasteless lt is very sta-

ble and inert chemically at room temperatures. . It has a rapid ons et (blood:gas solubility coelrtcient : 0.47) and termrll'attorr. . It is 1.5 times heavier than air. . Nitrous oxide will diffuse into air-containing cavities within the body faster than nitrogen diffirses out. This results in a temporary increase in either the pressure and/or volume of the cavity depending upon the distensibility ofits walls. This is most noticeabl in the bowel . Nitrous oxide interacts with vitamin Bt2 synthesis in the human body by interfering with the enzyme methionin synthas, deplting the body of vitamin -B12. When nitrous oxide is used heavily and over an extended period of time, vitamin 812 depletion will probably become a major problem, as it can cause brain and nerve damage.

. Halothane

. Enflurane . Isoflumne . Sevoflurane

. Desflurane

CoplriSh O

201 I -20 12 - Denral Deck.

37

Coplrighl O20ll-2012

- Dental Dck!

Inhalation ancsthctics arc drugs which are vaporized tiom thc liquid form and inhaled to produce geneml anesthesia. Thcse diveisc dnrgs are relatively simplc lipophilic molccules ranging from cthcrs such as halogenated hydrocarbons such as halothane and halogenatcd ethcrs such as isofluranc, cnflumne, scvoflumne, and desflumnc. Note: Vaporization ofthcsc liquids occus in a vaporizer and dclivery to the patient occurs through an anestbcsia machine via a nasal mask. Essential Components of Anesthesia:

. Analgesia - perception ofpain eliminated

. Htrpnosis - unconsciousness

. Depression ofspinal motor rflexes . Musclc rclation Hypotheses of General Anesthesia:

. Lipid Theory: bascd on the fact that anesthetic action is corrclatcd with the oil/gas coefficicnts.
The higher the solubility ofancsthctics is in oil, thc grcater is thc anesthctic potency. . Protein (Receptor) Theoryi based on the fact that ancsthctic potcncy is conelated with thc ability of ancsthctics to inhibit enzynes activity of a pure, soluble protein. Also, attempts to cxplain thc GABAA rcceptor is a potcntial targct of ancsthctics acton. . Binding theory: anesthetics bind to hydrophobic portion of the ion channel.

Phermacokinetics of lnhsled Anesthetics: . Amount that rarches the brain - Indicatcd by oil:gas ratio (lipid soluhili\,) . Partial Pressure of anesthetics - 5% ancsthctics = 38 mmHg . Sofubility of gas into blood (blood-g.ts solubiliry coelficient) - Thc lower the blood:gas ratio, the morc anesthctics will arrivc . Cardiac Output
- Incrcased CO = greater induction time

at thc brain

\lAC hean

alveolar concentration).
50o%

. A measurc ofpotency . I MAC is the concentration necessary to prcvent responding in

ofpopulation

. Valucs ofMAC are additive: - Avoid cardiovascular depressive concenration ofpotcnt agcnts

Epinephrine, a vasoconstrictor' is included in dental local anesthetic preparations for the following three reasons:

L It prolongs the duration oflocal anesthesia.

2. To provide a hernostasis such that local bleeding is conlrolled or reduced.
3. To delay the

absorption ofanesthetic into the systemic circulation thus reducing the

chance of systemic toxicities.

Which stage of general anesthesia begins with unconsciousness?

Stage Stage Stage Stage

I
II

.
. .

III
IV

CopFighr O

201

38 l-:012 - Dental Decks

. The first statement

is true; the second statement is false second statement is true

. The first statement is false; the . Both

statements are true

. Both statements are false

39

Coplrighl O

201

l-2012 - Dotal Decks

Four stages ofgeneral anesthesia:

Stage I: Amnesia/analgsia Stage II: Delerium: begins with unconsciousness and ends with loss ofyelid rellex, purposcless movements and h)per-reaction, dilated pupils, reflex vomiting, tachycardia, and hlTe.tension . Stage llli Surgical rnesthesia: four planes with progressive loss ofreflexes and n1uscle control . Stage IV: Medullary paralysis: cessation ofrcspiration, ending with death without proper trearment

Notei These four stages ofanesthesia apply to the inhalaflts and not to the intravenous general anesthetics.
Agents used lbr generrl anesthesia:

. Inhalafion agentsi volatile halogen-containing Iiquids

- Halothane: poses a risk with epinephrine; associated with hepatitis; poor skeletal muscle rclaxant. llowever, it is one ofthe mor widely used anesthetics for general surgical anesthesia. - Desrlurane, sevoflurane, isoflurane and enflurane: pose Jess risk with epinephrine; not associated wirh hepatitis; good skeletal muscle relaxants.

\ote:

Nitrous oxide fN,O) is not considered a gencral ancsthetic since hlpoxic levels are required to producc anesthesia. It is considcred a sedative. It is used alone to produce sedation or in combination with the above agenrs to supplement the anesthetic response. lt is a gas at room temperaturc and pressure.

.Intrar'enous agents: . f ltrashort-acting barbiturates: thiopntal (Pentothal) and methohexit^l (Brei[al) . Benzodiazepines: di^zeptm (yaliun), tuidazol^m (Versed.), lor^rcp^m (Ativan) ^nd . \eurolep(ic-opioid combinations which are called neuroroleptanalgesics combine fentanyl loprorrl.) trd d.operidol (a phenothiazine)
. Other agents: . Propolol (Diprivan), a short-acti g hypnotic agent; vasodilator . Ketamine (Ketalar). is considcrcd a dissociative anesthetic. It blocks N-methyl-D-asparate A,VDA) (glutanale) rccpetors. Nofer In some circumstances, ketamine has been known to produce illusions or hallucinations that are enhanced by environmental stinruli {rpon eme.gence liom anesthesia. Diazpam is givn with ketamine to avoid this. . Etomidate (Anitlate): is a carboxylated imidazole derivative \\.hich acts similar to the ultrashonacting barbituratcs.

Nitrous oxide is unable to produce general anesthesia except ifit is given at concentrations greater rhan 80q'o. At thesc concentrations, thc lack ofoxygen would cause hypoxia in the paticnt. lnhalant aneslhetics such as halothane and isoflurane can produce general anesthcsia al concentrations appro\imating 3-5%. As such they are very useful in anesthesia.
is used to produca sedation and mild analgesia. It is usually used in concentrations of30509'o along rvith pure oxygen. lt is a colorless, nonirritating gas at room tempemture and prcssuc, and is not flammable nor cxplosivc. The onset of sedation is within 5 minutes and the recovery is lu:t as rapid. lt is excreted unchanged by th lungs. The most common complaint from patients

\rtrous

taking nitrous oxide is mild nausea.

\ote: -\l*ays give patient

.

10070 oxygen at thc end

ofthe pfocedure to prcvent diffusion hypoxia.

-\dlerse effects ofnitrous oxide:

Decreased mental performance, audiovisual ability, and manual dexterity

..A.t high doses and/or high exposure: reduced t'ertility, spontaneous abortions, neurological and lrdney disease as well as bone marrow suppression
Nrlrous oxide is contraindicated in patients:

. . . . . . . . .

Head injury

With bowel obstruction

Pneumothorax Middle ear and sinus disease With upper respiratory infections

COPD (emph),sema ol bt'onchitis) In the first trinester ofprcgnancy With whom communication is difficult fi.e., autistic ptttietlts) Having a contagious disease since it is difficult to sterilize entire tubes
hou,'s./ causes bone marrow depression.

Important; Prolonged exposure (e.g., morc than 24

. Water

. Bisulfites . Lidocaine . Epinephrine

(v as oc o nstri c to

r)

40
Copyrighr O

20ll-2012, Dmral

Decks

Of the amide-type local anesthetics, which is the only one that is metabolized in the bloodstrcrm rather than the liver?

. Articaine (Septocaine, Zorcaine) . Vepivacaine

(Ca rbocaine)

. Lidocaine (Xylocaine)
. Prilocaine (Citanest)

. Bupiv

acaine (Marc aine)

41 Copyrighr @

20ll

201? - DentalDecks

Patients may exhibit hypersensitivity to sulfites contained in some anesthetic solutions. Sodium metabisullite prevents the oxidation (deterioration) ofthe epinephrine vasoconstrictor in those commercial preparations containing epinephrine. Most ofthe patients reacting to bisulfites have a history of asthma and the airway is hyperactive to the sulfites. Allergic reaction usually results in an asthmatic slardrome ofwheezing and bronchial constriction. Bisulfites are present in only those commercial preparations containing vasoconstrictor. Preparations without vasoconstrictor such as mepivacaine 3olo (Carbocaine
37o) do not contain bisulfites.

Important: All local anesthetics except cocaine are vasodilators, however, mepivacaine has Iess of a vasodilator effect compared to the others and, therefore, is the drug chosen \\'hen a vasoconstrictor is not used with the local anesthetic.

\ote: Hypersensitivity

or allergic reactions to local anesthetics, particularly the amides,

are much more rare than allergic reactions to the bisulfites.

.\nicaine (Septocaine, Zorcaine) isan amide-type local anesthetic. However, it is chemicalll unique in that it has an ster group attached to its molecule which can be acted upon by plasma cholinesterase to render it ineffective. Therefore, it is the only amide q hich is metabolized in the bloodstream and not the liver. Rapid metabolism ofthis ester
bond gives it a short

halflife.

as articaine HCL 4% solution with epinephrine l:100,000 ard as articaine HCL 4olo solution with epinephrine l:200,000. It is indicated for local, infiltrative, or conductive anesthesia in both simple and complex dental and periodontal procedures. The onset ofanesthesia following administration ofarticaine has been shown to be I to 6 minutes after injection. Complete anesthesia lasts approximately I hour.

.{nicaine is supplied

Articaine is contraindicated in patients with hypersensitivity to local anesthetics ofthe amide type or to sodium bisulfite.

.
.

10olo decrease 25olo decrease 50olo decrease

in the time for normal sensation to retum in the time for normal sensation to retum in the time for normal sensation to rehrrn

80oZ decrease in the time for normal sensation to retum

42 Coprighr O
201

l-?012 - Dental Dects

Phentolamine mesyhte (OraVerse) is a drug used to reverse coft tissue anesthesia and th associatd functional deficits resulting from a local dental anesthetic containing a yssoconstrictor. Which statement best dscribes its mechansim ofaction?

. Prevents

the influx ofsodium into the neuron bv blockins neuronal channels

. Causes vasodilation and increased blood flow in iniection area . Prevents the efflux ofsodium out of the neuron . Causes vasoconstriction and decreased blood flow in iniection area

43
Coplright O 201 I -20 l2 - Denral Decks

Thus if a local anesthetic such as lidocaine with epinephrine normally takes about 180 minutes to wear off, after phentolamine injection, the anesthetic will wear offin approximately 90 minutes. This represents a 50o% decrease in time for normal sensation to be retored.

Note: OraVerse dose is based upon the number of cartridges of local anesthetic with
vasoconstrictor administered.

. l/2 a caftridge (0.2mg) of OraYerse if ll2 cmidge of anaesthetic was administered . I cartridge (0.1mg) of OraYerse if I carhidge of anesthetic was administered . 2 cartridges (0.8mg) of OraVerse if2 cartridges ofanesthetic were administered
Note: OraVerse
(so

lutionJbr injection/dental cartridge) is administered

as a submucosal

iniection,

Phentolamine rnesylate (OraVerse) rs an alphat-adrenergic receptor t locker. Phentolamine mesylate competitively blocks alpha-adrenergic receptors to produce brief an-

tagonism
r

of

circulating epinephrine and norepinephrine and antagonism

of

the

asoconstrictor in the anesthetic preparation. This results in vasodilation of the blood vessels. The local anesthetic is thus carried away at a more rapid rate from the injection site resulting in a more rapid retum to normal nerve sensation.

All of the following drugs are benzodiazepines EXCEPT one. Whtch one is the EXCEPIIOM
, Chlordiazepoxide
(Li brium )

. Diazepam (Yalium) . Flvazepam (Dalmane) . Mrdazolam (Versed)

Alprazolam (Xanax)

. Zolpldem (Anbie )
. Tiazolam (Halcion) . Oxazepam (Serai . Temazepam (Resortl) . Clorazepate
(Tr anxene) Coplri8h
Cr

44

20ll-2012, DfrtalDecks

. CNS depression (drcwsiness and sedation)

. GI disturbances (nausea, vomiting and diarrhea)

. Confusion

. Respiratory depression
. Disorientation . Ataxia

45
Coplyighr O
201

l-2012 - Dental Deck!

The benzodiazepines are used as oral preparations to alleviate anxiety and to inducc sleep, and intravenously to cause conscious-scdation for outpatient surgery. Benzodiazepines act by potentiating the action ofGABA, an amino acid and an inhibitory neurotansmitter, which results in increased neuronal inhibition and CNS depression. Tolerance and physical dependence can occur with prolonged high dosage. They seem lo be much saler than barbituratcs. Other useful properties include being an anti-conwlsant and a skeletal musclc relaxant. Pharmacological effects of benzodiazepines: antianxiety, sedation, anticonvulsant, amnesia, and skeletal muscle rclaxation.
Adverse effects:

. CNS e{Iects
a cqr)

fatigue, slurred speech, drowsiness/sleepiness and conf'usion (do not drive

. Gl effects dry mouth, nausea . Other effects hypotension, muscle relaxation

Benzodiazepines used orally as tmnquilizen: chlordiazepoxide (Libtittm), di.azepam (Valirn). alprazolam (Xonax) and lorazepam (Ativan).Those used as hypnotics to overcome insomnia: flurazepam (Dalmane) andtiazolam (Halcion). Drazepam (Valium) ar'd Clonazepam tKlonopin ) can be used as anticonvulsants. Midazolam (Ilersed) comes as a liquid for preoperative sedation in children and as injectable for IV conscious sedatron.

\ote:

Benzodiazepines should never be taken with any form ofalcohol. Serious potentiation ofthe sedative eflects ofeach will occur leading to unexpected inebriation and respiratory depresslon.

Important: Zolpidem (Ambien), eszopiclone (Lunesta), and zaleplon (Sonata) are anti-insomnia age s (cdlled GABA-BZ Agonisls).These agents appear to act through the potentiation of GABA
on benzodiazepine receptors, especially the omega-1 subunit. Note: They have shown no potential for causins addiction.

The benzodiazepines have

clinically useful antianxicty, scdative-hypnotic, anticonvulsant and skele-

ial muscle relaxanl propcrties. They exert their main effect on central GABA-nergic neurons. With nomral dosrng, thc benzodiazepines have little effect on respiratory systcms in healthy individuals.
The benzodiazepines (especially diazepam, lorazepam and midazolan) arc important adjuncts in rhe practice of ancsthesiology. They may be used as preoperative scdatives and induction agents, as \\ cll as supplcrncntal agents for the maintenance ofanesthesia. Important Thc benzodiazepines, barbiturates and narcotic analgesics all produce sedation and have the ability to produce de-

pendence.
The pharmacokinetics ofindividual benzodiazepines difler, and thcrelbre there is a wide range in speed of onset and duration of action anrong these compounds. Following oral administration, most ofthe benzodiazepines are rapidly absorbed and highly bound to plasma protein. ln general, most of the metabolitcs are conjugated with glucuronic acid and excreted in the urine and f-eces Note: cl,-Hydroxylation is a rapid route ofmetabolism that is unique to triazolam, midazolaln, and alprazolam. This accounts for the vcry mpid metabolism and short sedative actions ofthese drugs.
1. The term tranquilizer rcfers to a drug that promotes tranquility by calming, soothing, quieting orpacifying without sodating or depressant e{lccts. Antipsychotic agcnts arc considered to be major tranquilizers and antianxigty agents fuenzodiazepites) are considercd to be minor tranquilizers.

2. For the treatment of insomnia due to anxiety the benzodiazepines llurazepam,

temazepam and triazolarn are usually prescribed. 3. lmportant: Flumazenil (Mazicon), a bcnzodiazepine antagonist, may bc used to rcverse thc residual effects ofbenzodiazepines in the evcnt ofan overdose. 4. tfthe benzodiazepines are i.effective in helping with insomn ia, zolpidem (Ambien), eszopiclone (L nesta), or zaleplon (Sonata) are ot\en weful. Thesc are anti-insomnia agents (called GABA-BZ Agonists).

. GABA (gamma-aminobutyric acid) receptor

. Norepinephrine rceptor . Dopamine receptor

. Serotonin receptor

46
Copyrighr O 2011,2012 - Dental Dects

Rash, itch

. Vouth, throat ulcers

. Drowsiness, fatigue
. Difiiculty with urination

17
CopltiShr O 20ll-2012 - Dental Decks

Buspirone (BuSpar) is an orally administered antianxiety agent with a short halfJife (24 hours). It is not chemically related to the benzodiazepines, or any other anxiolyic agent. Buspirone also differs from other antianxiety agents in that it does not possess anticonvulsant or muscle relaxant properties, does not impair psychomotor function and does not cause sedation (lacks CNS depressant activiry) or physical dependence.
The exact mechanism ofaction olbuspirone is unknown. However, it has a higher affinity for serotonin receptors in the CNS and a lesser aflinity for the benzodiazepineGABA receptors.

Important: The antianxiety effect is achieved via a partial agonist effect on CNS serotonin 5 -HTla receptors that occurs without affecting the benzodiazepine receptors or
causing CNS depression.

Remember: GABA-BZ agonists have a chemical struchrre that is dissimilar frorn those ofthe benzodiazepines and on the sedative hypnotics. These agents appear to act through the potentiation ofGABA on benzodiazepine rceptors, especially the omega-l subunit. They are used primarily for insomlia. They have exhibited some anxioll4ic action but they have little effect on skeletal muscle or seizure thresholds. They appear to have minimal disruptive action on the normal sleep cycle, thus preserving deep sleep. Note: They have shown no potential for causing addiction. Examples include Zolpidem (l mbien), eszopiclone (Lunesta), and zaleplon (Sonata). -fhese drugs have short halflivs f1 /o 2
how s).

Diazepam is prescribed in the treaftnent ofanxiety, nervous tension, muscle spasm, and as an anticon!'ulsant. Contraindication to use: Acute narrow angle glaucoma.

It is used intravenously as the agent ofchoice to reverse status epilepticus induced by a local anesthetic overdose. Diazepam affects the limbic system olthe brain lcontrols emo/iori. It has a high therapeutic index, produces some degtee ofannesia, and can be locally irritating to tissue and may produce local thrombophlebitis when given intravenously.

\ote:

Propylene glycol, which is in the

ry mixture, is the main

cause ofthrombophlebitis.

. Ulhashort-acting

. Short-acting . Intermediate-acting . Long-acting

48
Coplright O 201 I -20 l2 - Denral Decks

The brief duration of general anesthetic rction of an ultra-short-acting barbitumte is due to what factor?

. Rapid rate ofmetabolism in the liver

. Lorv lipid solubility, resulting in a minimal concentration in the brain . High . Rapid
degree

ofbinding to plasma proteins

rate ofredistribution from the brain to peripheral tissues

. Slow rate ofexcretion by the kidneys

49
Coplright
@

201t-2012 - Dental Decks

The length ofaction can be related to the lipid solubility with the ulhashort being the most lipid solubJe and the long acting having thc least lipid solubility. Thcy are mctabolized in the liver, These drugs possess serious drug dependence potential. They do not possess significant analgesic propefiies. The

length ofh)?notic action ofthe four different classes after a single dose are as follows:

. Ultrashort-acting: 5 to 20 minutes . Short-acting: I to 3 hours . Intermediate-acting: 3 to 6 hours . Long-acting: 6 to l0 hours

Agents:

. Ultrashort-acting: for . Short-actingi for

(Nenbutal).

induction of general anesthesia. Examples include thiopental (Pentothal)

and methohexital fBr"evildl,.

treating insomnia. Examples include secobarbital (Seconal) and pentobarbital

and

. Intermediate-acting: for treating insomnia. Examples include amobarbital (An.vtal)

bital lButisol). . Long-acting: for treating certain types ofseizures. Examples include phenobarbital
phobarbital (Mebarul ) and pi'n]id.one (Mysoli ne).
(Z

bfiabat

uminal),me-

Remember: Barbiturates do not possess analgcsic properties.

Important concept for anticonvulsant effect of lo.rg-acting barbittrates (i.e. phenobatbital)t Ba'rbrrurates rvork by inhibiting the depoladzation ofneurons by binding to the GABAreceptors, which enhances the iransmission ofchloride ions. They also increase the threshold for electrical stimulation ofthe motor conex. Remember: Benzodiazepines work similarly to barbin-rates, but they also increase the number of chloride channels whilc facilitating the transmission of chloride ions. This suppresses the :pread of seizlrre activity but does not abolish abnormal discharge from a focus. The cause ofdeath from acute barbiturate poisoning or overdosage is respiratory failure. Other ad\erse reactions include CNS depression, euphoria, and habituation. The most important therapeutic measure to be taken in a case ofbarbifurate poisoning is to assure adequate respiration.

\ote:

Remember; These agents will maintain anesthesia only while in the brain. Because of their high lipid solubility, these agents will rapidly leave the brain for other tissues; thus the patient wakes up within a few minutes of administration.
Eramples of ultra-short-acting barbiturates include thiopental (Pentothal) and methohe\ital (.B/?l,tal/. These agents are administered by intravenous injection.

Contraindications to the use of ultra-short-acting barbiturates for general anesthesia: . Porphyria . Lir er dysfunction (thet- are metabolized in the liver)

. Emphysema . Previous addiction to sedative hypnotic drugs

Remember: These drugs have the ability to produce dependence.

All of tle following statements concerning barbiturates are true

. Barbiturates may increase the half-lives of drugs metabolized by the liver

. Barbiturates

depress neuronal activily by increasing membrane ion conductance (primarily chloride), reducing glutamate-induced depolarizations and potentiating the inhibitory effects of GABA
the barbiturates exhibit a steeper dose-response rela-

. Compared with benzodiazepines,

tionship

. Barbiturates may precipitate acute porphyria in susceptible patients

50

CoplrightO 20ll-2012 - Dnral Decks

All the following are classified as antiepileptics fiXCEPI one. Which one is the.EXdEPIlON?
. Gabapenth lN euro h t i n)
.
C

arbamazeplne (Tegretol)

. Phen-\1oin (Di lantin) . p Tsp1fsisns

(Ryt hn
o l)
i n a I)

. .

Phenobarbttal (Lutn Dlazepam (l/alium)

. Yalproic

acid, (Depakene)

. Ethosuximide

(Zaron

in)

. Primidone (Mysoline)
51

Copright O 20ll-2012 - Dental Decks

This is falsel barbiturates may decrease the halflives of drugs metabolized by the liver. Barbiturates induce the formation ofthe liver microsomal enz),nes that metabolize drugs. This leads to an increased clearance ofthe affected drugs and possibly leads to a
decrease in the drugs effectiveness.

***

The uses ofthe barbiturates are determined by their duration ofaction: 1. The ultrashort-acting agents are used intravenously for the induction of general anesthesia. For extensive procedures, they are used to induce stage III surgical anesthesia. For very brief procedures, they may be used alone. 2. The short-acting agents can be used orally for their hypnotic, calming effect. These agents can be given preoperatively, before a dental appointment, to allay anxiety. 3. The intermediate-acting agents can also be prescribed to relieve anxiety before a dental appointment, although their effects will last longer than those of the shoft-acting agents. These agents are used for daytime sedation and for the treatment of insomnia (they suppress REM sleep). ,1. The long-acting barbiturates are used primarily for daytime sedation and the treatment ofepilepsy. Generally the primary pharmacological effects ofthe barbiturates involve the brain and depression ofl. At sedative doses barbiturates do not effect or have spinal cord (CNS linle effect on the cardiovascular and respiratory systems. Barbiturates are metabolized in the liver. The chronic use ofthe barbiturates causes an increase in liver microsomal enz)me activity that appears to be the result ofincreased synthesis ofenzyme. These drugs possess serious drug dependence potential. They do not possess significant analgesic

DroDerties.

*** Propsfenone
ular tschlcardias.

/Rr1/rnol./ is an antianhlthmic agcnt uscd to trcat both vcnlricuiar arrhythmias and supmvcntric-

.\seizureisanakcrationinbchavior,functio,and,/orconsciousncssthatrcsultstiomanabnormalclcctricaldischargc ol ncurons rn thc brain. Epilepsy, or th tcrm scizurc disordcr, is uscd to dcscribc chronic unprovokcd rccurrcnt srizur.s. Serzurcs as classiflcd as eilher panial or generalized, bascd on horv thc abnormal brain activity bcgins. . Partial seizures: when scizurcs appcar 1() rcsult from abnormal activit] in just onc pan ofthe brain. . Generalized seizuresi seizures that sccm to in\rclve all ofthc brain. Fourrypcs ofgcncraiizcd seizurcs cxist; absence tnlso Lalle.! pdit md1). myoclonic, ttonic and tonic-clonic scizurcs (ulso culled grand nal).
F!.: xrr.ir antiepifeptic /.rnti@t1fllsant) dr$gs, thc cxact mechanism for rcducing scizDrc activity is not clcarly un-

Jrrsii\id. All incrcasc thc threshold ofthc CNS to convulsivc stimuli or inhibit thc sprcad ofscizurc activiry Thc
:nri,r!1:!'prlc drugs

/,{fDrl

can bc groupcd into thc following classes:

lHldantoinsfPhen]toin/D//drrnrlisuscdinthctrcatmcntoftonicclonic(grandnal)sciz\\rcs.ltprolongsthc

.ti.cri\c rcfBctory pcriod by blocking ncuronal sodium channcls. Phcnytoin-induccd gingival hyperplasis is common and ma] pa.tially or totally obscurc thc crcwns oftccth. Thc ratc ofdcvclopncnl oflhis condition can bc diminishcd by proper oral hygicnc. L GABA analogs: The cxacl mcchanism ofaction ofvalproic acid /Dcpdkdn.i and thc ncwcr GABA analogs is not clcarly undcrs@od. Al1 ofthcm incrcasc thc actions ofGABA, in inhibilory ncurotransmittcr Thcy may inhibit thc voltagc-dcpcndent sodium channcl, thcrcby stabilizjng thc ncuronal membranes. [xamplcs oflhc ncwcr GABA analogs include: gabapcntin (Neuro tin), divalprocx sodium fDryakote), fclbamzlc (Felbaror, lamotriginc (Lan ida l) , prc9abal;n lLlrirc ) , t;a$abirc lcabitril) , and ropiftr..,arc (Topumar) . 3. Succinimides: Ethosu\imlde (Zaro tifi)t \tscd in thc trcatmcnt of abscncc scizures. 4. Barbituratesi Phenob^rbital (Lut inal.)wo*s by inhibiting dcpolarization ofncurons by bindinglo the GABA rcccptors, which cnhanccs lhc transmission ofchloridc ions. Primidone (t|r.!o/ir?i is mctabolizcd lo phcnobarbital and phcnylcthylmalonanide /PtM,4/, which havc anticonvulsant activity. 5. Benzodiazepines; work similarly to barbituratcs, but thcy also incrcasc thc numbcr ofchloridc channcls whilc facilitating thc transmission ofchloridc ions. Examplcs includc diazepam (lhlium), clo azcpam (Klonopnt), and lomzcpam /,lrl|rl,r. Not: Di^zeprm (Ilalium) is uscd for status cpilcpticus and in cmcrgcncy trcatmcnt ofseizures. May cdusc drcwsrncss. dr7lincss. dnd ata\id. 6. Misceffaneous: oxcarbazcpi^c (hilepttrl),lcvctiftccl^m (Kepptu), and c rbgm zepine (hegreol).C^rbamazepine is uscd as prophylaxis for partial scizurcs ilh complcx symptomatology including psychomotor and tcmporal lobc scizurcs. It is also uscd to treat tonicclonic scizurcs /grdrd nd, and trigcminal ncuralgia. It rarcly
causcs aplastic ancmia,

. Imipramine Qof'anil)

Amitr ipty line (E I ai l)

. Desipramine (Norpramin)
.
N

ortiptyline

(P am e I o r)

. Doxeprn (Sinequan)

52 Coptrighr O
201

l'2012 - DeDtal Decks

Which drug is the current drug ofcholce for the treatment ofthe manic phase ofbipolar disorder (or manic4epressive syndrome)?

. Phenobarbital

. Irnipramine . Lithium . Haloperidol

53

Coplrighl O 201l-2012, Dental Dcks

The tricyclic antidepressants are generally considered to be the drugs of first choice for the treatment ofunipolar disorder (depresslor). These drugs inhitlit the neuronal re-uptake of norepinephrine and srotonin (5-HT) in the brain. This results in the potentiation oftheir neurotransmitter actions at postsynaptic receptors.

Important: Amitriptyline displays the greatest anticholinergics effects (especially xerostomia), desipramine the least. Drowsiness is the most frequent CNS adverse reaction. Anticholinergic adverse side effects include: dry mouth, constipation, blurred vision and tachycardia. The selective serotonin reuptake inhibitors (S,SR1s) have revolutionized the treatment ofdepression. The most important clinical distinction ofthe SSRIs from all other antidepressants is their very high specificity for blocking the reuptake of serotonin. Fluoxetine (Prozac:)is the prototlpe and has the longest half-life. Paroxetine (Paxil), Sertraline (Zololi) and Fluvoxamine (Luvox) have shorter half-lives and can be given once daily. Citalopram (Celexa) and escilalopram (Lexapro) are used for generalized anxiety disorders. These drugs are also effective for treating panic attacks. Side effects include nausea. headaches, anxiety, agitation, insomnia, and sexual dysfunction.

Bipolar disorder for manic-clepressive syndrome) is characterized by cyclical changes in affectir e state between the manic and depressive phases ofbehavior Bipolar patients cycle ber$ een rhe trvo aflbcted states.
are by far the most important drugs for suppressing mania in patients with affective disorders. It is not useful for the acute manic episodes. Lithium can prevent the occurrence ofboth the depressive as well as the manic episodes in some but not all the patients.

Lithium salts

Antidepressants are often administered with lithium to manage the depressive phase ofthe illness if lithium alone is not sufficient. Note: Lithium works inside the cell to prevent the formation of inositol triphosphate and diacylglycerol. These substances serve as second messengers within the CNS and may have widespread influence on neuronal function.

Approximately 2570 of patients who suffer from mania do not respond to lithium. Carbamazepine (qtl anticonvulsant) andvalproic teid (also an a ticonwlsant) may be effective in
some relractory cases. Note: Carbamazepine blocks sodium channels and valproic acid blocks both sodium and calcium channels. Neurofeptic agents (also referrecl to as anti-psychotic agents or msjor trqnquilizersl are used in the acute manic episodes. Chlorpromazine, which is a phenothiazine, and Haloperidol, *'hich is not a phenothiazine but acts in a similar fashion, are effective in quelling the exheme mania and psychotic behavior

i\ote*.

;;.-1

1. The most common side effects of lithium, including Gl irritation, fine hand ftsm61 muscular weakness, polyuria, thint, sleepiness, and a sluggish feeling, are often associated with initial therapy and usually fade within I to 2 weeks. 2. Severe intoxication results in vomiting, diarrhea, unconsciousness, and convul-

sions. 3. Sodium restriction leads to greater retention oflithium in the kidney. 4. Diuretics and some NSAIDs reduce lithium excretion and mav cause lithium

toxicity.

Monoamine Oxid nse (IWAO) iahibltors are often usd as third-line Ngents in cases of refractory and atypical depression. Whlch Tiro drugs below are MAO inhlbitors?

. Doxepin (Sinequan)

. Tranylcypromine . lmipr arnine

(P arnate)

(Tofr an i I)

. Phenelzine (Nerdil)

54 Coplright O

20ll-201?

Denral Decks

The vasoconstrietor epinephrins in local anesthetic injections must be used cautiously in patients taking all ofthe following antidepressant drugs EXCEPT one in qrder to avoid transient and signilicant increases in blood pressure. Which one is the ,EXCEPTIOM

. Tncyclic antidepressants (i.e., Elavil)

. .

Selective serotonin reuptake inhibitors (i.e., Prozac and Paxil) Serotonin and norepinephrine reuptake inhibitors (i.e., Effexor and Cynbalta)

Cop)rightO 20ll-2012 - Dnbl Decks

MAO inhibitors are used are often used as third-line agents in cases ofrefractory and atypical depression. MAO inhibitors antagonize the action of monoamine oxidase (MAO) reepinephrine, sponsible for the degradation of the naturally occurring monoamines norepinephrine, dopamine, and serotonin. It is theorized that the increased level of monoamines in the brain is responsible for the antidepressant effect ofthe MAO inhibitors.
Note: Local anesthetics containing epinephrine are genemlly contraindicated in patients who are taking MAO inhibiton.
The major limitation for the widespread use of the MAO inhibitom for the treatment of depression has been the potential for serious adverse side effects, including hypertensive crisis. rvhich can be fatal. A hypertensive crisis can occur within several hours after ingestion of a substance that contains tyramine. Tyramine releases norepinephrine and other sympathonrimetic amines, thereby raising blood pressure. Early symptoms include occipital headache, palpitations, stiff neck, nausea, vomiting, and sweating. Among the drugs that interact with \1AO inhibitors are meperidine (Demerol), epinephrine and ephedrine.

l. Miscelianeous antidepressants include:

\ot

. Bupropion (Wellbrr'tu
hibitor

. Mirtazapine (Remeron): alphaz -noradrenergic antagonnist ,SZ/: norepinephrine / dopamine rer.rptake inhibitor

. Trazodone (Desl,rel): mechanism not clear; possible serotonin reuptake in-

These trvo categories (tt'iclclic qntidepressants snd serotonin and norepinephrine teuprake inhihitors) of antidepressant drugs significantly increas norepinephrine levels in tissues. ln rhe presence of a vasoconstrictor administered via a local anesthetic injection, the patient could experience significant elevation of blood pressure due to the vasopressor actions of the combination. The selective serotonin reuptake inhibitors fi.e., Prozac and Paxil) have no such effect on norepinephrine in tissues and interaction with a vasoconstrictor like epinephrine is not an issue.

\ote:

. Tricyclic antidepressants (i.e., Elavil)

. Selective serotonin reuptake inhibitors (i.e., Prozac and Paxil) . Serotonin

and norepinephrine reuptake inhibitors (i.e., Effexor and Cymbalta)

. Monoamine oxidase inhibitors (i.e., Nardil)

56 Coplright
@

201l-2012 - Denhl Decks

. Yenlafaxine (Effexot) .
N orntpryLine (P am
e

lor)

. Desrpramne (N o rprami n)

. Desvenlafaxine (Prrsfiq) . Sertraline (Zoloft) . Duloxetine

(Cym
b a I t a)

57 Cop)righl O 201| -2012 - Dntal Decks

These two categories ofantidepressant drugs induce significant dry mouth in:up to 75yo ofpatienls taking these medications. These effects are due to the secondary anticholinergic nature ofthese agents. Note: Drug-induced dry mouth must be treated palliatively

with artificial salivary substitutes.

The seldctive serotonin reuptake inhibitors (i.e., Prozac, Paxil) and monoamine oxidase inhibitors have no secondary anticholinergic effects and therefore do not cause any significant dry mouth.

Five major categories of antidepressant drugs: . Tricvclic antideprssants: . Amitriptyline (E/avll)

. Doxeprn (Sinequan)
. Imipramine (Tof'anil)

. Serotonin and norepinephrine reuptake inhibitors: . Yenlafa:.l.ine (Elfexor) . Desvenlafaxine (Pristiq) . Nortriptyline (Pamelor) . Duloxetine (Cymbalta) . Desipramine (Norpramin) . Slective serotonin reuptake inhibitors: . Citaloqam (Celexa) . Paroxerine (Paxil) . Escitalopram (Lexapro) . Sertraline (Zoloft)
. Fluoxetine (Prozac)

. Second generation miscellaneous:

. . . .
Bupropror. (Wel I butrin) Trazodone (Desyrel) Nefazodone (Serzone) Mirtazrpine (Remero n)

. Monoamine oxidase inhibitors: . Phenelzine Q'{ardil) . Tranylcypromine (P arn at e) . Isocarboxazide (Marylan)

. Diphenhydramin

HCL (Benadryl)
maleate (Chlor-Trimeton)

. Chlorpheniramine

. Cimetidine (Tagamet)

. Loratadine (Clantin) . Desloratadine

(C lari n ex)

58 Coplrighr C2011,2012 - Debial Decks

. Prostatitis

. GERD (heartburn)
. Toxic-shock slndrome

. Renal failure

59

CoplrighrO20ll-2012

- Dental Decks

***

Cimetidine is an antihistamine H2-receptor blocker.

Antihistamines are antagonizing agents that compete for receptor sites with natuml histamine, which is stored preformed in cyoplasmic granules of tissue mast cells and blood basophils. It is released in response to lgB-mediated (immediate) allergic reactions and plays an important role in hay fever, urticaria and angioneurotic edema. Note: Histamine also plays an important role in the control ofacid secxetior] (HCL) in the stomach.
There are two t)?es of histamine receptors, H1-receptors, which play an extremely important role in allergic reactions and H2-receptors, which are important in gastric acid secretion. The antihistamines are divided into H,and H2-receptor blockers depending on the histamine receptor they compete for. H1 receptor blockers include:
1.

First-generation (classical) agetts: . Diphenhydramine HCL (Benadryl) and chlorpheniramine maleate (Chlor-Trimetron) *** These agents have a broad spectrurn of action which includes antihistaminic, anticholinergic, antiserotonergic, antibradykinin and sdative propefiies. Second-generation agents:

l.

. CetiiztneHCL Qfrlec), fexofenadine HCL (Allegra),lorctadine (Claritin)

and deslo-

ratadne (Clarinex) *"* Most ofthese agents, because oftheir poor CNS penetratjon (do not ctoss the bloodhrain barrier). cause less sedation and drowsiness than the first-generation agents.
the release of histamine but rather compete with free histamine for binding at Hl-receptor sites. ln general, the binding is competitive. however, some second-generation agents bind non-competitively at higher doses. Common side effects include drowsiness, dizziness, anticholinergic effects /dry moutlt, ose and thrcat), and nausea. They can both stimulate and depress the CNS.

lmportant points: All ofthe H,-receptor blocke$ do not preYent

H2-receptor antagonists compete with histamine at the H2-receptor. Histamine produces ofphysiologic actions in many tissues. While H2-receptors are located in the GI tract and in vascular and bronchial smooth muscle, H2-receptor antagonists compete * ith histamine only in the GI tract. Inhibition of histamine at the parietal cell interteres u ith one of several mediators for signaling the parietal cell to secrete acid.
a s ide variety

H'-bfockers incfude: cin.retidine (Iaga met), ranrtrdrne (Zantac), famotidlne (Pepcitl) and ntzatidire (Axicl).These agents are all revrsible competitive antagonists ofthe actions of histamine on H,-receptors. These agents are used to treat acid-peptic disease, espeand occasionally gastric peptic ulcers. These drugs are also used to treat Zollinger-Ellison syndrome (a hypersecretory disease) and gastroesophageal reflux

cialll duodenal ulcers

disease /GERDJ.

Note: Cimetidine has an antiandrogen effect (can lead to impotence, Ioss oJ libido, and gtnomastia).It also inhibits liver metabolism which can lead to an increase in activity ofother drugs such as warfarin and carbamazepine.

. Hl-receptor site

. H2-receptor site

60
Copyright O

20ll-2012,

Denial Decks

. Cephalexin

. Cephradine . Amoxicillin
. Tetracycline

6l
Coplrighr O 201 l -20
1?

, Dertal Dech

Antihistamines are antagonizing agents that compete for receptor sites with natural histamine. The two types of histamine antagonists are: H1-receptor antagonists: competitively block H1-receptors blocking the effects of histamine at these receptors. They block the vasodilation, they block the constriction ofthe bronchi and they block capillary permeability which histamine ordinarily causes. The blockade ofthese effects of histamine overcomes the svmDtoms of seasonal allergies.

l.

. Actions of Hl antihistamines: - Blocks pain and itch, vasodilation and bronchoconstriction due to histamine - Reduces motion sickress: first-generation only (i.e., Diphenhydramine HCL anrl c h I orpheniramine maleate)
- Promotes sleep: first-generation only

Remember: The second generation Ht-receptor antagonists have the following characteristics: Longer halfJives than first generation (l2-24 hours as opposed to 3-6 hours for first generation), they do not cross the blood-brain barrieq they produce little or no sedation. and have a higher risk of cardiac arrhythmias (long QT ellbct). Examples include Cetirizine HCL (Zyrtec), fexofenadine HCL (AIIegra),loratadine (Cla tin) and desloraradine (Clarinex).

H2-rceptor antagonists: competitively block H2-receptors, blocking the effects of histamine at these receptors. Examples ofthese drugs include: cimetidine (Tagamet), tidine (Zontac), famottdine (Pepckl) and nrzatrdine (Axrd). They block secretion of stomach acid and are used in the treatment ofduodenal ulcers.

:.

\ote:

Histamine is found in all tissues, particularly in mast cells and blood basophils. It is released in allergic and inflammatory reactions.

From the "Advisory Statement, Antibiotic Prophylaxis for Dental Patients with Total Joint Replace)nent" published by the American Dental Association and the American Academy' ofOnhopedic Surgeons, in the J Amer Dent Assoc 1997; 128(7):1004-8 and J Amer Dent Assoc 2003;134:895-898 cephalexin, or cephradine or amoxicillin can be -either used as the drugs ofchoice lor standard prophylaxis medication in the patient with a total

joint replacement.

. Cephalexin (Keflex) is a lst generation cephalosporin; prophylaxis orally I hour prior to the dental procedure.

dose is 2 grams

. Cephradine (Velose, is a lst generation cephalosporin; prophylaxis dose is 2 grams orally t hour prior to the dental procedure.
. Amoxicillin is a mernber of the penicillin family; prophylaxis dose is 2 grams orally t hour prior to the dental procedure.

\ote:

For patients not allergic to penicillin and unable to take oral medications the f4 lst generation cephalosporin) or ampicillin (member of the penicillin family). The regimen is as follows:
suggested medications are cefazolin

. Cefazofin (Ancefl 1 gor ampicillin 2 g intramuscularly or intravenously t hour prior

to the dental Drocedure

. Affects cell membrane

. Interferes with protein synthesis

. Affects cell wall

. Interferes with normal biosynthetic pathways

62

CopyrSh O

201 I -20 12 - Denral Decks

Mefloquine fzanlum) belongs to a chss of drugs which is useful in treating which ofthe following conditions?

,,

. Valaria
. AIDS

. Hepatitis

. Cancer
. Chlamydia

63
Cop)righl O 20ll -2012 - Dental Deks

Mechanisms of action ofantibiotics on the bacteria cell:

. Agents affecting cell wall: -

Penicillins Bacitracin

Vancomycin

- Lnipenem

Cephalosporins - Cycloserine
- Aztreonam

. Agents interfering with protein synthesis:

- Tetracycline - Erythromycin - Azithromycin - Aminoglycosides - Lincomycin - Clarithromycin - Ch loramphenicol - Clindamycin

. Agents interfering with normal biosynthetic pathways:

- Sulfonamides
- Trimethoprim

- Fluoroquinolones (i.e., ciproJloxacin, norJloxacin, Ievo;floxacin, moxiJloxac'in, and

gentilloxacin)

\ote:
*

The most corruron clinical cause of bacterial resistanc is the use of antibiotics

hen they are not indicated.

\'falaria is a devastating parasitic disease transmitted through the bite ofinfected Anopheles mosquitoes. Endemic to tropical and subtropical areas ofAsia, North and South America. the Middle East, North Africa, and the South Pacific. Plasmodium vivax is the most common of four human malaria species (P falciparum, malariae, ovale, and vivax). P. r ir ax causes up to 65% of malaria in India and is becoming increasingly resistant to malaria drugs. By contrast, P falciparum is the most deadly species and the subject of most malaria-related research and literature.

\fefloquine (Lariam)
four malaria species.

has been shown to be effective in treating malaria caused by all

Other antimalarial drugs are:

. Chloroquin (Aralen) . Combination ofatovaquone

. Halofantrine

and proguanil (Malarone)

. Quinine

. Conrbination of sulfadoxine and pyrirnethamine (Fansidar)

. Penicillin

\fK

. Cefaclor (Ceclor)
. Penicillin G . Erythromycin

64 Coplrighl C
201

1,2012 - Dental Decks

Tetracyclines ore the drugs of lirst choice in the treatment ofall of the lollowing EXCEPT one. Which one is the EXCEPTIOM

. \{ycoplasma pneumonia . Chlamydia infections

. Rickettsial infections

Staphylococcal infections

55
Coplright O
201

I 2012,

Dental Decks

Cefaclor is a member ofthe cephalosporin family ofantibiotics. The cephalosporins are penicillin-like in action against bacteria. They are bactericidal antibiotics and act like the penicillins and interfere with cell wall synihesis through inhibition of the synthesis of the peptidoglycan in the cell wall. The antibiotic binds to the enzymes fi. e., transpeptidase) that build/maintain the cell wall. This makes the cell wall osmotically unstable. Bacteda eventually lyse, resulting in death ofthe cell. Cephalosporins act against a wide range ofgram-positive and gram-negative bacteda.

Cunently there are four generations of cephalosporins. Each newer generation has significantly greater gram-negative antimicrobial properties than the preceding one, and a decreased maximum acti\ ity against gram-positive organisms.
Important cphalosporins within each generation:

. First: cephalexin (Keflex), cephradine (Velosqf, cefadroxrl (Duncefl, cefazoin (AnceJ). Most active against S. aureus, Group A Beta-hemolytic streptococci, and Pneumococcus. . Second: cefaclor (Ceclor), cefuroxime (Ceftin), cefoxrtin (Mefoxn), cefprozrl (Cefzil), cefpodoxime /Zartlr). Still have eJficacy against gnm-postivie organisms but also possess good activity against E. coli and H. influenzae. . Third: cefixime (Suprax), cefoperazoqe (Cefobid), ceftriaxone (Rocephir. Have the
broadest spectrum

ofactivity ofall cephalosporins

and are extremely effective against gram-

negati\e organisms. They are more active against E. coli, Klebsiella pneumoniae, Enteroh:rcrer. Salmonella. and Shigella. . Fourth: cefeprme (Maxipime). Effective against Pseudomas aeruginosa.

\ote: Approximately 107o of individuals expressing allergy to the penicillin family antibiotics will have cross allergenicity to the cephalosporins.
aeents. the carbaDenems and the monobactams.

of

Remember: Antibiotics containing this betalactam ring are referred to collectively as betalactam antibiotics and include the penicillins, cephalospodns, and the two newer groups of

Popular Tetracyclines include:

. Tetracycline: used to treat acne, gonorrhea and syphilis in patients allergic to penicillin. exacerbations of chronic bronchitis, Mycoplasma infections and Chlamydia
infections, and Rickensia infections.

. \Iinocycline (Minocin):

used to treat acne, anthrax and meningococcal prophylaxis.

. Dox) clclin (Vibramycin)| used to treat infections caused by Rickettsia, Chlamydia and \{ycoplasma; altemative to mefloquine for malaria prophylaxis and treatment of

slphilis.

. Macrolide class ofartibiotics . Cephalosporin class of antibiotics . Quinolone class ofantibiotics

. Glycopeptide

class of antibiotics

66 CopriShr C 20ll-2012

- Dental

Deck

. CNS effects . GI effects

. Hematologic effects

. Renal effects

Copyrighr

201 1,201 2 - Dertat Decks

Azithromycin (Z-Pak, Zithromax) and clarithrornycin (Biaxin) are members of the macrolide class ofantibiotics in which erythromycin is the prototype agent,
The bacterial spectrums ofactivity ofLzithromycin and clarithromycin are similar to that

of erythromycin but possess greater intrinsic activity against H. influenzae and Helicobacter pylori. These two macrolides concentrate within macrophages, making them
useful against organisms that are taken up by macrophages such as Mycobacterium avium

intracellulare. The significant tissue penetration ofboth agents and the prolonged elimination half-life of azithromycin (l l -14 hours) allows for once-daily dosing for azithromycin and twicedaily dosing for clarithromycin. Note: Macrolide antibiotics are generally used to treat infections caused by streptococcal bacteria and respiratory infections generally. They are also active against syphilis, Lyme disease and leprosy and tuberculosis. The macrolides can have a toxic effect on the liver, causing liver toxicity andjaundice and so should not be given to people who have an underlying liver problem such as an infection with hepatitis C.

\facrolides are bacteriostatic. The mechanism of action involves inhibition of protein

s! nthesis that results from binding specifically to the 50s ribosomal subunit. This causes the Rr\A to dissociate from the ribosome and prevents protein synthesis.

Remember: Intrinsic activity is

it-v.

a measure

ofthe ability ofa drug once bound to the re-

ceptor to generate an effect activating stimulus and producing a change in cellular activ-

Adverse Gl effects are reported for approximately 2lo% ofpatients receiving er)thromycin. about 107o ofpatients receiving clarithromycin, and less than 504 for azithromycin.

In general, oral bioavailability of erythromycin is poor. It is readily inactivated by stomach acid, and several salts have been developed to overcome this drawback.

. Erylhomycin stearate (E4tthrocin)

. Erylhromycin ethylsuccinate

ft.t

S.)

Since they are destroyed by stomach acid, erythromycins are usually entedc coated. This is a term designating a special coating applied to tablets or capsules which prevents their release and absorption oftheir contents until they reach the intestines

**"

\ot: Er,,lhromycin

is metabolized in the liveq excretion is mainly via the bile

. Neomycin

. Streptomycin . Tobramycin . Gentamicin

68 Copyright O 201 I -20 12 , Dentat Deck!

. Penicillins

. Erytfuomycins . Acetylsalicyclic acid (Aspirin)

. Para-aminobenzoic acid (PABA)

Copright

69 201l-2012 - Dental Deckj

Aminoglycosides are potent bactericidal antibiotics that act by creating iissures in the outcr membrane of the bacterial cell. They are particularly active against aerobic, gram-negative bacteria and act synergistically against certain gram-positive organisms. Gentamicin is the most commonly used aminoglycoside, but amikacin may be particularly effective against resistant organisms. Aminoglycosides are used in the treatmcnt of severe infections of the abdomen and urinary tract, as well as bacteremia and endocarditis. They are also used for prophylaxis, especially against endocarditis. Resistance is rare but increasing in frequency. Avoiding prolonged use, volume depletion and concomitant administration of other potentially ncphrotoxic agents decrcases the risk of toxicity. Single daily dosing of aminoglycosides is possible because of their rapid concentration-dependent killing and post-antibiotic effect and has the potcntial for decreased toxicity. Aminoglycosides: . Gentamicin (Garamycit), Amikacin (Aniken), and"tobramycin (Nebci ). These are effective against serious infections caused by aerobic gram-negative bacteria, including E. Coli, Enterobacter, Klebsiella, Proteus, Pseuodomonas aeruginosa, and Serratia. . Streptomycin: The first aminoglycosidc and q,as shown to be effcctive in the treatment oftuberculosis. ls seldon used today. . \eom]cin (Myi/iadn, and Kanamycin (Ka trer)i Due to its toxic potential ncomycin is used only topically or locally /e.g, in the GI tract). Kanamycin is rarely used bccause of its marked lendency to cause ototoxicity.

\ot6 -

because

l. Aminoglycosides may cause severe neuromuscular weakness lasling hours to days oftheir potential curarelike effect. Aminoglycosides may aggravate muscle

rvcakness in patients with muscular disorders such as myasthenia gravis, infant botulism, or parkinsonism. 2. Aminoglycosidcs bind incvcrsibly to thc 30s ribosomal subunit of bacteria, subse-

quently inhibiting protein synthesis. 3. Two wcll-known adve$e effects are ototoxicity and nephrotoxicity.

Sulfonamides are often referred to as "sulfa drugs" because their molecules contain sulfur atoms. They have a different antibacterial mechanism from that ofthe antibiotics. The sullbnamides are structurally similar to PABA and this similarity is the basis for their antibacterial actions. PABA is needed by bacteria for the synthesis of folic acid. In tum, lblic acid is needed for the synthesis of cellular components within the bacteria to allow for cell growth. Because of structural similarities between sulfonamides and PABA, the sulfonamides compete with PABA and are able to inhibit the actions of PABA. With PABA inhibited, folc acid is not synthesized within the bacteria, and bacterial cellular growth is inhibited. Sulfonamides are predominantly bacteriostatic agents.

Examples of sulfonamides: Sulfacetamide, Sulfadiazine, Sulfadoxine, Suliamethizole, Sulfamethoxazole, Sulfanilamide, Sulfasalazine, and Sulfisoxazole.
1. Sulfonamides are not used for treatment of dental infections because ofa low degree of effectiveness against oral pathogens. ,,Note*:.. ',.,1::;:r,:,:: 2 Sulfonamides are used in medicine primarily for the treatment of urinary

tract infections. 3. Bactrim is the brand name for the combination of trimethoprim and sulfamethoxazole. It is considered the drug of choice for many urinary tract infections. Bacteria susceptible to Bactrim include E. coli, Pneumocystis carinii. Klebsiella pneumoniae, Haemophilus influenzae and Salmonella species 4. The trimethoprim component is an antimicrobial and the sulfamethoxazole
is one ofthe sulfonamides. 5. Hypersensitivity reactions ate common. Although blood dyscrasias are relatively rare, they can be fatal.

. Penicillin VK . Erythromycin

. .

Cephalexin (Keflex) Clindamy cin ( C I e o c i n)

. Vancomycin

70 Coplright O 20ll'2012 - Dmral Decks

. Penicillin

. Tetracycline
. Chloramphenicol . Doxycycline

71

Copyn8hi O 201 I -20

12 -

Dental Deck.

Clindamycin binds to the 50s ribosomal subunit, blocking bacterial protein synthesis. Its use is restricted by its side effects such as severe diarrhea and pseudomembranous colitis. These side effects are caused bv the oversrowth of the bacterium known as

Clostridium difficile.
Clindamycin is bacteriostatic and is active against most gram-positive (i.e., Streplococcus pneumonioe, viridans, antl pyogenes as v'ell qs Staph),lococcus aureus) and many anaerobic organisms, including the anaerobic gram-negative bacteria Bacteroides frag-

ilis. In dentistry, clindamycin is an alternate antibiotic in the following situations: . When an.roxicillin cannot be used for the standard regimen for prevention of bacterial endocarditis in patients undergoing dental procedures . For treatment ofcommon oral-facial infections caused by aerobic gram-positive cocci
and susceptible anaerobes . For prophylaxis for dental patients with totaljoint replacement

Important: Clindamycin can be given to patients allergic to penicillins since there is no cross allrgenicity between penicillins and clindamycin.

\ote: \bncomycin

is given IV and is used most often in serious or life-threatening

staph)lococcal or streptoccocal infections. It remains the drug ofchoice for severe cases

ofClostridium difficile. Adverse effects include ototoxicity which may be pemanent and the "red man" syndrome which is characterized by a sudden and profound fall in blood pressure with or without a maculopapular rash over the face, neck, upper chest, and exEemlnes.

Chlorarnphenicol is a broad-spectrum antibiotic effective against gram-positive and eram-neqative bacteria and against anaerobes. It is used as a second or third line drug in medicine to treat serious infections due to organisms resistant to other less toxic antibiotics. For example it can be used to treat the following: Typhoid Fever, Bacterial Meningitis. Anaerobic Infections, Rickettsial Diseases, and Brucellosis. Chlorarnphenicol inhibits protein synthesis in bacteria and, to a lesser extent, in eukaryoric cells. The drug readily penetrates bacterial cells, probably by facilitated diffusion. Chlorar.nphenicol acts primarily by binding reversibly to the 50s ribosomal subunit.
The most important adverse effect of chloramphenicol is on the bone marow Chloramphenicol affects the hematopoietic system in two ways:
response manifested by aplastic anemia, leading in many cases to fatal pancytopenia . by a dose-related toxic effect that presents as anemia, leukopenia, or thrombocytopenla

. by an non-dose-related idiosyncratic

Important: The risk of aplastic anemia does not contraindicate the use of chloramphenicol in situations in which it is necessary; however, it emphasizes that the drug should never be employed in undefined situations or in diseases readily, safely, and effectively treatable with other antimicrobial agents.

Note: Fatal chloramphenicol toxicity may develop in neonates, especially premature babies" when they are exposed to excessive doses of the drug. The illness, the gray baby
syndrome, usually begins 2 to 9 days after treatment is started.

Nitazoxanide fllirro,) is an oral antiprotozosl agnt usd to treat which of th following conditions?

. Leprosy
. Malaria . AIDS . Dianhea caused by Clostridium diflicile . Dianhea caused by Giardia lamblia

72 CoplriShr O

20ll-2012

Dental Decls

.Isoniazid

. Streptomycin
. fufampin

. Ethambutol
. Pyrazinamide

73
cop)'righr

201

l-2012 - Dental Decks

This type of diarrhea is an intestinal infection also known as Giardiasis, and is the most common protozoan infection in the United States.

***

Antiprotozoal Agents:

. Nitazoxanide (Alinia): is an antiprotozoal

agent which is used in the treatment of Giardia, and those protozoal infections caused by Cryptosporidium parvr,rm. Its mechanism is to interfere with the electron transfer reaction wilhin the protozoa essential to anaerobic metabolism. , Atol.a'quone (Mepror): is an antiprotozoal agent used to treat Pneumocystitis pnetmonia (PCP) in patients who are intolerant to co-trimoxazole.

carinii

. Eflornithine

(Vaniqa): has orphan drug status for the treatment of meningoencephalitic stage ofTr)?anosoma brucei gambiense tnfection (sleeping srcinesy'. This
drug is also indicated to be used as a cream to reduce unwanted hair from face and ad-

jacent areas under the chin.

(Furoxone)'. is a antiprotozoal agent used to treat dianhea caused by susceptible Giardias lamblia and Vibrio cholerae. . Jletronidazole (Flab-l): is a synthetic antibacterial and antiprotozoal agent that is eflective against Trichomonas vaginalis, which causes trichomoniasis. In addition, it is one ofthe most effective drugs available against anaerobic bacterial infections. These include infections caused by Helicobacter pylori, Clostridium difficile, Bacteroides species and Fusobacterium species. Note: Alcohol should be avoided because metronidazole and alcohol together can cause severe nausea, vomiting, cramps, flushing, and headache. It should is not used in pregnancy because of potential adverse effects on the fetus.

. Furazolidone

Tuberculosis is a bacterial infection caused by Mycobacterium tuberculosis. The antitubercular drugs either inhibit the growth ofthe bacteria or kill the bacteria. Because the \llcobacterium organism tends to develop resistance to any single antitubercular drug, combination drug therapy is standard in the treatment oftuberculosis.

.A.ntitubercular drugs:

. lsoniazid: often given in a four drug regimen along with rifampin, pyrazinamide and
ethambutol

. Streptomycin: often given in combination with isoniazid . Rifampin: usually given in combination with other agents . Ethambutol: usually given in combination with olher agents . Pl razinamide: popular in combination with rifampin
]Iechanism of action: . Isoniazid: is bacteriostatic for resting organisms and bactericidal for dividing organisms. It interferes with lipid and nucleic acid biosynthesis in growing organisms. . Streptomycin: is a bactericidal antibiotic. It acts by interfering with normal protein
s)rlthesis.

DNA-dependent RNA-polymerase activity, thereby supressing RNA synthesis. It can be bacteriostatic or bactericidal and is most active against bacteria undergoing cell division. . Ethambutol: impairs cellular metabolism, causing cessation of cell multiplication and cell death. It is bactericidal and is active only against Mycobacterium. . Pyrazinamide: the mechanism ofaction is unknown. It may be bacteriostatic or bactericidal against M. tuberculosis, depending on the concentration.

. Rifampin: inhibits

. Herpes zoster

. Genital

herpes
1

. Herpes simplex type . Papilloma virus

(HSv-|)

71
Copyrighl O 20ll-2012 - Denhl Deck

. Didanosine

. Zidowdine . Ritonavir . Indinavir

. Delavirdine

Coplrishr O 2011-2012 - Dental Decks

Penciclovir (Denavi is a cream formulation indicated for the treatment of recurrent herpes labialis (cold sores) in adults. This condition is caused by the herpes simplex type
1

virus. Penciclovir is not available for systemic dosing.

Penciclovir (Denavir) inhibits viral action by selectively inhibiting herpes viral DNA synthesis and therefore resulting in the inhibition ofviral replication,
Other agents indicated for use in treating the condition ofherpes labialis are:

. Acyclovir tablets . Acyclovir cream

. Docosanol cream (lbreva) . Lysine tablets . Valacyclovir caplets (Valtrex)

AIDS has been recognized since

l98l

as a unique clinical syndrome brought on by in-

fection with the human immunodeficiency virus | (HIr/-l) or virus 2 (HIV-2).The major cellular defect caused by infection with HIV is a depletion ofT cells, primarily the subqpe T-helper cells kaown as CD4 cells. This results in a compromised immune system, * hich becomes susceptible to opportunistic infections.

HIV is a type ofretrovirus that is responsible for the fatal illness flom AIDS. A retrovirus
nucleic acid and uses the enzyme reverse transcriptase to copy lts genome into the DNA olthe host's cells chtomosomes. This DNA segment is then permanently incorporated into the host cell's DNA within the nucleus. The integrated DNA segment can produce nerv RNA in the cytoplasm of the host cell. The new RNA in tum synthesizes viral proteins, which are eventually passed on to other host cells such as the immune system macrophages. Ultimately enough ofthe human immune cells are compromised such that
has
as its

R\A

immune function is lost.

name Wdex), zidovtldine (brand name Retrovil), ritonrvir (brand name Norvry', and indinavir @rand name Crixivan) work by inhibiting certain steps in the HIV inlection process within the target cells to halt the destruction of the immune system by the HIV retrovirus. The HIV drugs such as didanosine
@ rand

. Bacitracin . Amphotericin-B
. Polymyxin-B . Neomycin

76
CoplaiSht @ 201l-2012 - Dental Decks

. Penicillin . Erythromycin
. Nystatin

. Chloramphenicol

n
CoP)right
@

201l-2012 - Dntal Decks

This is an antifungal agent given intravenously or orally for the treatment ofsevere systemic fungal infections caused by fungi such as Candida species. Bacitracin, polymyxinB and neomycin are not antifungal agents. These are antibiotics effective against susceptible bacteria. Antibiotics in general do not have antifungal properties.

Candidiasis is an infection, usually ofthe oral cavity or vagina, with a candida species, usually C. albicaDs, which causes an inflammatory, pruritic infection characterized by a thick, white discharge. It is common, especially in patients who have a deficiency in T-ly,rnphocytes, or who are receiving chemotherapy, and in immunosupressed individuals /,4lDSpalie s).Thisyeast-like fungi is a normal inhabitant of the oral cavity and vaginal tract, however it is normally held in check b; the indigenous bacteria ofthese areas. Note: Angular cheilitis Oilateral ulcers at the comer of rhe ntoutht has been linked to C. albicans.

Remember: Nystatin and clotrimazole are the two antifungals that are used as "swish and swal-

fo\r'' to treat oral candida infections. Nystatin (Mycostatin) is taken as an oral suspension to be
sn ished around thc mouth and swallowed. Clotrj.lri.azolc (M))celer, is taken as a troche (lozenge) \\hich is slorvly dissolved in the mouth and swallowed. They work by binding to sterols in the fungal cell rnembrane, increasing permeability and permitting the leakage ofintraccllular componcnts.

This leads to the death ofthe atTected fungal cell.

Note: The suffixes ofthe following generic drug narnes are indicative ofthe conespsonding drug
classes:

. "azole" = azole-type antifungal drugs (e.9., clotrimazole)

. "coxib" = COX-2 inhibitors fe&, celecoxib) . "dipine" = dihydropyridine calcium channel blockers (e.g., nicardipine) . "olol" = beta-adrenergic receptor blockers (e.g., naclolol )
. "onium" or "urium"

. "ilol" or "alol" = beta-adrenergic receptor blocker that also blocks alphal-adrenergic receptors
(e.g., canedilol or labetalol) quatemary ammonium compounds, usually competitive peripheral acting skeletal muscle relaxers (e.9., pancuronium) . "osin" = alphar-adrenergic reccptor blockers (e.g., terazosin) . "pril" - ACE inhibitors (e.g., enalapril) . "sartan": angiotensin II receptor blockerc (e.9., olmesartan) . "statin" = HMG-CoA reductase inhibitor (e.9., atoflastatin)

. Penicillin V

. Penicillin G
. Ampicillin

. Amoxicillin

7a Coptrighr O 20ll-2012, Dnial Decks

. Penicillin VK . Amoxicillin
. Penicillin G . Ampicillin

79
Coplrighr O
201 l

-2012 - Dntal Decks

All penicillins

are derivatives of 6-aminopenicillanic acid and contain a beta-lactam ring structurejoined to a thiazolidine ring. The betalactam ring is essential for its antitracterial activity. This basic structure is synthesized by the penicillium mold from two amino acids, L-cysteine and L-valine. Antibiotics containing this betalactam ring are refered to collectively as beta-lactam antibiotics and include the penicillins, cephalosporins, and the two newer goups ofagents, the carbapenems and the monobactams.

Penicillln G (benzylpenicillin) is the prototype for comparison. By side chain substitutions (speciJically, this means substituting other groups at the R position ofthe penicillin mol' ecule) of thebasic 6-aminopenicillanic acid molecule, the semi-synthetic penicillins are produced which are more acid stable, have a broader spectrum, or are penicillinase resistant.
Other naturally occrming penicillins include: . Penicillin VK (Pen Vee K, V-cillin K) - preferred for treating oral infections because it is more acid stable (more reliable oral absorption) . Penicillin G parentzl (Pfzeryen) - always given by IM route . Penicillin G benz hine (Bicillin C-R) always given by IM route. It is used for the treatment of syphilis and prevention ofrheumatic fever

Remember: L Penicillins are bactericidal; they inhibit cell wall synthesis. 2. Probenecid increases blood levels of natural penicillins and may be given concurrently for this purpose.

Acid stable penicilhns (may be used orally) include: . Penicillin VK . Amoxicillin . Ampicillin . Nafcillin . Oxacillin . Cloxacillin . Dicloxacillin
Extended spectrum penicillins include:

. The aminopenicillins

Ampicillin and Amoxicillin

Broad spectrum penicillins include: . Piperacillin . Ticarcillin

***

These two penicillins have the widest spectrum

ofall the penicillins

Penicillinase-resistant penicillins include:

. Nafcillin . Oxacillin . Cloxacillin . Dicloxacillin

. Penicillin

\{K

. Tetracycline . Erythromycin . Amoxicillin

80 Copltighr C
201

l-2012 - Dental Decks

. Tetracycline
. Clindamycin

. Ampicillin

. Cefaclor (Celcor)
. Penicillin VK

81

Cop)'right O 20ll-2012 - Denral Decks

Premedication requirements for patients with valvular heart disease or congenital cardiac defects. If in doubt, have patient consult their physician as to need.

CurrentAmerican Heart Association Guidelines: Published

page 142.

June 2007, JADA Volume 138,

Standard Regimen
. Amoxicillin - Adults: 2.0 g orally 30-60 minutes prior to appointment - Children: 50 mglkg (not to exceed adult dose) orally 30-60 minutes prior to appointment

Allergy to Amoxicillin: Note: Only ifallergy is not ofanaphylactic type. Any one ofthe following
. Clindamycin -Adults: 600 mg orally 30-60 minutes prior to appointment -Children: 20 mg,&g orally 30-60 minutes prior to appointment

can be used.

'Cephalexin -.\dult.: 2.0 g orally 30-b0 minutes prior to appointment

-Children: 50 mg/kg orally 30-60 minutes pdor to appointment

..{zithromycin
-Adults: 500 mg orally 30-60 minutes prior to appointment -Children: l5 mg/kg orally 30-60 minutes pdor to appointment . Clarithromycin -Adults: 500 mg orally 30-60 minutes prior to apporntment -Children: l5 mg/kg 30-60 minutes pdor to appointment

It is prudent to use an antibiotic with narrow spectrum ofaction and one that is bactericidal in order to minimize the development ofbacterial resistance. Penicillin VK has these properries. Ampicillin has a broader spectrum of action than penicillin VK and cefaclor is a broad spectrum cephalosporin. Tetracycline and clindamycin are bacteriostatic antibiotics and not bacteriocidal.
Note: The major disadvantage of the penicillins is their rather high incidence ofallergic reactions. Approximately l0olo ofthe general population is allergic to penicillins. This incidence probably holds for any ofthe specific penicillins since there is cross allergy from one to the other Skin rash (a delayed reaction) is the most prevalent allergic manifestation. Life threatening anaphylaxis can occur, but is very rare, particularly with oral dosing. In non-allergic individuals, penicillins at normal therapeutic doses have virtually no side effects what so ever Penicillins are bactericidal' that is, they actually cause death of the invading bacteria.

. Penicillin VK

. Dicloxacillin
. Amoxicillin

. Piperacillin

a2

CoDriglt

@ 201

I 2012,

Denral Dects

\-

Which ofthe following has a clinicrly sign icant drug interaction with Amoxicillin?

. Tiazolarn (Hzlcion)

. \4ethotrexate
. Calcitrol

. Candesartan

83
Coplright O 201 I -20
12

- Dental Decks

Members ofthe penicillin family having the broadest spectrums ofaction are piperacillin

and ticarcillin. In addition to being active against gram-positive cocci (streptococci,

staphylococci, pneumococci), and gram-positive rods (bacillus and otfters), these agents are active against Pseudomonas, Proteus, Klebsiella, and Bacteroides These antibiotics are recommended for the treatment of urinary tract infctions and other infections caused by susceptible gram-negative Pseudomonas species and Proteus
specles.

Penicillin VK has a relative limited spectrum of action against aerobic gram-positive

cocci and anaerobes.

Dicloxacillin has a similar spectrum

producing staphylococcus.

as

penicillin VK but is active against penicillinase-

.{moxicillin is an aminopenicillin which has an extended spectrum ofaction which includes not only aerobic gram-positive cocci and anaerobes, but some gram-negative bacilli such as Hemophilus, Proteus and Salmonella. Ampicillin also falls into the category of an aminopenicillin. Important: None ofthe penicillins are aclive against viruses, fungi, rickettsiae or other
nonbacterial orsanisms.

*** Amoxicillin in large

doses

inhibits the renal tubular secretion of methotrexate,

thereby causing higher, prolonged serum levels ofmethotrexate.

Aminopenicillins (enpicillin and amoxicillin) are characterized by the amino substitution ofpenicillin G. They are able to penetrate gram-negative bacteria more readily than are the natural penicillins or the penicillinase-resistant penicillins. However, the aminopenicillins are not stable to beta -llct^ma;ses (penicillinase) of either gram-positive
or gram-negative bacteria.

Note: Gram-negative bacteria that are susceptible to aminopenicillins include: H.influenzae, some E.Coli and Proteus mirabilis.

Ampicilf in (Pol1,cillin, Onipen) and Amoxicillin (Amoxil, Larotid)

are

ttsedprimarily to

treat infections such as otitis media, bronchitis, sinusitis, and acute bacterial cystitis caused by susceptible organisms. Compared with ampicillin, amoxicillin has a higher oral absorption, higher serum levels, a longer halflife, and is less likely to cause adverse GI ef-

lects (diarrhea). Amoxicillin is given orally; ampicillin can be given orally or IV. )rlote: Ampicillin and amoxicillin are preferred agents in the treatment ofurinary tract infections caused by susceptible enterococci (which are facultatively anaerobic, grampositive cocci that grow in short chains under extreme conditions mainllt in the intestine).

. Amoxicillin and clalulanate potassium (Augmentin) . Ampicillin and sulbactam (Unasyn) . Cloxacillin . Dicloxacillin

84
Coplright O 2011,2012 , Denbl Decks

Which of the followlng bacterial enzymes

belong to the

fanily of beta-lactamases?

. Cephalosporinase
. Penicillinase

. AT?ase
. Protein kinase

coplnshr O 20ll-2012

- Dental Declc

A functional part ofthe chemical molecule of all the penicillins is the so-called betalactam ring, which is a four-membered imbedded ring structure consisting ofthree carbons and one nitrogen atom which is responsible for the antibacterial activity of penicillins. Any alteration to the beta-lactam ring will also alter the antibacterial activity. Penicillinase is an enzyme secreted by bacteria which splits open the betalactam ring. This renders the penicillin molecule ineffective against those penicillinase secretors.

Cloxacillin and dicloxacillin resist the actions ofpenicillinase because they have tected beta-lactam ring which prevents the actions ofthe enzyme.

pro-

Augmentin and Unasyn contain the agents clavulanate potassium and sulbactam respectively which block the actions ofpenicillinase from reaching the betalactam ring.
The majority ofpenicillins are directly excreted into the urine through renal tubular cell secretion. Probenecid (Benemid), an inhibitor of renal tubular cell secretion raises the blood ler els ofthe penicillins by diminishing their tubular secretion. Probenecid is sometimes given simultaneously with penicillin to raise the blood levels for increased activirr. \ote: Probenecid is a drug used to treat gout.

Beta-lactamases are nzymes produced and secreted by a wide range of gram-positive and gram-negative bacteria as a defense weapon against cephalosporin and penicillin antibiotics. These enzymes destroy the beta-lactam nucleus within these antibiotics by splitting open the betalactam ring structure. This action renders the antibiotic ineffectir e. Those beta-lactamases that work against cephalosporins are called cephalosporinases, and those that work against penicillins are called penicillinases.

By combining clavulanic acid with a penicillin, the betalactamase enzyme is pennanently inhibited by the acid, and the antibacterial activity ofthe penicillin is n.raintained. One popular commercial preparation is Augmentin, which contains arnoxicillin and clavulanate potassium. Augmentin is used orally as pill or liquid form. Sulbactam is another beta-lactamase inhibitor lt is available for intravenous and intratnusculat use combined with ampicillin under the brand name Unasyn.

. Imipenem . Probenecid

. Hydrochlorothiazide
. Aztreonam

86
Cop].righl O 2011,201? - Dntal Decks

Whlch antlbiotic is used cautiously du to its side effects @seudomembranous colitis, severe GI upset)?

.\

. Azithromycin (Zithromax: Z-Pak)

. Clindamycin

. Penicillin VK

Cephalexin (Keflex)

a7
Coplrighr o2011,2012 - Dertal Decks

This elevates and prolongs the serum concentrations sue concentrations are necessary.

***

ofthe antibiotic when high tis-

The majority ofpenicillins are handled by the kidneys as organic acids and excreted by tubular excretion. Probenecid interferes with tubular handling of organic acids within the nephron. Drugs affected by probenecid include most cephalosporins and natural penicillins, and other betalactam-related antibiotics such as aztreonam and imipenem.

Note: In some

cases, probenecid administration can more than double the serum concentration olthe affected drug. The halflife is prolonged as well.

lmportant: Nafcillin, oxacillin, cloxacillin and dicloxacillin are lipophilic and are excreted by biliary means. No combination with probenecid or dosage adjustment for renal
dy'slunction is necessary for these penicillins. is a beta-lactam antibiotic derived from thienamycin and is the first drug to be classified as a carbapenem antibiotic. It is curently the drug of choice for infections due to Enterobacter and Pseudomonas aeruginosa' It is usually combined with cilastatin and is used to treat severe or reslsta.nt lnfections, especially those that are nosocomial in origin. 2. Aztreonam is a parenteral synthetic betalactam antibiotic (classified as a monobactum). The spectrum is limited to aerobic gram-negative rods (i.e., Kebsiella, Pseuclonlonqs, and Serratia).Ithas no gram-positive or anaerobic activity. lt is synergistic with aminoglycosides.

\ot

l. Imipenem

Penicillins:
Penicillin VK

Amoxicillin .{moxicillin,Clav. Acid /lugnrtrr)

AmpiciUin

Cephrlosporins:

(Xher:

Cephalexin /Ke./i".r/ C.faclor (Ceclor) Clindamycin

Inhibits cell wall synthesis

Same

Inhibits 50S ribosomes

Tetracyclines:

Telcycline
D oTyxy clir'e ( Yi brary c in

Minocy.llne (Miioc

itl : Ares tin)

lnhibits DNA lnhibits cell wall synthesis Inhibits 50S nbosomes

Which antibiotic/antimicrobial is associrted with the highest incidenc ofdrug allergy?

. Crprofloxacin (Cipro)
. Penicillin VK . Clindamycin . Mefi oridazole (F I ag! l)

88 Coplright O 201

I 2012,

Denlal Decls

Stavudine (a/so fz own as d4T, or Zerit) is an antiretroviral drug used in the treatment of adults with HIV infection in combination

with other antiretroviral agents. Which ofthe following categorles does this agent blong to?

. Nucleoside reverse transcriptase inhibitor . Protease inhibitor . Non-nucleoside reverse transcriptase inhibitor

89
Copyrighr O 201 l'2012 - Dental Decks

Three groups

ofallergic reactions to the penicillins: (anaphylactic shock): occurs within 30 minutes. Characterized by urticaria, angioedema, bronchoconstriction, GI disturbances, and shock. Death can result in a short time if treatment is not instituted immediately (parenteral administration of

l. Actte

epinephrine).
2. Accelerated: occus 30 to 48 hours after. Manifestations include urticaria, pruritis, wheezing, mild laryngeal edema, and local inflammatory reactions. Not life threaten-

ing' 3. Delayed: occurs after 2 to 3 days. Approximately 80-90% ofall allergic reactions occurring with penicillin are ofthis t1pe. Manifested by skin rashes. Hypersensitivity reactions occur in up to l07o ofpatients receiving penicillin. Manifestations range from a mild rash to anaphylaxis. The rash may be urticarial, vesicular, bullous, or maculopapular. Rarely, thrombopenic purpura develops.

lllote: A rash is the most common sign olan allergy to penicillin.

Rmember: The mechanism ofaction ofthe fluoroquinolones is inhibition of DNA gyrase, an enzyme that is essential in the transcription, replication, and repair ofbacterial D\.{. Drugs in this class include ciprofloxacin (Cipro), norfloxacin Qtloroxin),levofloxacin (Levaquin), moxifloxacin (Avelox), and gemifloxacin (Factive). Fluoroquinolones are active against many gram-positive organisms and gram-negative aerobes, including Moraxella catarrhalis, Haemophilus influenzae, E. coli, chlamydia, and Mycoplasma pneumoniae. They are not active against Clostridium difficile. These drugs are rr ell tolerated, howevet the most common adverse effects are Gl (e.g., nausea, vomiting, diqrrheq, abdominal pain),CNS (e.g., headache, clizziness, confusion) and dermalologrc
le.g., rash, pruritis).

These agents chemically are nucleosides and work by inhibiting the viral enzyme known as reverse transcriptase, This results in an inhibition ofthe HIV viral RNA from being

made into a DNA segment; thus the genome ofthe HIV virus is not copied from RNA. Other agents in this class include didanosine (Wdex), zalcitabine (Hivid; ddC) and zidovudine (Ret ovir ; AZT).

Proteas inhibitors suppress viral replication by inhibiting protease' the enzyme responsible for cleaving viral precursor peptides into infective virions. Some agents in this

class include indinavir (Crixivan), nelfinavir (nracept),

ritonavir (Norvir),

and.

saquinivir (lnvirase). \onnucleoside reverse transcriptase inhibitors inhibit the catalytic reaction of reverse transcriptase that is independent ofnucleotide binding. Some agents in this class include delavirdine (Rescriptor), adefovfi (Hepsera) and nevirapine (Wramune).

. Photosensitivity . Nausea

. Bone marrow disturbances

. Diarrhea

. Discoloration ofteeth and enamel hypoplasia in young children

90
Coplright O 2011,2012, Denbl Decks

. Penicillin VK
. .{mpicillin (P o l:tc i I I in)

. Cloxacillin (Cloxapen)

. Amoxrcrlhn (Amoxil)

91

Copyight r 20ll-2012 - Denhl Decks

Another common adverse effect is the occurrence ofopportunistic (superintbction) infections caused by Candida albicans, This is due to the wide spectrum of antibacterial action which alters normal flora. Examples include both vaginal and oral candidiasis. These conditions are also known as vaginal and oral yeast infections.
Members of the tetracycline family ofantibiotics include:

Short acting:

Intermediateacting:
Long

acting:

. Tetracycline (Generic) .Demeclocycline (Declomycin) . Minocycline (Minocin) . Doxycycline (4bramycin)

Remember: The usefulness of the tetracyclines in the treatment of odontogenic infections is limited since they can cause "yeast'' infections very easily. They have been used as alternatives to penicillin in patients with ANUG (acute necrotizing ulcerative gingil lll.r/ u'ho require antibiotics.

\ote: In adults, Fanconi syndrome can be caused by various things that damage the kidne1s. including certain medications (azathioprine, cidolbvir gentamicin, and tetrucyc/ire). Fanconi syndrome is a disorder ofthe kidney tubules in which certain substances normally absorbed into the bloodstream by the kidnevs are released into the urine instead.

These trro antibiotics are characterized by the amino substitution of penicillin G. They \\ ork against many gram-positive organisms and some gram-negative bacteria such as Haemophilus influenzae, some Escherichia coli, and Proteus mirabilis. They are not penicillinase resistant. They are used for upper respiratory infections. The major difference in the drugs is the higher oral absorption, higher serum levels, and longer half-life for amoxicillin compared with ampicillin. Amoxicillin is given orally; ampicillin can be given orally and IV

Remember: Oral amoxicillin is recommended as the drug ofchoice for standard general prophylaxis for bacterial endocarditis in patients undergoing invasive dental procedures. Note: Parenteral ampicillin is recommended as the drug of choice in patients unable to take oral medications and who are not allergic to penicillin for prophylaxis for bacter-

ial

. Affect bacterial cell wall . Affect bacterial DNA . Affect bacterial protein synthesis

. Interfere with bacterial metabolic pathways

92 coplright
@ 201

|-2012 -

al Decks

. Bacterial cell wall destruction . Prevent protein synthesis in the bacterial cell

.Interfere with nucleic acid synthesis

. Cause mutations within bacterial DNA

93
Coplrighr O 201l-2012 - Dental Deck!

Basic mechanisms of actions ofantibiotics:

. Affect bacterial cell wall:
- Penicillin family - Cephalosporin family

. Agents affecting bacterial DNA:

- Fluoroquinolone family (i. e., ciproJloxacin)

- Meronidazole (F lagt l)

. Agents affecting bacterial protein synthesis:

- Tetracycline family

- Erythromycin family - Clindamycin

- Chloramphenicol

. Agents interfering with bacterial metabolic pathways:

- Sulfonamides (sulfa drugs)

The tetracyclines inhibit protein synthesis by binding to the 30 S subunit ofthe bacterial ribosome. The inhibition of this ribosomal function interferes with the attachment of the growing amino acid chain thus preventing complete formation of peptides from the ribosome. Since no peptides are formed, no proteins are formed. Since proteins are necessary for the bacterial cell to metabolically function, the lack thereof will cause a static state in which the bacterium becomes nrlnerable to phagocltosis by the body's imrnune
S-v"SIem.

Absorption of the tetracyclines from the GI tract is inhibited by divalent and trivalent cations such as CA--, Mg.-, Fe-., and Al**.. These ions form chelation products with the tetracyclines and thus prevent their absorption. This is why tetracyclines should not be given with milk and dairy products (contain Ca--), iron-containing vitamins (contain .Fet!, mineral supplements containing these irons, or antacids (contain Mg").

. Cephalosporins
. Ampicillin

. Tetracycline
. Penicillin G . Penicillin VK

94
Copyighr C
201

l-2012 - Dental Decks

Erlthromycin is a

antibiotic which binds to the ribosomal subunit of susceptible bacteria, The result is the inhibition of protein rynthesis.

. Bactericidal;
. Bactericidal;

30s
50s

. Bacteriostatic; . Bacteriostatic;

30s 50s

95
Coplrighr O 201 l-2012 - Dertal Decks

The tetracyclines are a goup of broad-spectrum, bacteriostatic antibiotics that inhibit protein synthesis in the susceptible organism by binding to the 30S ribosome subunit, thereby impeding the binding of aminoacyl IRNA to the receptor site on the messenger RNA ribosome complex. The inlibition ofthis ribosomal function interferes with the attachment ofthe growing amino acid chain thus preventing complete formation ofpeptides from the ribosome. Since no peptides are formed, no proteins are formed. Since proteins are necessary for the bacterial cell to metabolically function, the lack thereof will cause a static state in which the bacterium becomes vulnerable to phagocytosis by the body's immune system.

Ttracyclines are useful in treating the following infections: . Medical infections caused by susceptible gram-positive and gram-negative bacteria . Infections caused by Mycoplasma, Chlamydia , Protozoa or Rickettsia . Exacerbations of chronic bronchitis . L)ryne disease (caused by Bon'elia burgdorferi)

. Treatment ofacne
. Treatment of gononhea and syphilis in patients allergic to penicillin . Dental: treatment ofperiodontitis associated with the presence of Actinobacillius actinomycetemcomitans (AA) (i.e., Iocalized aggressive periodontitis)

Important: Tetracyclines are not the drug of choice for Streptococcus or Staphylococcus.

Erythromycin-type antibiotics are members of the Macrolide family of antibiotics.

Members of the Macrofide family /generic and brand names) are.

. Azithromycin (Zithromax; Z-Pak) . Cl ar ithr omy cin (B i ax in ) . Erythomycin base (E-mycin; Eryc) . Erythomycin ethylsuccinate lE E S./ . Erythromycin stearate (Etythrocin)

All of

the rythromycins are very effective against gram-positive bacteria but not so effeclive against gram-negative bacteria.

AII ofthe erythromycins act through the same mechanism to bind to the 50s ribosomal subunit ofsusceptible bacteria. This causes the RNA to dissociate from the ribosome and
prevents protein synthesis.

\ote: GI Tract upset

food.1.

is the most common side effect of the erythromycins (tqke with

. Tetracycline . Penicillin VK

. Metr onidazol e (F l a gy l)
. Clindamycin

96

Coplrighi o 201I-20t2 - Ddtal Decks

Acyclovir (Zovirax)

. Oseltamli (Tamillu)
. -{mantadine (Symmetrel)

. fumantadine (Flumadine)

. Zanarnivir

(Relenza)

97
Coplrighr C 20ll-2012 - Dental Deck

The photosensitivity reaction caused by the tetracycline family of antibiotics results in the appearance ofred rashes or blotches over the skin in the presence of sunlight.

Common advrse effects caused by the other agents:

. Penicillin VK: hypersensitivity resulting in skin rash and rare anaphylaxis . Metronidazole (Flagyl): dizziness, headache, and nausea Note: Metronidazole is not a true antibiotic since it is not found in natural organisms; it is a synthetic substance produced in the chemical laboratory.

. Clindamycin: diarrhea, abdominal pain; known to cause pseudomembranous colitis

Oseltamivir (Iarr iflu) and zanrmivir (Relenza) inhibit influenza virus neuraminidase
enz! mes. potentially altering virus particle aggregation and release. Tamiflu and Relenza are both used to treat acute illness due to influenza (A or B) infectior'.

Acyclovir (Zovirax) is an antiviral that inhibits DNA synthesis rather than neuraminidase
enzymes.

Amantadine is a synthetic anti-viral drug that can inhibit the replication of viruses in cells. lt was initially used to prevent influenza A during flu season, and, if given within 24 to 48 hours of the onset of flu symptoms, to decrease the severity of the flu. Later
amantadine was found to cause improvement in the symptoms ofParkinson's disease.

Not: The mechanism of amantadine's antiviral activity involves interference with a viral protein, M2, which is required for the viral particle to become "uncoated" once taken inside a cell by endocytosis.

Rimantadine is a synthetic anti-viral drug that can prevent viruses in cells from multiplying. Like amantadine, rimantadine initially was used to prevent influenzaA during flu season, and, if given within 24 to 48 hours after the onset of flu symptoms, to decrease the severity ofthe flu. Rimantadine is chemically related to arnantadine, but rimantadine
has fewer side effects on the nervous system than amantadine.

Note: Rimantadine appears

to exen its inhibitory effect early in the viral replicative cycle, possibly inhibiting the uncoating ofthe virus (similqr to amantadine s nechanism oJ action).

. Tetracycline
. Doxycycline (Wbramycin)

. Minocycline (Minocin)
. Penicillin VK

98
Coplrighr O
201

1,2012 - Denral Decks

. Laryngeal edema

. Ufiicada (welts that itch) .

Severe hypotension

. GI disturbances
. Bronchoconstrictron (ah'wqy constriction)

Shock

99
Coplright
@ 2Ol

l-2012 - Denral Decks

Penicillin VK is not harmful to the fetus when taken by pregnant mothers. [t is not incorporated into bony tissue or in the teeth ofchildren like the tetracyclines. Note: Tetracycline and all members of the tetracycline family are contraindicated in children up to 8 years old and in pregnant women. Tetracyclines have the ability to chelate calcium ions and become incorporated in the bony tissues. The teeth ofchildren
who have been given the drug may develop a greenish-brown discoloration. This effect is sometimes seen in the newly erupted teeth of infants whose mothers have received tetracycline during pregnancy.

Rmember: Penicillins, which are bactericidal against susceptible organisms, disrupt s) nthesis ofthe bacterial cell wall and compete for and bind to specific enzyme proteins that catalyze transpeptidation and cross-linking. The enzymes to which tbey bind are called penicillin-binding proteins (PBPs). They consist of transpeptidases, transglycosylases. and D-alanine caboxykinases and are implicated in the final phases ofbuilding and reshaping ofthe bacterial cell wall while it is growing and dividing.

**"

This reaction most conmonly occurs with parenteral administration ofpenicillin.

This reaction can be fatal if countermeasures such as the injection ofepinephrine are not taken promptly. Epinephrine prevents the release of substances from mast cells and anlagonizes the actions of histamine and leukotrienes of smooth muscle. The most common adverse effect ofpenicillin therapy is an allergic reaction. These reactions occur in up to 109/o of patients receiving penicillin. The most common manifes-

ration is a mild rash.

Allergic reactions to penicillin are classified into three groups: l. fmmediate onset reactions (araphylaxis) ocatr within 30 minutes; Ig-E mediated.
2.

Accelerated allergic

reactions arise 30 minutes to 48 hours after administration.

Urticaria, pruritis, wheezing, and local inflammatory reactions. In general, not lifethreatening.

allergic reactions take longer than two days to develop. 80-90% ofpenicillin reactions are ofthis type. Basic skin rashes, which are generally mild.
3. Delayed

The phenothiaz ines

. The thioxanthenes

. The butyrophenones . The benzodiazepines

100 Coptrighr O 2011,2012 - Dental Dsks

All of tbe following are phenothiazi nes EXCEPT oae. which one is the cXcrPZolv?

. Chlorpromazine (Thorazine) . Halopeidol (Haldol)

. Prochlorperazine (C omp azin e)

. Thioridazine
r De-h--"-i--

. Trifl uoperazine

(St e laz ine)

t0'l
Coplrlgh O
201 I -20 12

- Denbl Decks

Antipsychotics, also known as major tranquilizcrs orneuroleptics, are used commonly in the treatmcnt of a variety ofpsychotic disorders. By fa. the most widely used group ofantipsychotic agents uscd in medicine are the phenothiazines, followed by the butyrophenones and the thioxanthenes.
The first antipsychotic on thc markct, chlorpromazine, is the key drug among the phenothiazine antipsychotic agents. Currently, antipsychotics are divided into two gcncrations. The first generation includes thc older, "typical" drugs that treat the positive but not the negative symptoms associated with a psychotic state. Second-generation drugs have far fewer extrapyramidal symptoms fEPt and tardive dyskinesia fDJ, and they are used to treat both positive and negative symptoms ofschizophrenia. Note: With the exception ofrispcridone, thy are prolactin sparing. The exact mechanism of antipsychotic drug action is unknown. These drugs are thought to work by blocking postsynaptic dopamine receptors in the h,?othalamus, basal ganglia, limbic system, bminstem, and medulla, and to some extent serotonin receptors-

Typicaf antipsychotic drrgs (frst generationJ are more potent antagonists ofD2 dopamine receptors than ofDr receptors. First generation drugs include the phenothiazines (chlorpromazine, fluphenazine, perphena:ine, procltlorperazine, trifluoperazine, mesoridazine, and thioidazine), the thioxanthines
(

thiothixene) and the btrytophenor\es (haloperidol).

(second generallor/ or atypical antipsychotic agents affcct different receptor sites compared generation antipsychotics. They bind dopamine, including D1, D2, Da, and D5 receptors, with selecrilely lor limbic dopaminc rcceptors. They have increased affinity for serotonin /J-11I, receptors compared $ith D" receptors. They exhibit reduced ability or an inability to induce EPS. Second generalion agcnts include clozapine, risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole.

\e\\er

* ith first

Important: (Abilrj,/ is the first ofa new class of atypical antipsychotic agents called dopamine |. ^ripipr^zole sistem stabilizers or dopamine partial agonists.It combines the actions ofD2 and serotonin 5-HT2a
recePtor antagonism. :. Clozapine is specific for limbic recptors and not for striated (muscle) r.ceptors,which explains the low incidence ofEPS andTD.

.{ntipsychotic agents include: . First generation (lr^pical) agentsl

I

Phenothiazines:

. Chlorpromazine (Thorazine)

. Perphenazine
. Thioridazine . Prochlorperazine (Compazine) . T rifrtroperczrne (S t e I azin e)

. Mesoridazine . Fluphenazine

But'"rophenones:

. Haloperidol is a highly effective antipsychotic drug used to treat schizophrenia. ln addition it has been found to be effective in the heatment ofTourette's s).ndrome.

i.
.

Thioxanthenes:
a less potent

. Thiothixene is

antipsychotic. It is used for the treatment ofschizophrenia.

Second generation (a\)pical) agnts: this group includes clozapine, risperidone, olanzapine. quetiapine, ziprasidone, and aripiprazole. These drugs are effective in treating schizophrenia and exhibit reduced ability or an inability to induce EPS.

Adyerse effects of antipsychotic drugs:

. Dystonia and akathisia (an unpleasant sensation of motot' restlessness) . Long QT-interval syndrome and ultimately increase the risk of fatal arhythmias
. Neuroleptic malignant syndrome

. Parkinsonism
. Antimuscarinic effects . Orthostatic hypotension . Con\.ulsions

. Chlorpromaz ine

. T hioridazine

(Me I I ar i I)

. Risperidone (Risp erdo I)

Azelastrne (Astelin)

. Quetiapine (Seraquel)

. Clozapine (Clozaril) . Olanzapine (Zyprexa)

. Halopeidol (Haldol)
102
Coplrighr O 2011,2012 - Dmtal Decks

Which statement describs the extrapyramidal syndrome (EPS) caused by the phenothiazine'type lntipsychotics?

. Onhostatic hypotension

Sedation

. Headache

. Dry mouth
. Muscle spasms ofthe oral-facial region

103 Coplaight O 20ll-2012 - Denral Decks

*** Azelastine (Astelin)

Antipsychotics

is an antihistamine nasal spray.

are primarily indicated for treatment ofpsychosis associated with schizophrenia, paranoia, and manic symptoms of manic-depressive illness

Typical antipsychotic drugs (lirst generation) are more potent antagonists of D2 dopamine receptors than ofDl receptors. First generation drugs include the phenothia,zines (chlorpromazine, fluphenazine, perphenazine, prochlorperazine, trifluoperazine, mesoridazine, and thioridazine) , the thioxanthines (/riothixene) and the butyrophenones

(haloperidol). Note: Haloperidol is a potent dopamine antagonist. Newer (secontl generation) or atypic l antipsychotic agents affect different receptor siles compared with first generation antipsychotics. They bind dopamine, including D1, D2, Da, and D5 receptors, with selectively for limbic dopamine receptors. They have increased at'linity for serotonin (5-HT ) receptors compared with D2 receptors. They exhibit reduced ability or an inability to induce EPS. Second generation agents include clozapine, risperidone. olanzapine, quetiapine, ziprasidone, and aripiprazole.

Ertrapyramidal syndrome lEP.l) refers to a variety of signs and symptoms that are a result ofthe blockade ofdopamine receptors in specific brain regions. These symptoms include: Parkinsonlike movements (shufiIecl gait, pill-rolling eJlbct oJ fngers), muscle rigidiry. spasms ofneck and facial muscles, tremors, and loss of muscle movement.
Tardive Dvskinesia (TD) is a serious, irreversible neurological disorder that can appear at any age. Tardive Dyskinesia is a side effect of taking antipsychotic/neuroleptics drugs. Symptoms involve rurcontrollable movement ofvarious body parts, including the body trunk. legs, arms, fingers, mouth, lips, or tongue. About 20 percent ofpeople taking antipsvchotic/neuroleptic drugs for more then one year will be affected. Remember: Newer (second generation) or atypical antipsychotic agents affect different receptor sites compared with first generation antipsychotics. They bind dopamine, including Dl, D2, Da, and D5 receptors, with selectively for limbic dopamine receptors. They have increased alfinity for serotonin (5-HT) receptors compared with D2 receptors. They exhibit reduced ability or an inability to induce EPS. Second generation
agents include clozapine, risperidone, olanzapine, quetiapine, ziprasidone, and aripipra-

zole.

Important: Clozapine is specific for limbic receptors and not for stdated (muscle) receptors, which explains the low incidence of EPS and TD.

. Tinnitus (ringing in . Yertigo (dizziness)

. Nausea

the ears)

. Hallucinations
. Respiratory alkalosis

. Vomiring

104
Copyright O

20ll-2012

Dental Decks

. Percodan

. Vicodin . Motrin

ES

. Naprosyn

105

Copfight

20i |,2012 - Denral Drcks

An overdosage of saficyl^tes (aaie aspirin /o-riciry/ is life threatening and requires intensive supportivc trcatment in a hospital. Initial symptoms include respiratory alkalosis with hypcrpnea and tachypnea, nausea, vomiting, hlpokalemia, tinnitus, headache, dizziness, confusioq dehydration, hyperthermia, hypcractivity, and hcmatologic abnormalities, progressing to coma and respiratory collapse.

Chronic aspirin toxicity presents with the following signs and symptoms: salicylism, CNS effects,
bleeding and GI disnrrbances.

Aspirin inactivates the enzyme known as cyclooxygenase. Sincc cyclooxygenaso synthesizes thc prostaglandins, the inhibition ofthis enz''rne results in the inhibition ofprostaglandin synthesis. As a result, aspirin is analgesic, antipyretic (ever reducing), and anti-inflammatory. Aspirin is an irre versible platlet inhibitor and can reduce blood clotting to prolong bleeding. Note: Aspirin inhibits both COX-l and COX-2. Low doses of aspirin taken regularly can have a cardioprotective effect. These doses reduce thromboxane production in platelets to result in the inhibition ofplatelet aggregttion. In this way, aspirin has
the ability to inhibit the formation of life-threatening thrombi (6/0011clo/s/.

The lirer appearc to be the principal site for salicylate metabolism, although other tissues may also be in\ ol\ ed. Ihe three chicf metabolic products ofsalicylic acid are salicyluric acid, the cthcr or phcnolic glucuronide and the ester or acyl glucuronid. Excretion ofsalicylates occurs principally via the kidn), through a combination ofglomerular filtration and tubular cxcrction, in the form offree salicylic acid. salic] luric acid, as well as phenolic and acyl glucuronidcs.

Contraindications to the use ofaspirin: . Bleding disorders (aspirin will increase bleeding tine) ' Do not use in children with viral infections (i.e., i,fluenzu or chiclerpoxl with or without fever due ro a potcniial association with Reye's syndrome (this s), dlotne is a serious neutulogical defecl) . Pregnancy (especictlly during the thit'd lrinester) ' Pptic ulcers faipil'i nay cduse bleeding ofthe GI tracl) . .{sthma; rhinitis; nasal polyps . Concomitant use of anticoagulants

.\dYil contains 200 mg ofibuprofen and may be sold over-the-counter; whereas, Motrin contains .100 mg of ibuprofen or higher and can only be sold with a prescription.
\onsteroidal anti-inflarrunatory drugs (NSAID, have anti-inflammatory effects resulting frorn their ability to inactivate the enzyme prostaglandin endoperoxide synthase f.]cloon'genase).By doing this they inhibit the cyclooxygenase step ofthe arachidonic acid cascade and thus reduce local prostaglandin synthesis. NSAIDs also have analgesic, and antip)'retic actions. Remember: The traditional NSAIDs such as ibuprofen, naproxen and aspirin inhibit COX-2 along with COX-I. Thus they are effective in reducing pain and inflarnrnation, but are capable ofinducing gastrointestinal ulcers. The COX-2 selective inhibitors will reduce pain and inflammation without any significant risk ofcausing gastrointestinal ulcers.

For the traditional NSAIDS such as ibuprofen, naproxen, and aspirin, because they inhibit both COX-1 and COX-2 enzymes, they belong to the category of non-selective COX inhibitors. For celecoxib (Celebrcx), because it inhibits COX-2 enzyme only' it belongs to the category oICOX-2 selctive inhibitors.

Note: Rofecoxib (Woxx) and Valdecoxib (Bextra) are also COX-2 selective inhibitors that u,'ere removed from the market because they were found to have added cardiovascular risks in some Datients.

. Ibuprofen (Motrin, Advil)

Acetaminophen (Ty I e n o I)

. Aspirin . Naproxen sodium (l/eve)

106

Cop)"ightO20ll,20l2

- Denral Deckj

. Codeine

. Acetaminophen . Hydrocodone . Ibuprofen

107

Coplrighl O

201

1-2012 - Dental Deckt

Acetaminophen has no effect on platelets nor the coagulation pathways and does not affect bleeding times or prothrombin times even with high doses. Acetaminophen has two major pharmacological actions: an analgesic effect and an antipyretic (ever redticey' effect. Acetaminophen is not effective enough to reduce severe pain, but it is effective in reducing mild to moderate pain. Acetaminophen is a weak inhibitor of prostaglandin format ion.
Large doses ofacetarrinophen can cause liver toxicity. Alcohol can seriously increase the hepatotoxic potential of acetaminophen. There are approximately 100 deaths annually due to liver toxicity produced by ingesting large continuous doses of acetaminophen. Acetaninophen very rarely causes drug sensitivities and can be given to patients having an allersv to asnirin.

Affect blood clotting

Associated with Reye's s)ryldrome

Ibuprofen inhibits the production of prostaglandins in peripheral tissues at sites where pain and inflammation are present. Inhibition of prostaglandin production reduces the inflammatory respons at sites of surgery, injury or infection. Reduction of inflammation results in reduction ofperceived pain.

Acetaminophen is a weak inhibitor ofprostaglandin production in peripheral tissues. Thus, the inflammatory response is not affected to any great degree. Acetaminophen reduces pain through mechanisms other than inflammatory reduction. how acetaminophen uorks to reduce pain.

lt

is unclear exactly

Codeine and h1-drocodone are narcotic analgesics that effectively reduce pain but do not reduce inflammation. Narcotics work within the brain to block ascending pain impulses traveling from the periphery into the brain.

. Phenobarbital

. Ibuprofen
. Hydrocodone . Meperidine

. Codeine

108

Coplrigh O

201 I -20 12 - Dental Decks

NSAIDs reduce the production of associated with pain and inflammation.

. Leukotrienes . Cltokines
. Prostaglandins

. Interlerons

109

Coprighr C

201

l'2012 - Dental Dcks

Ibuprofen is

an

NSAID and is classified

as a

non-narcotic analgesic. Non-narcotic anal-

gesics have no

liability for

abuse or addiction. They are not a controlled substances.

Phenobarbital is a barbiturate used as a sedative and to treat epilepsy. Barbiturates all have the potential to cause abuse and addiction, and are controlled substances requiring a DEA number fiom the prescriber. Hydrocodone (Wcodin), meperidine (Demerol) and codeine are narcotic analgesics with the potential to cause abuse and addiction. They are all controlled substances requiring a DEA number from the prescriber

Important: NSAIDs can inhibit the antihypertensive effect ofACE inhibitors, betablockers. and diuretics.

Non-steroidal anti-inflammatory drugs 0y'S,4/Dl, inhibit the cyclooxygenase step ofthe arachidonic acid cascade and thus inhibit thc activity ofprostaglandin synthetase. Prostaglandins are a group of hormonc-like substances that mediate a range of physiological functions, such as metabolism and nen e transmlsslon.
and anti-inflammatory properties (similat to aspitin). They afihritis, and painful menstruation. Advcrsc reactions include GI upset @ossible ulcers), and prolongation of bleeding irme (reduction in plqtelel aggregatiotl). Contraindications to ihe use ofNSAlDs are impaired renal function, pregnancy, and GI disease 1r.r/cers)

\SAIDs have analgesic, antipyretic,

are used for pain control,

Eramples offSAlDs: . Proprionic acid derivatives:

. Flurbiprofen (,lnsaid) 'Oxaprczin (Daypro) . Ibuprofen (Motrin, Advil) . Ketoqofen (Orudis)

. \aproxen

'

Naproxen sodium (Anaprox, Aleve)

(Naprosvn)

'Fenoprofen (Nalfon)

. .{cetic acid derivatives:

. Indomethicin llndocll , Etodolac (Lodine) . Sullndac (Clinoril)

. Alkanoic acid derivatives: . Nabumetone (Relqfen)

. Dicloferac sodirm (Votaren) . Ketorolac (Toradol)

. Fenamic acid derivatives:

. Meclofenamatc

. Mefenamic acid lPorsle4 . Oxicams . Piroxicam (Feldene)

(M ec lomen )

. Meloxicam (Mobic)
. Cox-2 inhibitors . Celecoxib (Celebrcx)

. Ibuprofen

. Acetaminophen
. Aspirin . Naproxen
. Nabumetone

110

Coprighr O 20ll-2012 Dental Decks

. Amlodipine @y'onasc)

. Enalapril

(Yasotec)

. Ptroxrcarn (Feldene)
. Prednisone .
F

osamax (Alendronate sodium)

111 Copyrighr @ 2011,2012, Dental Decks

is analgesic for low intensity Acetaminophen inhibits central prostaglandin synthesis -it pain and antipyretic. Because it is less effective than salicylates (asplrlr/ in blocking peripheral prostaglandin synthesis, it has no anti-inflammatory activity and does not affect platelet function and therefore will not affect clotting time. Note: In large doses p Z 5 g within 8 hours), acelaminophen can cause hepatic necrosis. Concurrnt use with the following drugs may increase the risk of hepatotoxicity: barbitumtes, hydantoins, carbamazepine, rifampin, sulfi npyrazone, and ethanol. Acute overdosage ofacetaminophen can result in hepatotoxicity and is life threatening. Acetominophen is metabolized to a highly toxic intrmediate product, which normally is detoxihed by glutathione. When glutathione is depleted, the toxic intermediate attacks other cells, causing necrosis. Syrnptoms that appear in the ltrst 24 hours are nausea, vomiting, drowsiness, lethargy, malaise, and confusion. Note: N-acetylcysteine (NAC) is the specific antidote for acetaminophen poisoning.

Acetaminophen is preferred over aspirin when an analgesic or antipyretic drug is indicated and also the patient: . Is allergic to aspirin . Is asthmatic . Is at added risk for an ulcer . Is taking drugs such as probenecid or methotrexate . ls experiencing bleeding . Is taking anticoagulants

Remember: Aspirin and Nonsteroidal Anti-inflammatory Agens (Ibuprofen, Naproxen,

\qbumetone, and others) inactiYate the enzyme known as cyclooxygnase. Since cyclooxygenase s).nthesizes the prostaglandins, the inhibition ofthis enzyme results in the inhibition of prostaglandin synthesis. Cyclooxygenase has an acronym ofCOX' Thus the Nonsteroidal Anti-inflammatory Agerrts (NSAlDs) are also known as COX inhibitors. As a result, they ha\e analgsic, antipyretic, and anti-inflammatory actions. NSAIDS must be used cauriously in patients with peptic ulcer disease.

Piroxicam (Feldene) is a non-steroidal anti-inflammatory drug Qr'SlID) that inlibits prostaglandin synthesis. Il is used to manage inflammatory disorders and used for the symptomatic treatment ofacute and chronic rheumatoid arthritis and osteoarthritis.
Prednisone is a corticosteroid and has anti-inflammatory actions. It is used for the treatment ofa wide variety of inflammatory diseases including rheumatoid arthritis and os-

teoarthritis.
Rmember:

. Common side effects ofNSAIDs such

- Gastric irritation - Heart bum
- Nausea

as piroxicam (Feldene)

incl'tde:

. Short-term side effects of corticosteroids

- Insomnia - Indigestion

such as prednisone include:

Arthralgia . Long-term side effects of corticosteroids include:

-

- Edema (abdominal distension) - Psychological disturbances - Peptic ulcer - Osteoporosis

- Muscle weakness

. Salicyclates . Opiates . COX-2 selective inhibitors

. Non-selective COX inhibitors

. Steroidal anti-infl ammatories

112 Copright O
201 l-2012 - Denial Decks

. Epinephrine
. Norepinephrine

. Acetylcholine . Dopamine

113
Copyrighr O 2011,2012 - Denral Decks

Cyclooxygenase, or COX, is the enzyme which produces prostaglandins. Two forms of COX exist: COX-I, and COX-2. The COX-I enzyme produces prostaglandins in the GI

Tract. The prostaglandins formed act as a protective substance against the formation of gastrointestinal ulcers. The traditional NSAIDs such as ibuprofen, naproxen, aspirin. and others inhibit the COX-I enzyme thus diminishing the fomation of the protective prostaglandins. Gastrointestinal ulcers are therefore a potential adverse effect with these drugs. The COX-2 enzyme produces prostaglandins at the sites of surgery infection and inflammation. When this enzyme is inhibited, less prostaglandins are produced and there is less pain and inflammation. The traditional NSAIDs such as ibuprofen, naproxen and aspirin inhibit COX-2 along with COX-I. Thus they are effective in reducing pain and inflamrnation, but are capable of inducing gashointestinal ulcers. The COX-2 selective inhibitors will reduce pain and inflammation without any significant risk ofcausing gastrointestinal ulcers. For the traditional NSAIDs such as ibuprofen, naproxenJ and aspirin, because they inhibit both COX-l and COX-2 enzymes, they belong to the category of non-selective COX inhibitors. For celecoxib (Celebrex), because it inhibits COX-z enzyme only' it
belongs to the category of COX-2 selective inhibitors. The COX-2 selective inhibitors:

Are not salicylates because they are not aspirin drugs Are not opiates because they do not work like morphine Are not steroidal antiinflammatories because they are not corticosteroids such

as

hy-

droc ort isone

Chofinergic is a term for a nerve ending that releases acetylcholine (ACh) as the prrmary
neuotransmitter; also, a synapse in which acetylcholine is the primary neurotansmitter. Acetylcholine receptors are called cholinergic recepton. They are subdivided as follows:

. Muscarinic receptors fsites,): - At neuroeffector sites for all postganglionic cholinergic neurons (this is chqracteristic of a ll parasympathetic postgqnglionic nerves) At neuroellector sites ofpostganglionic sympathetic nrYes to the sweat glands and a few blood vessels (tl ese postganglionic nerves are also cholinergic)
-

. Nicotinic receptors (silesr:

-

At the skeletal neuomuscular junction (involving sonatic nerves) At ganglionic sites /*** The same type of nicotinic receptor is present in sympathetic

ganglia, parasympathetic gangliq, and the adrenal medulla)

Drugs that resemble ACh in chemical structure and bind to these receptors imitate the effects of parasympathetic postganglionic activity.

***

Important:
(l sympathetic) are cholinparasympathetic division. ergic. as are postganglionic neurons ofthe 2. Postganglionic neurons ofthe sympathetic division are usually adrenergic. 1. The action of acetylcholine at postganglionic parasympathetic sites is often referred to as a muscarinic response. \ote3 2. The term

L Preganglionic neurons ofboth divisior's (parasympathetic a

.. &tt:'

nicotinic response is used to describe the stimulating action ofACh

on the ganglia, as well as its actiol at the neuromuscular junction of skeletal

muscle.
3. Muscarinic receptors are usually linked to Go, phospholipase C (PLC), andCa".

. Slowing ofthe heart

. Dilation ofthe pupils . The stimulation ofthe smooth muscles of the bronchi, GI tract, gallbladder, bile duct,
bladder and ureters

. The stimulation ofsweat, salivary

tear and bronchial glands

114

Copltight O 20ll-2012 - Dental Deck

All of the following are antimuscarinlc agents .EXCrPf one. Which one is the IqXCEPTIOM

. Atropine

. Scopolamine . Gl) copynolate (Robinul)

. Vecamylamine (Inversine)
. Propantheline (Pro -Banthine)

115 Coptright
@

201l-2012 - Denhl Deks

***

This false; cholinergic action constricts the pupils.

Cholinergic actions:
. The stimulation ofsweat, salivary, tear and bronchial glands . The stimulation ofthe smooth muscles ofthe bronchi, GI tract, gallbladdel bile duct,
bladder and ureters (i.e., urinotion) . Slowing ofthe heart (bradycanlia)

. Constriction ofthe pupils

0n

rosrt

Important: Acetylcholine is the chemical mediator at all autonomic ganglia and parasympathetic postganglionic synapses. It is also the transmitter substance of the
neuromuscular junction in skeletal muscle (local anesthetics prcvent or rcduce the liberation of ACh at the NMJ) and sweat glands. Acetylcholine causes an alteration in cell membrane permeability to produce the above actions.

.{nticholinergic actions: .The secretions of all glands in the nose, mouth, pharynx and respiratory tract is inhibited (unpIeasant "dry mouth") . An inhibitory effect on motility throughout the GI tract fmal cause constipatio and uritla4 retention)
. The heart rate increass (tachycardia) . -\ rise in body temperature . Dilation of the puprls (mydriasis)

\ot:

Termination of transmission by ACh takes place primarily by metabolism by acetylcholinesterase located on postsynaptic or postjunctional membranes.

*** Ilecamylamine
The tvpical effects

is a nicotinic ganglion-blocking drug.

ofanticholinergic drugs include r.r.rydriasis, antispasmodic actions and gastric and salivary secretiorrs (dry moutlr).lmportant: These drugs are conreduction in traindicated in patients with glaucoma.
These drugs have no intrinsic activity oftheir own; they simply occupy the receptor site and pre\ ent acetylcholine from occupying the same receptor Accepted therapeutic indications include treating Parkinson's disease, motion sickless, postoperative bladder syndrome and traveler's diarrhea.

Inhibit salivation and excessive secretions prcoperatively; control ofupper airway sccrctions Travclcr's diarrhca and antisecretory

To produce mydriasis and cycloplegia To prevent or reduce motion sickness

. Mecamylamine
. Hexamethonium . Tetraethylammonium

. Trimethaphan

1t6
Cop)Tight O 201

I 2012,

Dental Decks

, Tubocvraflne (Curare) . }liYacuium (Mivacron) . Succinylcholine (Anectine)

. Vecuronium (Norcuron) . Doxacurium (Nuromax) . P anntr onium (P av u I o n)

.
.

Atracuium (Tracrium)
Cisatr

actiurn (N im b ex)
'117

. Rocuronium (Zemuron)

Copyrighr O 201| '2012 - Dental Decks

Hexamethonium, trimethaphan, and tetraethylammonium are no longer available in the U.S. for clinical use.

***

Nicotinic receptor antagonists (nicotitlic blocking agents) are divided into ganglionblocking drugs and neuromuscular blocking drugs. Remember: two major types of nicotinic receptors: 1. Those at the skeletal neuromuscular junction ofthe somatic system *** Neuromuscular blockers act here
2. Those at the autonomic ganglionic sites (both sympathetic atxd pqrasympathetic)

*** Ganglionic

blockers act here

Aldrough they are among the most potent agents available, ganglionic-blocking drugs are
seldom used because ofthe annoying and sometimes disabling parasympathetic ttlockade. The side effects (caused by parasympathetic blockade) tnc\rde a very pronounced xerostomia, constipation, blurred vision, and postural hypotension. These drugs have only

\'ery limited clinical uses.

\Iecam.'-lamine (nversile) is used clinically for:

. The treatment of

severe or malignant hypertension

. An emergency hypertensive crisis *** lt cause a rapid and reversible fall in blood pressure that enables it to ilrlnediately
reverse an emergency hypenensir e crisis.

. A "bloodless field" surserv

\euromuscular blocking drugs are important for producing complete skelctal muscle relaxation and
facilitate endotracheal intubation, as an adjunct to surgical anesthesia. These agcnts interact with nicolinic receptors at ihe skeletal neuromuscularjunction. Thcrc are t$o classes ofneuromuscular blockers:
These agents competitively compete with acetylcholine at the nicotinic recepnicotinic cholinergic receptors and prevent acetylcholine from stimulating moror nenes. resulting in muscle paralysis. The prototlTre nondepolarizing agent is tubocurare /Cr-

l. \ondepolarizing:

rrrr. Thesc agents bind to

|rrrer Other

agents include mivacurium, vecuronium, doxacurium, pancuronium. atracunum,

crsatracurium and rocuronium. Note: Neostigmine or pyridostigmine (which are cholineslerase i4hibitots) can reverse the blockade ofthese agents. :. Depol^rhing (non-(onpelilire): S:'lccinylcholine (Afiecttue) is thc only member ofthis group used rn the Unired Statcs. It acts like a nicotinic agonist and depolarizes (dese/tsilizes) theneuromuscular end pla1e. It binds to the ACh receptor and stimulates depolarization causing initial excitation follo\1ed bt- block of n eurotransmis sion and muscle paralysis. Important: Succinylcholine should be used with caution in patients with low Ievels of pseudocholinesterase, which breaks down succinylcholinc. Respiratory failure may result.

***

Succinylcholine may cause muscarinic responses such as bradycardia and incrcased glandular se-

cretions,

Very important: The major danger ofall ofthese ncuromuscular blocking drugs is too much paralysis (the patient cdnnol hrealhe).

1 Dantrolene is an skeletal muscle relaxing agent that acts within the skeletal muscle fiber rather than on the neuromuscularjunction fdoes not block the icolinic receptors).lt inhibits the depolarization-induced release of Car- from the sarcoplasmic reticulum The principal therapeutic applications ofdanffolene are for the re lief of spasticities associated with upper motor ncuron disorderc (i.e., slroke, cerebral palsv, and muhiple sclercsis) and for the prophylaxis and treatment of malignant hyperthermia. 2. Botulinum toxin A fBolo-rl acts on the motor nervc terminal to prcvent the release of ACh. It is used in ophthalmology to relax the extraocular muscles, and for muscle dystonias
as

well as to remove wrinkles.

. Physostigmine
. Edrophonium . Pyridostigmine . Phentolamine . Neostigmine

118

Coplright O 201 l-2012 - Den6l Decks

Alf of the foffowing are cholinergic d .:ltgs EXCEPT one. Which one is the -EXCEPIIOM

. Acetylcholine

. \4ethacholine . Bethanechol (Urecholine) . Dobutamine

. Carbachol (Isopto-Carbachol)

. Pilocarpine hydrochloride

119
Copyright O

20ll-20t2

- Denlal Decks

*** Phentolamine (and phenotybenzamine)

receptor blockeIS.

are prototypes ofnon-selective alpha-adrenergic

Cholinesterase inhibitors act by blocking the enzyme (qce4,lcholi esterase) that degrades acetylcholine in the brain. This results in more acetylcholine in the s).naptic cleft and enhances cholinergic transmission. These drugs act as indirect agonists at both muscarinic and nicotinic sites. Examples of cholinesterase inhibitors include: . Edrophonium: reversible; very short duration ofaction; used to reveffe cumre-type drugs . Neostigmine: reversible; extended duration ofaction; used to reverse curare-type drugs and to treat myasthenia gravis . Physostigmine: reversible; short duration ofaction; used for glaucoma, and for an antidote for atropine . Pyridostigmine: reversible; extended duration ofaction; used to treat myasthenia gravis . Tacrine: reversible; extended duration of action; used to Alzheimer's disease . Donepezil: reversible; extended duration ofaction; used to Alzheimer's disease . Malathion: irreversible; long duration ofaction; used as an insecticide . Sarin: ineversible; long duration ofaction; used as a nerve gas
Three cholinesterase inhibitors are commonly prescribed for Alzheimer's disease:

. Donepezil (Aricept), approved to treat all stages of Alzheimer's disease . Rivastigmine (Exelon), approved to treat mild to moderate Alzheimer's . Gafantamine (Razadyne), approved to treat mild to moderate Alzheimer's

\ote:

The stimulation of the skeletal muscle by excess acetylcholine eventually results

in muscle oaralvsis.

*** Dobutamine is an adrenergic agonist. Cholinergic drugs are compounds that mimic the actions of the endogenous neurotransmitter acctyl_ chofine /,4 Clrl. Direct-acting, or cholinomimetic, agents combine with cholinergic receptors (muscorimic or nicotinic or both), to cause a response in an effector. These drugs include ACh, various choline-ester congeners ofACh, and some alkaloids. With few exceptions fi.e., nicotine and olher ganglionic stintu1drlt, these agents exe.t prominent muscarinic or parasympathomimetic effects. These drugs are longerlasting than ACh because they are not subject to rapid metabolism like ACh. ACh is metabolized
by acetylcholinesterase, located near receptors forACh. In the plasma and other sites, ACh (and many olher esters) are rnetabolized by pseudocholinesterase. The other cholinergic agonists used as drugs are metabolized slowly or not at all by these enzymes.

Direct-acting agents:

. Choline esters: The most noticeable effects ofthese drugs are a fall in blood pressure attributable
to generalized vasodilation, flushing ofthe skin, a slowing ofthe heart rate, and an infieased tone and actilit-v of both the CI and urinary tracts. Topical application ofthese drugs to the eye causes miosis and a decrease in innaocular pressure. These dmgs include:

. Acet:-lcholine chloride: used in ophthalmology to produce miosis . Bethanechol: used for postoperative abdominal distcnsion and urinary rctention . Carbachol: used in ophthalmology to produce miosis . Cholinrgic alkaloidsi These drugs include muscarine, pilocarpine, nicotine and lobeline. Pilocarpine is the most useful alkaloid being employed as a miotic and to treat open angle glaucoma Pilocarpine is also used to stimulate salivary flow in patients suffedng ftom xerostomia due to radiation therapy in the treatment ofhead and neck cancer.

Indirect-acting agents:

. Cholinesterase inhibitors: These drugs include physostigmine, edrophonium, pyridostigmine, neostignine, malathion and sarin. They inhibit acetylcholinesterase at both mucarinic and nicotinic sites. They are indirect agonists at both muscarinic and nicotinic sites.
Note: Ifany ofthe cholinergic agents are administered before acetylcholine, the action ofacetycholine

will

be enhanced and prolonged.

. Produce a dry field for taking impressions

. Calm an anxious patient

. Treat dry mouth by inducing salivation

. Reduce nausea

120
Cop).righr O 2011,2012 - Dental Decks

All of ihe following statements concerning edrophonium EXCEPT one. l'/hich one ls the EXCEPZOM

Nrre

true

. It is a direcGacting cholinergic agonist (cholinomimetic) . It is

a rapid-acting, short-duration, injectable cholinesterase

inhibitor

. It is the drug of choice for diagnosing myasthenia gravis because of its rapid onset of
action and reversibility

. It is also useful in differentiating

a myasthenic crisis from a cholinergic crisis

121 Coplright O 201l-2012 - Denral Decks

Cholinergic drugs used in dentistry are: Pilocarpine (Sa/agezl, and Cevimeline (Evoxac). is indicated for treatment ofxerostomia caused by salivary gland hypofunction resulting from radiotherapy for cancer of the head and neck. It's pharmacologic category is cholinergic agonist. Prevalent side effects are excess sweating and nausea./heartbum/diarrhea due to the cholinergic nature ofthe drug.

. Pifocarpine (Salagen)

. Cevimefine (Evoxac) - is indicated for the treatment of symptoms of xerostomia in patients with Sj<igren's syndrome. It's pharmacologic category is cholinergic agonist. Prevalent side effects are increased sweating and nausea/heartburn/diarrhea due to the cholinergic nature ofthe drug.

This is falsei edrophonium is an indirect-acting cholinergic agonist (cholittomimetic) as are pyridostigmine, physostigmine, and neostigmine (thq, are qll cholinesterase inhibitors). \ote: These drugs are indirect agonists at both muscarinic and nicotinic sites.

***

Pyridostigmine is prescribed in the treatment ofmyasthenia gravis, however edrophonium is used to diagnose myasthenia gravis and not in the treatment ofit due to its Yery short du-

ration of action,
Symptoms ofa cholinergic crisis include bradycardia (decreased heart rate),lacrimation, extreme salivation, vasodilation and muscle weakness. Because a cholinergic crisis can result in muscle weakness like that ofa myasthenic crisis, distinguishing the two conditions may be dif-

ficult. Administration ofa short-acting cholinomimetic such as edrophonium will improve ml asrhenic crisis but worsn a cholinergic crisis.

Remember: Typical cholinergic effects caused by stimulation of acetylcholine receptors kholi ergic receptorg include salivation, miosis, excessive sweating, flushing, increased GI motility and bradycardia.

Poisoning with an organophosphrte cholitrssterase inhibitor can be treated with:

. Edrophonium

. Carbachol
. Pralidoxime . Nicotine

122
Cop)rigbt O 201l-2012 - Dntal Decks

. Miosis

. Flushing . Bronchoconstriction
. Increased GI motility . Increased urination . Tachycardia

. Salivation
. Increased urination

Sweating
123
Coplrighr O

20ll-2012

Dental Dcts

Pralidoxime (Protopam) is a cholinesterase reactivator which is used as an antidote to reverse muscle paralysis resulting from organophoshate anticholinesterase pesticide poisoning. It is also used to reverse the effects of an overdosage of anticholinesterase agents used in the treatment ofmyasthenia gratts (i.e., pyridostiSmine and ambenomium).
Symptoms of organophosphate poisoning include: excessive salivation, bronchocostriction, diarrhea and skeletal muscle iasciculations (twitching).

Organophosphates are esters ofphosphoric acid and an organic alcohol that inhibit the
enzyme cholinesterase.

Examples include:

. . . . . . .

Isoflurophat: used in the treatment ofglaucoma Malathion: a widely used insecticide Parathion: an insecticide Echothiophate: used in the treatment ofglaucoma Tabun: one ofthe most potent and toxic nerve gases
Soman: nerve gas

Sarin: nerve

gas

*** Bradlcardia

is a muscarinic effect ofcholinergic agonists.

Direct-acting cholidergic drugs include: methacholine, carbachol, bethanecol and pjlocarpine.

Indirecl-acting cholinrgic drugs (cholikesterase inhibltor.r/ includc: physostigmine, edrophonium, neostigmine. pyridostigmine, malathion, echothiophate, sarin and soman.
Effects of anticholinesterases: Muscarinic:

. Bronchoconstiction . Salivation .lncreased GI motility

Miosis

Nicotinic: . Muscle twitching

. weakness . Tachycardia . Increase in BP

'Sweating ' Urination .

Bradycardia

Antimuscarinic drugs block the effect ofacetylcholine and all drugs that stimulate muscarinic rcceptors. Atropine and scopolamine arc prototlpes. Other antimuscarinic drugs include: glycopltolate,
propantheline, benztropinc, cyclopcntolate, tropicamide, trihexyphenidyl, homatropine, oxybutynin, and

rpralroplum.

Antimuscarinic drugs produce the following effects: . Salivary glandsr red\tced secretion (atropine) . GI tract: reduced peristalsis, reduced secrelion (ptupa theli . Su eat glands: reduced sectetion (atropilte) . E1-es: mydriasis /lotuatropine, clclopentolale, tropicamide) . Bronchi: bronchodilation, reduced secretion (ipratropium) . Bladder: urinary retcnt\or (oq'but)nin) . C\S: antimotion sickness 6copolamine)
antitremor activity

e,

g6\:opvrrolate)

l.

Coohaindications for using antimuscarinic drugs include: narrow-angle glaucoma, prc-

-to

treat parkinsonism fbenztrcp[ e, trihe$'phenidyl)

Noreq; static h)?crplasia, and tachycardia. 2. Pilocarpine and cevime\ne (both cholinergic dsorTr.J/t are used to stimulate salivary flow 3. SAL-TROPINElatropine sulfate, USP tablelt is indicatcd to reduce salivation and is endorsed with the ADA Seal ofAcceptance

. Atropine sulfate
. Carbachol

. Glycopyrrolate (Robinul)
. Belladonna derivatives . Propantheline bromide (Pro-banthine)

124
Coplright
@

201l-2012 - Dnhl Deks

. Triamcinolone

. Cortisol
. Dexamethasone

. Prednisone . Prednisolone

125

CopFgh

O 201l-20l2 - Dental Decls

***

Carbachol is a direct-acting cholinergic drug.

The other drugs are all classified as anticholinergics. They block postganglionic cholinergic fibers.

Contraindications to their use include:

. . . .

Glaucoma Cardiovascular problems Obstruction of the GI or GU tract

Asthma

These drugs also reduce spasms of smooth muscle in the bladder, bronchi, and intestine; relax the iris sphincter; dcrase gastric, bronchial, and salivary secretions; decrease perspiration; and accelerate impulse conduction through the rryocardium by blocking vagal

imoulses.

Tte corticosteroids are steroid hormones produced by the rdrenal cortex, They consist oftwo major
groups:

l. Glucocorticoids: have irnportant effects on metabolism, catabolism, immunc responses and inflammation. Tle majo ty ofthe anti-inflammatory and immunosuppressive actions ofthe glucocorticoids are probably the result of their action on arachidodic acid metabolism. They induce the synthesis of a protein that inhibits pbospholipase A2, thus decreasing the production of both
prostrglandins and leukotrienes.
The major natural glucocorticoid is cortisol. The synthetic glucocorticoids include hydrocortisone (Cortef), .ortisone, prednisone (Delatasone), predrisolone (Delta-Cortef), dexamethasone (Decadtuh), triamcinolone (Aristocort), firethylyprednisolone fMed,"d/), and betamethasone lces/or?e/. Glucocorticoids are most often used as anti-jnflammatory and immunosupprcssive agmts.

Adverse effects ofthe short-term administration ofsystemic glucocorticoids include secondary infections, hlperglycemia, and a range ofmood and behavioral changes. Loog-term therapy may cause osteoporosis, cataracts, hypertension, myopathy, and adrenal ins!fiiciency.
2. Mineralocorticoids: regulate sodium and potassium reabsorption in the collecting hrbules ofthe kidney. The major natural mineralocorticoid in humans is aldosterone. Other mineralocorticoids include deoxycorticosterone and fludrocortisone. Mineralcorticoids are used in replacemcnt thcrapy in hypoadrenocorticism or Addison's disease.

\ote:

Corticosteroids do not cure any disease. They represent replacement only in Addison's disease.

use include: latent TB or fungal infection, AIDS, herpes infections drugs themselvcs may cause and patients with peptic ulcer disease (specrfcally, gastric ulcers) -these pephc ulcers.

Contraindicrtions to conicosteroid

Toric effects ofthe corticostercids include growth inhibition, hlperglycemia, osteoporosis, psychosis and
salt retention.

All of the following are pharmacologic effects of glucocorticoids EXCEPT Orc. WbiCh ONE iS thE EXCEPTIOM

Stimulate protein breakdown, which results in increased plasma amino acid levels
use

. Stimulate gluconeogenesis in the liver and inhibit peripheral glucose . Impaired wound healing
. Reduce the immune response

Decreased lipolysis edema, capillary dilation, migration and activation of white blood cells, and phagocytosis by macrophages and increase the numbers ofcirculating red blood

.Inhibit local

. Increase hemoglobin concentration

cells and platelets

copy'igl e zor11!112

o*orn."r,

. Dexamethasone
..Aldosterone

. Cortisol

. Prednisone . Triamcinolone

127 Coplright O 201l-2012 Dsnlal Decks

*** This is false; glucocorticoids

affect the mobilization of fats from areas of deposition. Increased Iipolyisis occurs in areas ofadipose accumulation, and serum fatty acid concentration increases. Other effects of glucocorticoids include an anti-inflammatory action, immunosuppression, and an anti-allergenic action. Note: These effects occur in target cells following the interaction ofthe steroid with a specific glucocorticoid receptor

\ote: Beclomethasore, budesonide and flunisolide are special glucocorticoids /used as inhalers) that hale been developed for use in chronic rsthmr and bronchial disease. These agents readily penetrate the airFay mucosa but have very short half-lives aftr they enter the bloo4 so that systemic effects and
toricity
are greatly reduced.

Remember: The pharmacologic effccts of mineralocorticoids include an increase in sodium rctention and an increase in potassium depletion which can lead to edema and hypertension if excessive and
may lead to dehydration and hypotension

ifinsulficielt.

***

Cortisol, prednisone, dexamethasone, and triamcinolone are all glucocorticoids.

Aldosterone is secreted by cells located in the zona glomerulosa ofthe adrenal cortex. The secretion ofaldosterone is regulated by ACTH and by the renin-angiotensin system and is very important in the regulation of blood volume and pressure. Aldosterone promotes rerbsorption ofsodium into the blood from the glomerular filtrate. Potassium is lost in the urine because of the electronegativity that is created by the reabsorption of sodium in the kidney tubules. Note: Increased blood aldosterone levels will result in high sodium and low potassium levels in the plasma.

Remember: Decreased sodium concentration causes the juxtaglomerular cells of the kidneys to secrete renin, which converts angiotensinogen to angiotensin I. Angiotensin I is converted to angiotensin II, which, in tum, stimulates the adrenal cortex to release aldosterone.

, -,- ,. 1. Addison's disease is caused by the hyposecretion of aldosterone and corti-rNote{,] sol. 2. ADH (Vasopressin) decreases the production of urine by increasing the re*if' absorption of water by the renal tubules (it increases the permeobiliry of the collecting ducts and distal tubules). Without ADH, there would be extreme
Ioss
3.

ofwater into the urine.

causes arterioles to

At high concentrations, ADH

constrict (increases blood

Dressure).

. Hydrocortisone . Prednisone

. Cortisone
. Fluticasone (Flonase) . Methylpredrisolone (Medro I)

124
Coplaight O 201l-2012 - Dstal Decls

. Hydrocortisone . \{ethylprednisolone
. Prednisone

. Compazine . Triamcinolone
. Dexamethasone

129 CoplriSh O
201 1,201 2 - Dental Dects

Corticosteroids in the inhaled form, decrease the inflammation in the airway in asthma. Reduction of inflammation enhances the bronchodilating effects ofthe beta2-adrenergic
agonists.
The following are some ofthe other popular inhaled corticosteroids used in the treatment

of asthma: . Triamcinolone (Azmacort) . Beclomethasone (B eco n.tse ) . Budesonide (Pulmicort) . Flunisolide (AeroBid) Note: Inhaled steroids very often cause a fungal infection ofthe mouth and throat.
Combination products used in the treatment ofCOPD and asthma include:

. albuterol/ipratropir'l'm (Combivent) . fluticasone/salmeterol (Advair Diskus)

. budesonide/formoterol (Symbicort)

ainr ay obstruction. There are two subclasses: (l) Leukotriene receptor antagonists which include montelukast (Singulair) and zafirlukast (Accolate) (2) 5Jipoxygenase inhibitor tleukotriene s!nthesis inhibitor) which includes zileuton (Z,tflo).

Important: Leukotriene modifiers act on inflammatory mediators ofasthma, the LTs lalso htoutr as slo$.reqcting substance of anaphylnris [SRS-A]), which contributes to

***

Prochlorperazin e (Compazine) is an anti-psychotic medication in a group ofdrugs called

phenothiazines. T\\'o r-ypes of corticostroids:

L Glucocorticoids affect carbohydrate, lipid, and protein metabolism. They are used as to treat numerous disorders, primarily through their anti-inflammatory and immunosuppresslve acnons. 2. Mineralocorticoids regulate sodium and potassium metabolism.

l. These dmgs are used to treai a variety ofconditions which include asthma, arthritis, allergies, aphthous stomatitis, lupus erythematosus, and TMJ pain. 2. Contraindications to their use include latent infections (fingal, viral, or bacte' ndr, AIDS, herpes infections, gastric ulcers, and congestive heart failure. 3. Adverse reactions include Cushing's syndrome (obesit)' qnd weakening oJ uuscles), hyperglycemia, osteoporosis, peptic ulcers, and an increased risk of infection. 4. Corticosteroids do not cure any disease. They represent replacement only in Addison's disease.

Inhaled corticostroids used for asthma do not achieve significant blood levels to cause the advene effects listed above for systemic agents. Populal aerosol corticosteroids are triamcinolone (Azmacort), beclomethason freconase),fluticasone (Flovmt) andbudesonide (Palnicott). Localized infections with Candida albicans occur frequently in the mouth and pharyrx with repetitive use of inhalant corticosteroids.
Nasal spray corticosteroids used for seasonal allergies also do not achieve significant blood levels, and are use for their localized effects. Popular nasal spray corticosteroid products are triamcinolone fNasocorf , fl uticasone (Flonase) and budesonide (Rhinocort).

All of the following drugs ar direct vasodilrtors .EXCEPZ one. Which one ls the TXCEPZOM

. Hydralazine (Apre s o I ine)

. Diazoxide (Prcglycen)

. Captopril .

(Capoten)

Sodium nitroprus side Qtlipride)

. Nitroglycerin (Ni tros tat)

130
Cop).right O 2011,2012 - Denral Dcks

AII ofthe following drugs are used ao prevent or to provide relief of angina pectork EXCEPT one. Which one is the EXCEPTIOM

. Nitroglycerin
r I<nfl,,rnnhqtp

Qtt i t ros

tat)

. Nifedipine (Procardia)
. Dlltiazem (Cardizem) . Propranolol (Indera l)

. lsosorbtde (Isordil)

131

Coplrighr O 201 l-2012 - Dmral Decks

***

Captopril is an angiotensin-converting enzyme inhibitor.

Direct vasodilators exert their antih)?ertensive effect by a direct vasodilator action on the smooth muscle of arterioles, resulting in a decrease in peripheral resistance and blood pressure. Compensatory responses may be marked and include salt retention and tachycardia. Adverse side effects include GI upset, headache, dizziness and tachycardia.

Not: nitroprusside, diazoxide, hydralazine and nitroglycerin are parentral vasodilators which are used in hypertensive emergencies.

Calcium channel blockers are also effective vasodilators firclirect) ?J]'dhavebeen applied to the management ofhypertension. Vertpamil (Calan SR), Nifedipine (Procardia), and Diltiazem (Cardizen) have been given orally for the treatment of mild to moderate hypertenslon. Remember: Hydralazine and minoxidil are peripheral vasodilators.

***

Isoflurophate is an organophosphate cholinesterase inhibitor used in the treatment

ofglaucoma

Angina pectoris is the pain in the heart and chest which occurs during the occlusion ofcoronary arteries. Triggers that can cause occlusion are physical exertion, increased blood pressure, and vasoconstriction. Antianginal drugs work by reducing cardiac rate and force, reducing peripheral vascular resistance, or dilating coronary blood vessels. Nitroglycerin is a coronary artery vasodilator. It relaxes blood vessels to provide increased blood flow and oxygenation to the heart muscle. It is sublingually effective within
2-4 minutes. The nitroglycerin skin patch releases the drug over a 12 hour period to pro\ ide sustained blood levels for prevention ofangina. The two most common adverse effects caused by nitroglycerin are orthostatic hypotension and headache.

\ifedipine lProca rdia)

and diltia,zem (Carulizem) are calcium channel blockers used to

prevent angina attacks. These drugs are used to dilate coronary blood vessels for improred blood flow to heart muscle. Note: Calcium channel blockers as a class have been associated with causing gingival hyperplasia. Propranolol (lnderal) ts representative ofthe beta-blockers used to prevent angina attacks. Atenolol (Tenormin) is another popular beta-blocker used for this purpose. Betablockers are used to decrease the work load ofthe heart such that less oxygen is required.

Amyl nitrile is used ln ths emergency iratment of cyonide poisoning because it:

. Oxidizes hemoglobin
. Irreversibly binds cyanide

. Competes with cyanide for binding ofcy4ochromes

. Inhibits tubular reabsolption ofcyanide

132
Coplyight C
201

l-2012 - Deutal Decks

. Is dependent upon

a normal cardiac

rhythm

. Directly

increases the force ofmyocardial contractions

. ls antagonized by beta-blockers
. All ofthe above

133 Coplright
@

20ll-2012 - Dental Decks

nitrite oxidizes hemoglobin to methemoglobin which binds cyanide tightly, keeping it in the peripheral circulation and preventing its access to tissues.

*** Amyl

Amyl nitrite is a vasodilator and a highly volatile substance administered by inhalation only. It is the most rapidly acting ofthe antianginal drugs, producing effects within l0 seconds. Its duration of action is only 3 to 5 minutes. Because of its extreme potency, there are uncomiortable side effects that invariably occur with rts :use (ainting and a pounding headache). lmportant: This drug is rarely prescribed and is not the first drug ofchoice in treating angina. It is abused to produce euphoria and as a sexual stimulant.
Other anti-anginal drugs include:
This drug is the single most effective agent available for the management ofacute angina episodes. Note: It dilates mostly veins. 2. Non-nitrate vasodilator: Dipyridamole (Persantine) 3. Beta adrenergic blocking drugs: reduce cardiac rate and force . P ropr anolol (l ndera I)
1.

***

Nitrate: Nitroglycerin

. Nadolol (Corgard)

. Atenolol (Tenormin)
-1.

Calcium channel blocking drugs: dialte peripheral and coronary blood vessels . ltrapamil (koptin, Calan) . Diltiazem (Cardizem)
. N rfediorne
(P ro card ia )

This positive inotropic effect is independent ofa normal sinus rhythm and adrcnergic stimulation. Thc cardiac gf]cosides are often called "digitalis" because several come from the digitalis (lbxglove) plant. Digoxin /larroxir) is the most versatile and widely used. \otei The) are used to trcat most supraventricular arrhythmias, cardiogenic shock and chronic heart lailure.
These drugs help the heart beat more

***

strongly (posilire inotopic effect), more slo\\ly (bradycardia)

more elficientl].

^nd

Cardiac gl]cosides inhibit the Na*-K*-AlPase membrane pump by inhibiting the adenosine triphosphate enz)-mes (transport ATPase or Na-K-ATPase). Na*-K*-ATPasc splits adenosinc triphosphatc in the nel\e and muscle cell and thus provides the energy necessary for transporting sodium across the cell membranc. Key point: This inhibition of thc NalK*-AIPase enzyme leads to an increased calcium ion influx u'hich augmnts the positive inotropic effect ofcardiac glycosides. Adverse side effects include nausea and vomiting, appetite loss, dianhea, ventricular anhyhmias, heart block, and visual and mental disturbances. Contraindications to thci.use include ventricular fibrillation andventricular tachycardia.

Drug interactions: Many drugs aff'ect digoxin levels. However, digoxin docs not affect the levels ofother drugs. ln addition, when beta-blockcn are added to digoxin in patients with AV conduction abnormalities, complete heart block can result. Erythromycin. clarithromycin and tetracycline may increase digitalis absorption and toxicity. Thyroid replacement therapy incrcases dose requirements ofdigoxin. D gs that lower plasma potassium levels ae.&, lhiazide and loop diurelics/ increasc digitalis toxicity Drug treatment of mild to moderate heart failure proceeds in the following order:(l) Diuretics in patients \1ith fluid retention (2) ACEIS orARBS in all paticnts unless contraindicated (3) Beta-blockers in all stable inininalJluitl relention) p^tients unless contraindicatcd and (4) Digoxin. Note: Ifthese medications are not suflicient to control heart failure, the following additional drugs may be given: (1) Spironolactone (a aldosterone antctgorlist) (2) Nitrates and hydralazine and (3) Calcium channel blockers (i.e., amlodipine and felotlipine only) Remember: Most drugs useful in treating cardiac arrhythmias act primarily by increasing the re-

fractory period ofcardiac muscle.

. Captopril (Capoten)
. Hydralazine
(Apres
o

line)

. Enalapril (Vasotec)

. Lisinopil (Zestril)
. Fosinopril (Monopri l)

1U
Cop).right O 201 1,201 2 , Dntal Decks

. Propranolol (Inderal) . Acetbutolol fsectra,

. Metoprolol (Lopressor)
. Yeraparnil (Calan)

135

Cop)'ight O 20ll-2012 - DentalDecks

Hydralazine is a direct peripheral vasodilator. ACE inhibitors interfere with the convrsion ofangiotensin I (d veak rasoconstictol) to angiotensin ll (a highly e.f;[ective constrictor). Thcy do this by being inhibitors of angiotensin-convcrting enzyme
(,1CEl. These drugs are used to treat hypertension and congestive heart failure. Adverse cffects includc cough, hypotension, neuhopcnia, anorexia alrd pol]uria. Note: They can alter the sense oftaste and in a few rare cases, cause angioneurotic edema. Angiotensin II is a potent vasoconstrictor and is a stimulus for aldosterone release from the adrenal glands. Reduction in aldosterone secretion results in less waterabsorption and sodium/potassium exchange in the distal renal tubule, causing a slight increase in serum potassium. ACE inhibitors inhibit the breakdown ofbradykinin, a potent and naturally occurring vasodilator, by blocking thc cnzymc kininase IL This though, is thought to be the causc ofthe cough commonly experienced by patients who take this class ofdrugs.

***

OtherACE inhibitors f,4Ct1t include: . Benaz,eptll (Lotensir./ . Moexipril fLr?i|ascl 'Quinapril (Accupril) 'Captopril (Capoten) . R^rnipfll (Altdce) . Trandolaprll (Mat ik) ' Lisinopril (Zestil) ' Elan |{il (Uasolec) Angiotensin

lI

reccptor blockerc f,4RBs/ include:

. Losarlan (Coaaar) . \'alsafian (Diotan) . C andesanan (Atacand)

. Eprosaftan (Tevete

. Olmesaftan (Benicar)
. Tebllisafian (Mica rd i s)

.lrbesarlan (Avapro)

***

ARBs block the effects ofangiotensin II by blocking the binding ofangiotensin II to its rcccptors.

Thc: do not effect bradykinin. Adverse effects jnclude dizziness, diarrhea and myalgia.
Thc antih) pcnensive effects ofARBs have been provcn comparable with those ofthe ACEIs ACEIs and {RBs are ofparticular values for the reatment ofhypettensive patients who have concomitant illnesses iuch as diabetcs, rcnal insufficicncy, left ventricular dysfunction, and CHF

\ote: ACE inhibitors and Angiotensin II receptor blockers indirectly inhibit fluid volume increases \\hen interfering with angiotcnsin II because angiotcnsin II stimulates thc rlease ofaldosterone, which
promotes sodium and water retention.

Thc \ aughan-williams classification system traditionally has been used to classity antianhythmic drugs. This scheme places the available agents into onc of four classes, usually denoted by Roman numcrals I lV This systcm is loosely based on the channel or receptor involvcd. Class

l:

Sodium channel blockers

. Class I drugs are further classified on the basis oftheir effects on action potential duration:
. lA agcnts include; Qu:Lnidinc (Quinidex), procatnamide (Procan SR/ and disopyramidc py'orpaceJ. These agents prolong thc action potential. . fB agents include: LidocainelX.ylocai e). mexiletine (Mexilil) and tocainide (Tonocard. These agents shortn the action potential. . fC agents include: Flecainide (Tambocor) and propafenone (Rythnol). These agents have no effect on action potential dulalion.

Cfass II: Beta-adrenergic blockers Propranolol (Inderal) is the prototype antianh)'thmic beta-blocker Other drugs in this class include: esmolol (Breibloc) acetbutolol (Secn'al) ar'd metoprolol (Lopressor). These agents increase refractory period, decrease conduction velocity and reduce automaticity. Cfass IfI: Potassium channel blockers - Amiod^rone (Cordarore) is the prototype drug in this class. Sotalol (Betapace), tbutilide (Corvert) and dofetilide (Tiko$n) arc also in this class. These drugs increase refractory period and reduce automaticity. Class Il': Calcium channel blockers Yerapamil (Calan)is the prototype. Diltiazem is also included in this group. These drugs increase refractory period, decrease conduction velocity and reduce automaticity.

Note: Miscellaneous antiarrhythmic drugs include: adenosine (Adenocard) which increases refiactory period and reduces automaticity and digoxin (Lanoxin) which increases the force ofcontraction ofthe heart muscle and decrease conduction velocity.

. The first statement is true; the second statement is false

. The first statement

is false; the second statement is true

Both statements are true

. Both statements are false

136 Cop}fighr O

20ll-2012 DenialDecks

. Anglna

'

Hlpertension

. Suprayentricular tachyarrhy'thmias
. All ofthe above

137 Coplrighr O20ll-2012, Dental Dcks

Procainamidc is a Class lA antianhythmic agcnt that is uscd in thc trcatment ofseveral cardiac arrhythmias including atrial fibrillation, atrial flutter, parcxysmal atrial tachycardia. and ventricular tachycardia. It is not used as an antihypertensive. It is a derivative ofthe ester local anesthetic procaine. Procainamide has properties similar to those ofother Class lA agcnts, quinidine and disopyramide. These drugs decrease myocardial conduction velocity, excitability, and contractility by inhibiting the influx of sodium through "fast" channels oI the myocardial cell membrane, thereby increasing the rccovery period al1er repolarization. Note; Quinidine is prirnarily used to treat supmventricular tachyanhythmias.

Remember; Generally speaking, the use ofbeta-blockers (Class II agents) as antianhythmics is reserved fbr patients who require only control ofventricular ratc during atrial tachyarrhythnias or who have mildly symptomatic vent cular arrhythmias. Side effects includc bradycardia and hypotension.

Important: Amiodarone (Cordatone) is generally considered a Class Ill agcnt even though it also blocks sodium channels, a Class I action. It is uniqu in that it is the most potent and "broad-spectrurn" antianhythmic compound cunently available. It blocks sodium, calcium, and potassium
channels as rvell as beta rcceptors. Il has impressive ellicacy in suppressing both supraventricular and \ enlricular arhythmias. Note: Adverse effects include pulmonary fibrosis, thyroid abnormaliti!-s. skin discoloration, and peripheral neuropathy.

\ot.s

L Cornmon adverse effccts ofsome antiafihythmics: . Procainamide: nental changes, torsade de pointes (TDP - i.s an uncontnutn varia t ofvetlti'icul4r |acht-cqrdia) . Quinidine; hypotension, cinchonism @ eadache, ringing in lhe ears, deafness), awl
torsade de pointes

. Lidocaioei convulsions . Propranolol; bronchoonstriction, heart block

. Calcium channel blockers: flushing, headache, hypotension, gingival hyperplasia and reduced cont.actilitv ofthe heart

\-erapamif is the prototypical Class lY (celciu channel blockers) antiarrhythmic agent. It jnhibits the intraccllular entry ofcalciurn through the slow channels ofthe calcium dependent tissues of the myocardium, rvhich are concentrated in the SA and AV nodcs. It is the drug ofchoice for the suppression ofparoxysmal supraventricular tachycardias stemming from the AV node (wlrlclr is characteri:ed by a rcpid cer.liac rate, usually 160-190 per minule). Of the calcium channel antagonists available, only vcrapamil and diltiazem possess significant antianhythmic activity.

Note: Calcium channel blockers (e.g., verapanril, dillazem and nifedipile) are useful

as

antianginal agents and antihypertensive agents as rvcll. They block calcium cntry through the membranous calcium ion channels ofcardiac and vascular smooth musclc. This has thrcc cffccts:
1. Peripheral arteriolcs dilate

(vasodilato,", and total periphcral rcsistance deoreascs, reducing

after-load and reducing myocardial oxygen requirements. 2. lncreases oxygen delivery to the myocardium. 3. Reduces blood pressurc ifhypertension is present.

lmportant; Nilrites (amyl nilrite) and nitratcs (nittoglyceri\)

that are uscd to relieve acute anginal attacks.

are fast-acting antianginal agents

\ote:

For angina, nitroglycerin and nifedipinc arc usually used before verapamil.

. Enoxapadn (Lovenox)
. Dalteparin (Fragmin)

. Tinzaparin (Innohep) . Clopidogel

(PIavLx)

138 copynsht O 20ll-2012 - Denral Decks

Abciximab (Reopro)
Anagrehde (Agrylin)

. Epttfibatide (I nt e gri lin) . Tirofiban (Aggrastat)

139 Coplrighr O 201I-2012 - Dntal Decks

*** Clopidogrel fPlarrt inhibils blood clolting

a - - _ :tyotedr

by inhibiting platelet aggregttion in an irreversible manne.

L Thcsc typc ofanticoagulants agcnts f/olr mols.ular \|eight hepdin, arc uscd to treat acute symp_ tomadc dcep vcin lhrombosis. Tlrcy arc uscdlo preventdccpvcin thronlbosis following knce orhip su.-

-.... :,: l;i;*:.-

scry' 2. Thcy arc administcrcd subcutancously sincc they arc unablc lo bc absorbcd frorn the Gl tract. 3. Standard heparin consists ofcomponcnts wilh molccolar wcights ranging from 4.000 to 30.000 daltons with a mean of 16,000 daltons. Low molecular-lieight heparins rangc in molccular wcights from
4-

2,000 to 8,000 daltons. Heparin acts at multiplc sites in ihc coagulatior systcm and binds with antithrombin III at two spccitic sites, rcsulting in irs anticoagulanl cffcct- At thc first sitc factor Xa is tlcutlalizcd and at ihc sccord silc factor lIa A,rr?rrbr, is ncutralizcd. 5. Low molecular tleight heparins havc a small eflect on pa(ial thromboplastin timc but strongly in-

hihit factor Xa hol lla).

6. Thc antidote fbr heparin is

protamine; thc antidotc lbr warfarin is vitamin K.

Class Heparrn group Heparin

Subclass

Gcneric/tr|d Name
heparin sodium

Low molecular weight heparin

noxaparirlllovnox dalteparin/Fragmin tinzaparir/Innohep

Hepadnoids

danaparoid/Orgaran

fondaparinutAnXtra
Direct thrombin inhibitors bi\ alirudin/Aneiornax

a4atrobal'Argatroban
lepirudinr?.efludan
Oral anticoagulanls

warfanr/Coumadin
anisindione,tt4iradon

Glrcoprotein IIb,4Ila inhibitors

are reversible antiplatelet agents uscd !o prcvcnt acut cardiac ischemic complicfiions and used in paticnts with acute coronarv svndrome. Thev are adntinistered imtravcnously. rhe binding site for fibrinogen, von Willebrand r'3.tor. and othcr ligands. Inhibition of binding at this final common receptor reversibly blocks phtelt aggregation and prevenls thrombosis- Platclet aggregation inhibition is revcrsible following ccssation ofthc lV 3cmr:inration ollhc drug minutes after an intruvenous infusion. Note: The glycoprotein IIb/lIIa inhibitors h3! i a raPid onset ofaction, Their maximal antiplatelet effect occur within minutes after an intravenous in1-li[]r Important: Thc most serious adverse effects of GPIIb/llla anragonists include major bleeding, in'- .. . ::h:.rl hcn un hrce u.lJ rhromboc\ ron(nir.

Tleie a{cnts block the plafelet glycoprotein IIb/IIIa receptor,

Class Plarler aggregation inhibitors

Subchss

Generic/trad Name
acetylsalicylic acid/aspirin dipyridamol,4ersrnlin

Tflrditional

Adensosine diphosphate-induced

clopidogrel/Plavix

platelel-fi brinogen binding inhibitors

ticlopidine/Ticlid
Plalelet Slycogen IIb/IIIa inhibitors
ep!ifi bat;de,{ntegrelin

Plarelet-rducing agent

Phosphodiesterase

III inhibitors

anagrelide/Asrylin
cilostazolry]tal

Thrombolytic agents

stieptokinase/Streptase tenecteplase/TNKase urokinase/Abbokinase

. Lepirudin (Reflidan)

. Dznapnord (Orgaran) . Bivalirudin (Ang io m ax)

1&
Copfight O
201 t-2012 -

al Dcks

. PTT (Partiol Thromboplastin Time)

. PT (Prothrombin Time)
. Platelet count

141 Coplaighr O 20ll-2012 - Denta! Decks

These agents are administered intravenously for prevention ofpost-operative deep vein

thrombosis following elective hip replacement surgery; for prophylaxis or treatment thrombosis in adults with heparin-induced thrombocytopenia.

of

Their mechanism ofaction is through the direct inhibition of thrombin within the coagulation pathway, thus inhibiting fibrin formation.

This test is a one-stage tst for detecting certain plasma coagulation defects owing to a deficiency offactors V VII, or X. Thromboplastin and calcium are added to a sample of the patient's plasma and simultaneously, to a sample from a normal control. The length of time required for clot formation in both samples is observed. Thrombin is formed from prothrombin in the presence ofadequate calcium, thromboplastin, and the essential tissue coagulation factors. A prolonged PT therefore indicates deficiency in one ofthe factors, as in liver disease, vitamin K deficiency, or anticoagulation therapy with the drug
coumadin.

International Normalized Ratio (/r'R/. Once prothrombin times are determined, they are expressed as an INR value. INR stands for International Normalized Ratio and essentially is the ratio ofthe prothrombin time measured in the patient divided by a standard prothrombin time value, and multiplied by a constant. An INR value of I means normal prothrombin times ofapproximately l2 seconds; normal blood clotting would be present. INR values greater thar 1 indicate that there is an anticoagulant effect. The higher the INR value, the greater the anticoagulant effect. Many patients taking anticoagulants have INR values of2-3 and even uo through 6.

- All oftle following conditions are manrged by using anticoagutants and \ \-t snti-platelet agents l9xcEPI one. which one is the EXCEPTI0M
. Coronary Artery Disease (CAD)

. Angina Pectoris (Unstable Angina)

. Myocardial Infarction (Heart Attack)

Stroke

. Hypertension

112
Cop)righr O 2011,2012 - Dental Decks

. HPG-CoB Reductase Inhibitors

. HCG-CoG Reductase Inhibitors

. tMG-CoA Reductase Inhibitors

. HCG-CoB Reductase Inhibitors

143
Cop)"ighr O 201l-201? DmialDecls

Anticoagulants such

as

clopidogrel (Plavix)

are nsed in the conditions listed for the

warfarin (Coamadin) and anti-platelet agents such as aspirin and following reasons:

. Coronary artery disease (ClD): will help prevent threat ofmyocardial infarction in CAD patients. . Angina pectoris (anstable angina): will help prevent thrombus from forming within
the coronary arteries.

. Myocardial infarction (MI): drugs that prevent blood clotting have been shown to prevent the threat of future infarcts. . Stroke: will help prevent thrombus from forming thus preventing threat ofa cerebral embolism.
Note: Unless there are other accomparying cardiovascular problems such as those listed above. anticoagulant drugs are not necessary in the treatment and management of hypenension. These drugs do nothing to lower blood pressure.

Coronart artery disease fClD/ is a condition ofnarrol'ing ofthe blood vcsscls oflhc hcarl rcstncting oxygcn flow ro heart musclc. lt has been cor.clatcd with the lcvcls ofblood cholcstcrol and triglyccridcs. Ifnot trcatcd, CAD can
lcad ro mloca.dial infarction (heart mlrrjrizing the threat ofCAD.

otkrck).D

gs such asthc statins, \\'hich

lowerblood cholcstcrol arc cficctivc in

Currcnrl]. six classcs ofantihyperlipidemic drugs arc availablc. and cach class has its own mcchanism tor lot\'cring l::rd 1c\ cls r-ote: Thctwo major lipoprotcins that arc targctcd arcVLDLSand LDLs. Thc primary lipids ofVLDLS ;J. rhc Ingl!ccridcs. \r'hcrcas thc primary lipids ofLDLS arc cholcstcryl cslcrs. Highcr levcls ofLDL incrcasc thc risk rf..rrdio\ascular drscasc, whercas highcr lcvcls ofVLDL incrcasc the risk ofpancrcalitis.

rri.

' H\lG-CoA

Reductase inhibitors: thc cnzymc 3-hydroxy-3-mcthylglutaryl cocnzymc

A (H]tlc-Co,l) rcdnc-

lrrol

,l,frforl. simr'rstatin (ZoLor). flu\sstatin (ar.or, lovastatin (Mewcor) pr^v^st^tin (Prarachol)

is n..ccssary in thc kcy stcp to synthcsizc cholcsterol. When thc "statin" drugs inhibit this cnzymc, cholcsrs nor produccd in thc livcr and blood lcvcls dccrcasc. Thc family of "statin drugs" includc atorvasaatin

and rostt-

r.statin /ar.,r/o,"/.
. Fibric acid derivatites: thcirprimary lipoprotein effect is to dccrcase trigiyccridc andraisc HDL concentrations. Tlc] do fiis by incrcasing lipoprotein lipasc activity, which rcsults in i crcascd catabolism ofVLDL. Examplcs in c:udc gem fi brozi I /lop id) and fenofrbr^te (Tricor) .

. Bile acid sequestrants: thesedrugs bind tobilc acids, bilc acid scqucstrants

increa-sc thc divcrsion ofcholcstcrol ro bilc acid slnthcsis, lowcr intraccllular storcs ofcholesterol, and res lt in crcascd caiabolism ofLDLby the lr\.r E\amplcs include cholestymmine fQuc"stdn), and colesevel^m (WelchoU.

. Other agents: nicotinic acid lrtdcin) ;s bclicvcd to act on a hormonc-scnsitivc lipasc; this lcads to inhibition of rcleasc offrcc fatty acids from adiposc tissuc /@ob,srt. Thc inhibition oflipolysis lcads to reduccd frcc fatly acid
rranspon ro thc liver and thcrcforc dccrcascd syrlhcsis

ofVLDL.
^nd

. Combination products: examplcs includc lovast^tinlni^cin (Adicor)

ezetimibe/simvastatin (l/ttoritt).

. Selectivc cholestcrol absorption inhibitors: ezetimibe /Zsltdl is thc firsl agcnt in a ncw class ofdrugs that appcar to act on thc brush border of intcstinal cpi(hclial cclls. whcrc it sclcctivcly inhibits $c absorption ofcholcs' terol from dictary and biliary sourccs.

Important: The "statin" dnrgs have thc capability to increase the breakdo*'n ofskeletal muscle thereby releasing muscle protein. Ifthc protein overloads the kidneys, renal failure could result. The ert'thromycin drugs
enhance the capabilities ofthc "statins" to cause this effect.It is advisable for patients medicatedwith a "statin" druts nor to be gi\en eryhromycin nroducts.

ACE Inhibltors inhibit the conversion ofinactive angiotensin I to the angiotensin II, a vasoconstrictor.

. The first statement is true; the second statement is false

. The first statement is false; the second statement is true . Both statements are true

. Both

statements are false

144
Coplright
@

2011-2012, Denhl Decks

Whlch of the drugs below can prolong th QT interval of cardiac electrical conduction and thus can lncrease the risk ofcardiac arrhythmias?

. Erythromycin
.lbuprofen

. H]drocodone . Penicillin VK

Azrtbromyctn (Z-Pak)

145 Coplaighr O

20ll-2012 DentalDeckr

Antihypertensiv agents arc classified by mechrnisms otaction: . Diuretics: irclude thiazide and thiazideJike fNd CIJ inhibitors.) such as hydrochlorothiazide (HCTZ) and foop diuretics such as furosemide /Zasi.r/ and brmet aide (Bumer). These drugs inhibit sodium reabsorption in renal tubular cells within the kidney !o cause excess sodium and u nary excretion resulting in
reduced blood volume.

. Beta-adrenrgic receptor blockers (6era-bloct?/sl: rcduce the volume ofcardiac output irlto the circulation resulting in reduce peripheral pressure. Two types: l. Cardiosefective beta-blockefs (bela rreceptor block in heart muscle/: examples includ atnolol (Tenormin). metopfolol (Lopressor, Toprol XL), (Secral), esmolol (Brevibloc) ^ceb\tolol 2. Non-cardioselective (beta I and beta, beta-blockers: examples include nadolol (Corya ), propr^nolol lndera0, tirnolol (Betinol), pellbntolol (Levatol), and sot^lol (BetapaL") *** Note: labetalol Ard ndate) and c^rledilol (Colg) are non-selective beta-blockers that also block
alphar receptors. . Alpha-adrnergic receptor blockers: cause dilation ofarterioles and veins and reduce peripheral vacular resistance.Two tvpes:

L Cardioselective alpha-blockers
dut tl). pf^zosin

l. ir.,

(alpha sreceptor blockert: examples includ doxazosin fcdr"iprcss)^11d,ter,'zosin (Hvtrin). \on-cardioseleclive (alphal and alpha) alpha-blockcrs: cxamples include phentolamine /R?grt-

(Mi

and phenoxybenzamine (Dibe zNline.).

. Angiotensin-converting enzyme inhibitors (ACE Inhibitors), examples includc lisinoprll (P nivil: Zet ti l)- r^fiipril (Altace) and etral^pril (Vdsolec/i inhibit thc convcrsion of inactive angiotensin I to the angiotensin II, a vasoconstrictor. This results in peripheral vasodilation and secondarily, an increase in urinary volumc cxcrction. Both actions result in reduced blood pressure.

. Angiotensin II receptor blockers

l

f/nBt: examples include losartan (Cozaar), \alsartan (Dioand candesaftalr (Atacand). ARBS block the effects of angiotcnsin II by blocking the binding ofangiotensin Il to its receptors. They do not effect bradykinin.
anl . Calctum channel blockers
examples include Verapamil (Calail),
Azem /Cardizen), and nifedipine (Procardia): inhibit calcium entry into vascular smooth muscle causing vasodilation ofcoronary and peripheral blood vessels thus iowering blood pressure.

^mlodipine

lNorvasc), dilti-

is one ofthe drugs confirmed to prolong the QT interval and is accepted ha\ ing a risk ofcausing anhythmias. The QT interval is measured as the time and disrance benveen the Q point ofthe QRS complex and the end ofthe T wave in the ECG traclng. -{ long QT syndrorr.re was first described in the 1950's as a congenital syndrome in\'olving QT interval prolongation and syncope and sudden death. These congenital long QT svndromes were characterized by a peculiar electrocardiographic appearance of the QRS complex involving a premature atria beat followed by a pause, then a subsequent sinus beat showing marked QT prolongation and deformity. This type ofcardiac arrhythmia was originally termed "torsade de pointes" (from the french " t**isting of the points ").

Erlthromycin
as

Erythromycin, an antibiotic used to trat bacterial infections, is considered as having risk of causing torsade de pointes, an unusual adverse reaction for an antibiotic.

Clarithromycin, an antibiotic within the erlthromycin family also causes prolongation ofthe QT interval. Azithromycin, another member of the erythromycin family of antibiotics is not associated with prolonging the QT intewal.

. Antibiotics
. Aromatase inhibitors

. Antimetabolites
. Alkylating agents . Antimicrotubular

1,16

Cop)righr O 20ll -2012 - Denlal Decks

. Chronic leukemias . Lymphomas

. AIDS

. Myelomas
. Carcinomas ofthe breast and ovary

117 Coplrishr O 201 I -20

12 -

Dental Dcks

Exemestane is an irreversible, steroidal aromatase inactivator. It prevents conversion of androgens to estrogens by tying up the enzyme aromatase. In breast cancers where growth is estrogen dependent, this drug will lower circulating estrogens.
Exemestane is used in the treatment ol advanced cancer in post menopausal women whose disease has progressed following tamoxifen therapy.

Letrozole (Femara) worksby

a similar mechanism as above. It is used as

first line treat-

ment ofhormone receptor positive or metastatic breast cancer in postmenopausal women. It is also indicated as an extended adjuvant treatment of early breast cancer in postmenopausal women who have received 5 years ofadjuvant tamoxifen therapy.

The alkJ-'lating agents contain a diverse group ofcompounds which all form alkyl bonds to nucleic acids. All ofthese agents share a similar mechanism of action and mechanism of resistance. The alkylating agents lorm covalent bonds with nucleic acids, and proreins. The N-7 position ofguanine is a common binding site.

Nitrogen ,Vustsrds:
Ilechlorethamine (Marlalget,
Cy-clophosphamide
1C1

rorar/

Chl or ambI'cil (L e u ke r a n) l\telphalan (Alkerat)

Hodgkin's diseasc and oiher lymphomas Lymphomas, leukemias, multiple myeloma, neuroblasloma, retinoblastoma, and cancers ofthe breast and ovary Chronic lymphocytic leukemia Hodgkin's disease and other lymphomas
Several types ofcancer, including brain cancer Several types ofcancer, including brain cancer and Hodgkin's disease Seveml types ofcancer, including brain cancer

Nitrosoureas:
callnustine (BCN U, B iCN U) Cee NU) Sen\usline (Me I hy I - CC N U)

Lomtstine (CC NU,

. Immune modulators . Monoclonal antibodies

. Colony stimulating factors

. Interferons
. Immunosuppressants

1,18

Cop)'right O 20ll-2012, Denral Decks

149 Copldght C 2011,2012 - DenralDecks

These drugs stimulate the production the hematopoietic process.

ofneutrophils and erythroid progenitor cells in

. Darbepoetin alpha: induces erythropoiesis by stimulating the division and differentiation of erythroid progenitor cells. It is used to treat anemia associated with chronic renal failure.

. Pegfilgrastim Qtleulasta):

stimulates the production, maturation and activation of neutrophils. It is used to decrease the incidence of infection by stimulation of granulocyte production in patients with nonmyeloid malignancies.

. Sargramostin (Leukine)z
marrow transDlantation.

is used for myeloid reconstitution after autologous bone

Listed below are the eight classes ofdrugs used in chemotherapy: 1. Alkylating agents - these agents alkylate DNA such that it cannot replicate. Popular agents include Cisplatin and Cyclophosphamide, 2. Anthracyclines these agents destroy DNA such that the cell cannot replicate. Popular agents include Daunorubicin and Doxorubicin. 3. .{ntibiotics - these antibiotics are not used for antibacterial therapy but were specifically designed for cancer chemotherapy. The agent in this class is Dactinomycin. -1. -{ntimetabolites - these agents interfere which selected biochemical reactions necessary tbr cell growth. Popular agents are s-Fluorouracil (5-FU), 6-Mercaptopurine and

\Iethotrexate, 5. -\ntimicrotubular

- affects the microtubular assembly with cells to inhibit cell mitosis. The popular agent is Paelitaxel (Taxol). 6. -{ntiestrogen these agents block the tumors on which estrogen has a stimulatory effect. The popular agent is Tamoxifen (Nolvadex). ? \'inca Alkaloids - these are mitotic spindle poisons. Examples include Vinblastin and
\-incristine.
8. Gonadotropin hormone-releasing antigen - these inhibit gonadotropin secretion, an action \\,hich is effective in reducing certain carcinomas. The popular agent is Leuprolide.

\ote: The anticancer drugs Asparaginase and Interferons do not fall within any category but are used in the treatment ofcertain cancers. Asparaginase deprives tumor cells ofcertain amino acids such that protein production is blocked. Interferons boost the immune system.
Agents used in treating breast cancr: . Antiestrogens: tamoxtfen Q''lolvadex), fulvesttant (Fasloder), andtorcmifene (Fqreston). . Aromatase inhibitors: letrozole /Feuara) and exernestar\e (Aromasi )

. Nausea and vomiting . Hair loss (alopecia) . Blood test abnormahties (low magnesium, low calcium, low potassium) . Peptic ulcers

Changes within the tissues

ofthe oral cavity such

as mucosititis

. Low white blood cells

. Low red blood cells (anemia) .

Xerostomia
Copyighr C
201

lso
1,2012
_

Denrat Dcks

. Renal failure
. Alopecia

. Peripheral neuropathy
. Glaucoma

151

Coplriglu O

201 1,2012, Denlal Decks

Cisplatin is ar\ anti-cancer ("antineoplastic") chemotherapy drug. It is classified as an "alkylating agent."

Remember: Alkylating agents these agents alkylate DNA such that it cannot replicate. Popular agents include Cisplatin and Cyclophosphamide. Notes about cisplatin side ellects (a d dost chemotherapy drugs): . Most people do not experience all ofthe side effects . The side effects are often predictable in terms oftheir onset and duration . The side effects are almost always reversible and will go away after treatment is complete. . The side effects and their severity depend on how much of the drug is given. In other words, high doses may produce more severe side effects. The most common side effects ofchemotherapy are:

. Anemia . Fatigue . Hair loss

. Low WBCS . Xc.ostomia . Mucosititis

lncreased chance ofbruising, bleeding, and infection

. \ausea and vomiting Orher lesr common side effects include:

. Appetite and weight changes . \ene and muscle problems . Dn and/or discolored skin

. Kidney and bladder iritation

. Sexual and fertility issues because ofeffects on reproductive
organs

is a common reaction to cancer chemotherapy. [t is an inflammation ofthc mucous membranes. During chemotherapy and radiation therapy, mucosal tissues begin to desquamate and deleiop into ulcerations. Thc mucosal intgrity is broken and is secondarily infected by oral flora. Palliarive treatment is indicated formucositis. The antineoplastics such as 5-fluorouracil (JFU), methotexate and doxorubicin are commonly associated with the development ofoml mucosihs.

\ot: Mucosititis

Alopecia (hair Ioss) occurs with administration ofmost clremotherapeutic agents one to tlr o weeks after treatment. Other common side effects include GI upset, increased incidence ofinfection (especially Candidias,9, and degeneration of lymphatic tissue. Remember: Most chemotherapy drugs have been shown to be teratogenic in humans and should be avoided by pregnant women.

\ot: \Iethotrexate

mav cause ulceration of the oral tissues.

G0 phase or resting phase S phase

ofthe cell cycle

ofthe cell cycle

. G; phase ofthe cell cycle .

G2 phase

ofthe cell cycle

Coplrjght

152 20ll-2012 , Dsral Decks

. Hydrochlorothiaz ide (HCIZ) . Furosemide (Zasry'

. Spironolactone (l ldactone) . Triamterene (Dyrenium)

copynsht O

201 I

-2012 - Denbl Decks

***

The S phase ofthe cell cycle = DNA synthesis

Antimetabolites

are one ofthe oldest and most important classes ofantineoplastic agents. They attack the cells in the S phase of the reproduction cycle by interfering with the biosynthesis ofthe purine and pyrimidine bases.

Important: Alopecia (hair loss) occtrs with the administration ofmost chemotherapeutic agents one to two weeks after treahrent. Other common side effects include GI upset, increased incidence ofinfection fespecially Candidiasis), and degeneration of lymphatic
tissue.

Remember: Most chemotherapy drugs have been shown to be teratogenic in humans

and should be avoided by pregnant women.

Diuretics are used to trat congestive hcart failure by relieving edema and symptoms ofdyspnea arising liom pulmonary congestion. They are also used to treat h].pertension, and in the management ofedema associated $irh heparic or renal disease. Cetegories of widely used diuretics:

. Thiazides: inhibit sodium reabsorption in th distal portion ofthe renal tubule within the kidney causing increased excretion ofsodium andwater Prototpe agent is hydrochlorothi^zide (HCTZ) Otherexamples include chlorothiazide (Diuril), indapamid. (Lozol), and metolazon (Zarcxolyn). Note: Thes drugs can cause hypokalemia (ab nornally lot level ofpotarsium in lhe blood) ,hponatremia (abnormally loN' level of sodium in the blood)and may increase plasma uric acid. . Loop diuretics: inhibit reabsorption ofsodium and chloride in the ascendiog Loop ofHcnle thus causing increased secretion ofwater, sodium and chloride. Proto0pe agent is furosemide (rasir. other examples (E.1ecfin), nnd torcefiide (Demadat) . Note| These drugs can include bumetanide (B umer), eth^crynic ^cid cause hr?eruricemia, tinnitus, hearing loss, hlponatremia and excessive fluid loss. . Potassium-sprring diuretics: . Sodit|m channel blockers: these agents inhibit sodium reabsorption through sodium channels in renal epithelial cells. This inhibition creates a negative potential in the luminal membranes ofprincipal cells,
located in the distal convolutedtubule and collecting duct. Negative potential reduces secretion ofpotas_ sium andhydrogen ions- Conserve potassium while caus ing diuresis. Thus, no potassium is lost fiom the body as is the case with other diuretics such as the lhiazides and loops- Triamlerene (D)'refiiutfi) and amiloride (Midamor) are examples of this drug group. . Aldostrone antagonists: thes drugs competitively inhibit the aldostercne receptor This causes incrcased amounts of sodium and water to be cxcreted, while potassium is retained Spironolactone dactone) and epleJerone (1aplal are examples.

f,4!

Fixed-dose combination therapy: Dyazide is the brand name for the combination oftriamterene and hldrochlorothiazide filcfz). Tlis product combines the potassium-sparing diuretic with HCTZ for geater eflicacy than eithr on individually.

**

Notei Positive itrotropic dlngs (drugs that make muscle contract more forcefullv) canbe used in the acute trerlment of heart failure, these include dobutamine, dopamine, inamrinone, and milrinone These drugs may be given intravenously to stimulate heart conhactions and help keep blood circulating They are only used temporarily because long-term use shortens life.

Which of the following is a pharmacologie antagonist of aldosterone in the collecting tubule?

. Mannitol (Osmifuol)

. Glycerrn (Glyrol)

Spironolactone (Aldactone)

. Urea (Ureaphil)

154 Coplright O 20ll-2012 - Denral Decks

. Glyburide (DiaBeta) . Vetformin (Glucophage)

. Glipizide (Glucotrol)

. Glinepiide (Anaryl)

155
Cop).right O 201

l-2012

Dental Decks

Potassium-sparing diuretics result in increased sodium and decreased polassium concentrations at the end ofthe distal convoluted tubules. There are two catgories ofpotassium-sparing diuretics:

l. Antagonist of aldosterone in the collecting tubules: . Spironolactone (Aldactone)

Note: Spironolactone has been found to be effective in the treatment of primary aldosteronism. It may be useiul in the treatment of heart failure because hyperaldosteronism is comfironly seen in this condition. 2. Block the sodium channels in the collecting tubules:

. Triamterene (Dyrenium) . Amiloride (Midamor)

***

The most impodant toxic effect of potassium-sparing diuretics is hyperkalemia.

Osmotic diuretics are highly filtered by the glomerulus and exert a solute-induced diuresis in the proximal tubule. They are used to reduce excess edema associated with neurosurgery or traura to the CNS. Examples include: mannitol, glycerin, and urea.

Remember: Carbonic anhydrase inhibitors fi.e., lcetazolamide) arerelatively weak diuretics because ofthe ability of more distal sites in the loop ofHenle to increase theirreabsorption of sodium. Note: Acetazolamide is used to prevent and reduce the symptoms of altitude sickness.

*** Metformin

is classified as a biquanide

Antidiabetic agents or oral hypoglycemic agents are drugs used as adjuncts to dietto treat non-insulin dependent diabetes mellit\rs (tfpe 2 diabetes)that cannot be controlled by diet alone. . SulfonJ-lureas, the first drug group introduced into the U.S. in 1955, close potassium channels in ccll mcmbranes, stimulate the beta cells to produce more insulin., and incrcase the sensitivity oftargeI organs to insulin.

. The original "first gneration " sulfonylureas include tolbnt^mide (Orittdse), tol^z nride (Tolindrel. and chlorprop^mide (Diabinese). These drugs work well in lowering the blood sugat but thel,ha\'e a major drawback. Bccausc they bind to proteins in the blood, thcy can be dislodged by other medications that bind to thcse same proteins. Once dislodged, their activity can increase tapidlr'and lead to low blood sugars. . Second genration sulfonylureas includc glipizide (Glucotol), Elyburide (Micronase) and glimepiride (Amaryl).These drugs have an advantage for those who use other medications since
rhey do not bind to carrier proteins in the blood. Bccause lorr blood sugars are less likely.

ofthis, drug interactions that may

cause

(Glucophage.) primarily decreases hepatic glucose production. It also has minor effects on insulin sensitivity in both the liver and peripheral tissues. It has no direct effect on lhe pancreas and therefore does not enhance insulin secretion.

. Biquanides: metlotfiin

. Thiazofidinediones: rosiglitazone

(Avandia) and pioglit^zone (Actos) increase senstivify in the musclc and liverby improving control ofglycemic utilization. This in tum reduces circulating insulin levels. Notei Functioning beta-cells are required for these medications to work.

. Meglitinides: repaglinide (Prundin)

and oateglinide /Slarllxl lower blood sugar by stimulating the rclease ofinsulin fiom the pancreas in short bursts. Note: Functioning beta-cells a.e required for thcsc medications to work. . o-Glucosidase inhibitors: acarbose fPlcoreJ and miglitol /Gf,set act through inhibition ofpancreatic d-amylase and membrane-bound intestinal cr-glucosidc hydrolase enzymes. This enryme inhibition delays glucose absorption. These enzymes do not enhance insulin secretion

Short-acting insulin with a duration of6-8 hours

. Long-acting insulin with a duralion of20-24 hours

. Intermediate-acting insulin with a duration of l0-16 hours . Rapid-acling insulin with a duration of3-4 hours

't

56

Coprighr C

201

l-2012 - Dental Decks

AII of lhe following are elfects of insulirt EXCEPT one. Which one is the EXCI'PZIO ry

Decreased gluconeogenesis storage

. Increased triglyceride .

Decreased protein s)'nthesis

. Increased glycogen synthesis

157

cop]righr O 201l-2012 - Denbl Deks

Insulin preparations mimic the activity ofendogenous insulin, which is required for the proper utilization ofglucose in normal metabolism. They are used in type 1 diabetes and in type 2 diabetes which cannot be controlled completely by the oral antidiabetic drugs or by diet alone.

Rapid-acting
Insulin aspart (Vovolog) Insulin glulisine (lpi dra)
5-

Onset

Peak

Duration
3-5 hours 3-4 hours 3-4 hours

l5 min

t-3 hours
30-90 min 30-90 min

5-15 min

lnsdin

li spr o (Hum a I o g)

Short-acting lnsulin reg ar (Humulin R) 30-60 min Intermediate-acting

NPH (Humulin N)
2-4 hours 6-10 hours
10-

24 hours

6-8 hours

l6 hours

Long-acting lnsulin detemir lnsulln glar gine

(L ev em i r )

t hour
2 hours

No peak No peak

6-24 hours 20-24 hours

(L an tus )

lmportant: Hypoglycemia (low blootl sagay' is the most serious complication ofinsulin thempy. Symptoms include: sweating, weakness, confusion, slurred speech and blurred vision. Administration ofa concentrated glucose source will relieve mild hypoglycemia.

*** This

is false; insulin increases protein slrnthesis.

Insulin is a pancreatic hormone secreted by the pancreatic beta-cells of the islets ol Langerhans and is essential for the metabolism of glucose and for the homeostasis of blood glucose (it reduces blood glucose by increasing the {onversion to glycogen and -/at. Insulin injection is by subcutaneous administration.
Remember: Insulin is required in treating type I diabetes mellitus because the beta cells of the pancreas are devoid of insulin. In treating type 2 diabetes mellitus, oral hypoglycemics can often be used because the beta cells are able to secrete insulin, although in a more sluggish manner

. Fast onset, short duration

. Slow .

onset, short duration

Fast onset, long duration

. Slow onset, long duration

158 copyrighr O 201l-2012 - Dent.l Decks

. Prothrombin . Fibrin . Heparin

. Plasmin

'|

59

Coplaighr O 201 l,?012 - Dental Dcks

Humulin 70/30 mixture is a popular form ofinsulin that many diabetic patients take. lts
advantage is that after a single injection, the regular insulin component /30o2) provides a fast onset ofblood sugar control beginning one-half hour after injection and the insulin NPH component (702o) starts acting within a couple ofhours to provide a long duration

ofblood sugar control.

Note: Using either agent alone would not provide both the fast onset of insulin action along with the long duration.

Mixtures
Humulin 70130 Novolin 70130
Novolog 70130 Humulin 50150 HumalogT5/25

Onset
30 min 30 min

Peak
2-4 hours 2-12 hours
1-4 hours

Duration
l4-24 hours
Up to 24 hours Up to 24 hours

l0-20 min
30 min
15 min

2-5 hours
30 min

l8-24 hours
2hours

l6-20 hours

Premixed insulins are a combination of specific proportions of intermediate-acting and rapid-acting or short-acting insulin in one bottle or insulin pen (the numbers following the brqnd name indicate the percentage of each 4,pe o./ insulin).

Heparin is contained within mast cells and basophils. These cells occur tn connective tissue and in extracellular spaces near blood vessels.

Remember: Heparin not only neutralizes tissue thromboplastin, but also blocks thromboplastin generation.

\ot6 -

will result in an increase in bleeding time due ro a potentiation of antithrombin III thereby inactivating thrombin. This pre1.

The administration ofheparin

\'ents the conversion offibrinogen to fibrin. ?. It is used for prophyla-ris and treatment of thromboembolic disorders.

. Etanercept (Enbrel)
. Infliximab (Remicade)

. Adalimumab (Humira)

160
Copyright O 2011,2012 - Dental Decks

Tnazolam (Halcion), a pre'operative sedative in dentistry, is metabolized in the liver by the P-450 isoform CYP 3A4 enzyme. Drugs which lnhibit the actions of CYP 3A4 would affect triazolam in which wav?

Cause an increase in serum levels oftriazolam

a decrease in serum levels

. Cause

oftriazolam

Cause no change in serum levels of triazolam

161

Cop'.right O 20Il-2012, Denral Decks

There are currently three tumor necrosis factor alpha (TNF) inhibitors FDA approved for the treatment ofRA (listed in order oftheir approval Jbr k4):

. Etanercept (Enbrel) is used to reduce the signs and symptoms ofactive rheumatoid
arthritis in patients who have had inadequate response to one or rnore disease-modifring anti-rheumatic drtgs (DMARD).It is a recombinant DNA-derived protein which binds to tumor necrosis factor alpha (l'ly'F).

. Infliximab

(Remicade) is used to treat Crohn's disease and rheumatoid arthritis. Infliximab is a chimeric monoclonal antibody that binds to tumor necrosis factor alpha (TNF) thereby reducing the inflammatory actions ofthis endogenous compound.

. Adalimumab (Humira) is a fully human anti-TNF monoclonal antibody with high specificity for TNF. Adalimumab binds specifically to TNF and blocks its interaction with the p55 and p75 cell surface TNF receptors, thereby interfering with endogenous TNF activity. Adalimumab binds to both soluble as well as cell bor.urd TNF. It is administered by subcutaneous injection every two weeks but can be increased to weekly, ifneeded. Adalimumab is effective in RA, Psoriatic arthritis, and ankylosing spondyli-

tis, and Crohn's disease. Tumor necrosis iaclor alpha (TNF) is a pro-inflammatory cytokine produced by macrophages and lymphocfes. It is lound in large quantities in the rheumatoid joint and is produced locally in the joint by synovial macrophages and lymphocyes infiltrating the joint synovium. TNF is one ofthe critical cytokines that mediate joint damage and destruction due to its activities on many cells in the joint as well as effects on other organs and bodv svstems.

\ote:

Triazolam is known to interact with drugs that inhibit its metabolism via the CYP 3A4
enzyme. Drugs that inlibit the metabolic pathway may have a profound effect on the clearance oftriazolam. The resultant effects would be an increase in serum concentrations \\ith an associated unexpected increase in the actions of triazolam. Consequently, triazolam should be avoided in patients receiving very potent inhibitors ofCYP 3,A.4.

-\ntifungaf agents (itroconazole, ketoconazole, Jluconazole, miconazole, voriconazole) can significantly elevate the serum levels of triazolam resulting in toxicity with therapeutic doses. These antifungal agents inhibit the CYP 3A4 isoform responsible for heparic metabolism oftriazolam. Thus the normal metabolism oftriazolam is inhibited.
Do not administer triazolam to patients taking any ofthese antifungal agents.

. Twice

a day

. Every 4 hours . Three times

a day

. Four times a day

162
Copltight
@ 201

l'2012 - Dental Decks

. Pilocarpine (lsopto-Carpine) . Latanoprost

(Xa latan)

. Betaxolol (Betoptic) . Bimatoprost

(L

umiga n)

163 Coplright O 2011,2012 - Dental Deck

Other popular and common abbreviations used when writing prescriptions:

. t.i.d. : three times a day . q.l2.h.: every 12 hours . q.4.h. = every 4 hours . stat. = immediately . h.s. : at bedtime
. p.rn.

. b.i.d.

twice a day

a.c.

as needed

before meals

. h.

= qfrar ma.la

'

Sig. = Label

Note: Always document prescriptions that are given to a patient in the patient's chart, along with the date they were written and any specilic instructions for patient use.

Remember: . I grain = 65 mg

.l

ounce = 30 g or 30

mI

Glaucorna is characterized by an increase in intraocular pressure. It is caused by poor drainage of the aqueoushumor (luid in the eye) and can cause blindness.

. Pilocarpine (1sop to-Carpine)r eye drops in the eyes causes papillary constriction thus allowing for drainage ofthe aqueous humor to reduce pressure . Latanoprost (Xalatan)z a prostaglandin analog; eye drops in the eye reduces intraocular pressure by increasing the outflow ofthe aqueous humor . Bet^xolol (Betoptic): abeta-blocker; eye drops in the eye reduces intraocular pressure by reducing the production of aqueous humor . Bimatoprost fZ, miganl same action as latanoprosl (Xalatan)

'

.,The following drugs are noted for causing what prominent oral slde

effect?

Amrnipqline (Elavil)

. Diphenlydramin e (Benadryl)
. Atropme

. DiazepNn (Valiun)

'|

64

Coprigh

O 201| -2012 - Denbl Decks

. The first statement is true; the second statement is false

. The first statement is false; the second statement is true

Both stalements are true

. Both statements are false

16s
Cop''right O
201 I

-2012 - Dental Decks

Xerostomia can be caused by certain drug classes that inhibit the production and secretion of saliva.

. Amitriptyline (Elavil) is representative of the tricyclic antidepressants, a class of drugs lhat causes significant xerostomia. They probably work through an anticholinergic action. . Diphenhydramine (Bena&yl) is representative olthe sedating-type antihistamines,
a class

ofdrugs that causes significant xerostomia. They probably work through an an-

ticholinergic action.
. Atropine is a powerful anticholinergic which blocks the production of saliva in the salivary glands. Other anticholinergics will have a similar action.

. Diazepam (Vctlium)
\ote:

is representative of the benzodiazepine tranquilizers. These drugs have moderate anticholinergic actions to reduce the outflow of saliva.
The xerostornia actions produced by these classes ofdrugs are reversible with nor-

mal salivary flow regained after discontinuance ofthe drug.

Levodopa is used in the treatment of Parkinson's disease to replenish th brain's supply ofdopamine, the neurotransmitter thal is deficient in this disorder Parkinson's disease i/PD) results from a relative excess ofcholinergic activity and a deficiency ofdopaminergic actilitr in the basal ganglia. It is a chronic, debilitating disease with no kno$'i cure. Drug treatment for PD has cenrered on increasing the availability ofdopaminc in the CNS, inhibiting the effscts ofacetylcholine,
and a$cmpring to prevent further cell mmbmne damage through neuroprotective trials. Note: The D2-recep_ :..r subllTre is lhe p mary modulatorofboth clinical improvment and adverse rcactions such asdystonia and

***

hrllucinations. Lerodopa has been thc single most important drug in the treatment ofPD. Administering carbidopa in combination \r'ilh levodopa fsir?emet, reduces lhe required dose of levodopa by about 75%. when levodopa is grr er alone. much ofrhe dose is metabolized befor the drug reaches the brain. Therefor, large doses are requrf3d. and these are apt to caus unwanted side-effects. Carbidopa inhibits the pcripheral decarboxylation of lerr.dopa. This action simultaneously reduces the likelihood ofperipheml side effecls and allows more lev-

riopa

ro reach the brain. Since carbidopa does not cross the blood-brain barrier, the levodopa in the brain is

conlened rhere to dopamine. Thus, co-administration ofcarbidopa plus levodoPa in the form ofSinemet al_ lo\\s a significant reduction oflevodopa dosage without rcducing the desired effccts. Other rntiparkinson agents: . llfonoamine oridas B (MA)-B) inhibitorsr seleglline (El.lepy, and rasallllne (Azilect).T1rese drugs irreversibly inhibir the enzyme MAO-B, which is responsible for the oxidative deamination ofdopamine in the brain. This causes dopamine to accumulate in surviving nerve cells and reduces the symptoms ofPD . Gfutamate antagonist (anliirury amartadine ($'mmetrel) appearc to potentiate dopamineryic responses. . Dopamine agonists: bromocriptine, pcrgolide, apomoryhtne (Apokrn), pramipexole (Mirupex), and ropinitule (Requi . These d gs are direct dopamine receptor agonists. . Anticholinergic agents (antimuscarinic drugs): benztropine (Cogentin) and ftlhexyphentdyl (Tasmar). These drugs supprcss central cholinergic activity and may inhibit reuptakc and storage ofdopamine in the CNS. rhus prolonging the actron of dopamine. . Catechol-O-methyl t r^osfer^se (COMT) ilhibitorsi tolcapone i1zQsma, and entacapone fcotntan) T1\ese drugs are inhibitors ofCOMT, another enzlme that metabolizes dopamine. . Certain antidepressrnts and antihistamines such as diphenhydramine that have antimuscarinic actions
may be given in the early stages ofdisease.

Which artiarrhlthmic agent is ffectlve only on the ventricle and is often administered IV to trert life.threatening ventricular arrhythmias?

. Quinidine (Quinidex) . Lidocaine (Xylocaine)

. Flecainide (Tambocor) . Propafenone (Rythno I) . None of the above

166 Copyight O 20ll-2012 - Denhl Decks

167
Copt?ight O 20lt-2012 - Denral Decks

When lidocaine is used IV to treat ventricular arrhythmias, it acts on the fibrillating ventricles to decrease the cardiac excitability and spares the atria. It can effectively reverse a life-theatening situation.

Quinidine is considered as the prototype antianh)'thmic agent and is used primarily to treat atrial fibrillation. It is not effective in treating life-threatening ventricular fibrillahon.

Flecainide (Tambocor) is potent antiarrhythmic agent, effective in a wide range ofventricular and atrial arrhythmias and tachycardias. Propafenone (Rythnol) is used to treat both ventricular arrhlthmias and supraventricular tachycardias.

Dr
I

John Doe, DDS

I Any Street Any Ciry, Any stare 00000

(000) 5s5-

License # Federal Drug Registry #

l2l2
Age:
Date:

Patient's Name:
Patient's Ad&ess:

Amoxicillin 500 mg. tablets

Disp. Four (4) tabs
Sig: Take 4 tabs f2000 mg) 30-60 minutes prior to dental appointment

Signature:

Substitution permissible Substitution not permissible Number of refills Notes:

. Inscription ' Name of drug and the strength ofthe drug fi.e., 500 mg tablets) . Subscription - Directions to the pharrnacist (dosage form and amount to be given Disp

. Superscription

Patient's name, address, age, date

. Transcription or signa

. Signature

- Directions to the patient (SigJ Signature of person prescribing medication must appear

All of the following drugs are useful for treating whrt common medical condition?

. Prednisone . Gold injections

. Methotrexate
. Nabrmetone (RelaJbn)

. Piroxicam (Feldene)

168

Coprighr O

201

201? - Derral Decls

Which IIIO gastrointstinal drugs listed below reduce the formation of stomach acid by inhibiting the proton pump of the stomach parietal cells?

. Ranitrdine (Zantac) . Omeprazole (Prilosec)

. Cimetidine (Tagamet) . Famottdine (Pepcid)

. Lansoprazole (Prevaci d)

'|

69
Decft s

Coprdght C

201

l'1012 - Dental

Rheumatoid arthritis (RA) is a chronic inflammatory disease ofjoints that results in joint pain, swelling, and destruction. RA is characterized by chronic inflammation ofthe synovium, which lines the joint. With disease progression, there is the accumulation of
prostaglandins, leukotrienes and other mediators in the inflammatory changes and tissue destruction in the synovial lining.

How these drugs work in treating rheumatoid artkitis: . Prednisone: decreases the inflammatory response . Gold injections: may decrease prostaglandin production . Methotrexate: unknown, but may affect immune function . Nabumetone fRela/en): an NSAID that inhibits prostaglandin synthesis . Piroxicam (Feldene): ar NSAID that inlibits prostaglandin synthests
the above drugs except gold injections are also useful in the treatment of osteoarthritis (OA). OAis characterized by progressive loss of articular cartilage. This may be the result of excessive loads on the joint or other factors. Agents useful in treat ing OA provide an analgesic and anti-inflarnrnatory action to reduce pain within thejoint.

\ote: All of

Hydrochloric acid (l{Cl) is produced by the parietal cells ofthe stomach through a pump u ithin each cell which pumps protons (H.) into the stomach contents. The pump is called tbe H-/K' ATPase pump. HCI is used for food digestion but an abundancy can cause heart bum and acid indigestion. Omeprazole and lansoprazole inhibit the pump such that no protons are pumped into the stomach contents and thus no HCI is produced. These nvo drugs are classified as proton-pump inhibitors.
Stomach acid can also be reduced by inhibiting the effects of histamine in the stomach at the histamine type-2 receptors (H2 receptors). Ordinarily, histamine stimulates the gastric

parietal cells to produce hydrochloric acid. Ranitidine, cimetidine and famotidine block the effects of histamine by blocking at the H2-receptors. These tkee drugs are classified as H2-receptor blockers. Both the proton-pump inhibitors and H2-blockers are used to feat heartbum, indigestion,
sour stomach, active duodenal ulcer disease and gastroesophageal

reflrx disease (GERD).

Remember: Antacids neutralize excess stomach acid by a chemical reaction. Antacids

include aluminum hydroxide (Amphogel), bismuth subsalicylate (Pepto-Bismol), calcium carbonate (Tums) magnesium hydroxide (Maalox) and sodium bicarbonate.

. Heparin

. Vitamin K
. Aspirin

. Cloprdogrel (Plavix)
. Warfarrn (Coumadin)

170
Copyight O 20ll-2012 - Denlal Decks

What serious dental elfect is associrted with the following drugs: (Zo meta), pamidronate (Aredia), risedrontte (A ctonel),, znlendronic ^cid ibandronate @azira) and alendronxte (Fosamax)?

. \4ucositis . Osteonecrosis ofthe jaw bone

. Angular cheilitis

. Oral yeast infection . Xerostomia

171 Cop)righr O 20ll-2012 - Denhl Decks

Heparin inactivates thombin and prevents the conversion of fibrinogen to f:Jc.rin (blood clot);w^rfarin (Coumadin) rnterferes with the hepatic synthesis of vitamin-K dependent coagulation factors lI, VII, IX and X resulting in the inability ofthe coagulation pathway to form ftbrin (blood clot). Vitamin K is a group of fat soluble vitamins that are essential for the synthesis of coagdation factors II, VII, IX and X, and prothrombin in the liver. Vitamin K will enhance blood clotting rather than inhibit blood clotting.

Aspirin inhibits blood clotting by inhibiting platelet aggregation in an irreversible

manner. Inhibition ofplatelet aggregation prevents activation ofthe coagulation pathway; thus no fibrin (c/ot) is formed. Aspirin does not affect the coagulation pathway. Discontinuation ofaspirin for 5 to 7 days allows for normal clotting time to reappear due to the

svnthesis of new platelets.

Clopidogrel /P/avx) inhibits blood clotting by inhibiting platelet aggregation in an irreversible manner. Thus the effects on blood clotting are the same as aspirin. Clopidogrel rPlatix) does not cause gastric ulcers like aspirin does and is the antiplatelet agent of choice in patients with history ofulcers.

\ote: Cfopidogrel, aspirin, abciximab

(ReoPro), and anticogulants (i.e., heparin) are used to lessen the chance of heart attack in people who need percutaneous coronary in-

ten ention fPCl), a procedure to open blocked arteries ofthe heart.

Zoledronic acid (Zometa), pamidronate (Aredia), fisedrci^te (Acto el), ib^odtonate (Bohiw), and alendror.ate (Fosamax) are members ofthe bisphosphonate class ofdrugs used to heat and manage
Pagt's diseas, osteoporosis and to prevent hypercalcemia ofmalignancy. Bisphoshonate therapy has been associated with osteonecrosis, primarily ofthe jaw; this has been observed mostly in cancer patients, but also in patients with postmenopausal osteoporosis and other diagnoscs. Risk factoN include ofcancer, with concomitant chemotherapy, radiotherupy or corticosteroids; anemia, coagulopalh!. infection or pre-existing dental disease. Symptoms included nonhealing cxtraction socket or an
a diagnosis

e\posed jawbone. There is no data addressing whethe. discontinuation oftherapy reduces the risk ofde\ eloping osteonecrosis. However, as a precautionary measure, dental exams and preventativ dentistry should be perlormed prior to placing patients with risk factors on chronic bisphosphonate therapy.

tir

an affinity for hydroxyapatite crystals in bone and act as antitesorpTheir primary mechanism ofaction involves inhibition ofosteoclastic bone resorption. Adr erse effects /6esider osteohecftrsis of the jaw bor) include GI symptoms and esophagcal erosions.

Important: Bisphosphonates have

e agents.

Orher agents that have an effect on bone:

. SERlls fse/ectil,e
. Hormones: . Calcitonin:

eJtrcgen ,eceptor modulatorsl. R^lo\ifeie (Evisla) reduces rcsorption ofbone and decreascs overall bone fumover. It is used for heating osteoporosis.
is a naturally occurring hormone that is produced by parafollicular C-cells in the thyroid gland. It is known to block bone resorption through its potent inhibitory elTects on osteoclasts . Parathyroid hormone: PTH is the primary regulator of calcium and phosphate metabolism in bone and kidney. Physiologic actions include regulation ofbone metabolism, renal tubular reabsorprion ofcalcium and phosphate, and intestinal calcium absorption. Once-daily adminishation of P'lH (tefiparatide IForleol) stimulates new bone formation via preferential stimulation of osteoblastic activify over osteoclastic activity. Note: PTH also acts on th kidneys by reducing renal clearance ofcalcium which increases plasma calcium. It also stimulates the production ofthe active form of vitamin D in the kidney. . Vitamin D: helps to ensure that the body absorbs and retains calcium and phosphorus. which are critical for building bone. Note: 1,25-dihydroxycholecalciferol is the biologically active form ofvitamin D (Cholecalciferol)

. Plasmin . Lysozyme
. Renin . Heparin

172 Coplriglt O
201 1-201 2

- Dental

Deck

. Nicotine abuse . Ethanol abuse

. Opioid

abuse

. NSAID abuse

'|

73

Copyriglt O

201 I

-2012 -

Dsral

Decks

Renin is proteolytic enz)'rne produced by and stored in the juxtaglomerular apparatus

that surrounds each arteriole as it enters a glomerulus. Renin acts on the precursor substance angiotensinogen, which is manufachrred by the liver and is present in the blood. Renin converts angiotensinogen to angiotensin I. In turn, angiotensin I is converted to angiotensin II by a converting enzyme associated with the walls ofcapillaries, particularly in the lungs.

Important: "The converting enzyme that converts angiotensin I to angiotensin II known as angiotensin converting enzyme or ACE."
Angiotensin

is

II is a potent vasoprssor. It not only increases total peripheral resistance but, by stimulating aldosterone release, leads to an increase in plasma volume, venous retum, stroke voh.rme, and ultimately an increase in cardiac output.
\ote: Aliskiren (Tehuma)
is a renin inhibitor used to treat hypertension. This is the first ofa new class of drugs and little information is available. It is used alone or in combination with other agents for the treatment ofhypertension.

Disulfiram is not a cure for alcoholism but is a deterrent to ethanol consumption. Disulfiram is an antioxidant that interferes with the hepatic oxidation ofthe acetaldehyde metabolized from alcohol. Specifically it inhibits aldehyde dehydrogenase, a mitochondrial enz]'me found in the liver Even the ingestion of small amounts ofethanol results in high
concentrations ofacetaldehyde in the body. The unpleasant reaction that occurs (called the Disulliranr-Ethanol Reaction or DER) consists ofa throbbing headache, dyspnea, throbbing in the neck, nausea, copious vomiting, thirst, tachycardia and hypotension. \ote: lletronidazole, also inhibits aldehyde dehydrogenase.

Ethanol is

a sedative-hypnotic drug and is the most important alcohol ofpharmacologic

interest. Its abuse is responsible for many socioeconomic problems. Drugs that are synergistic with ethanol include diazepan, meperidine, pentobarbital and chlorpromazine. When combined with alcohol these drugs could cause fatal oversedation.

Remember: Synergism refers to the combined action oftwo or more drugs that is greater

than that achieved with a single drug.

. The first statement is true; the second statement is false

. The first statement

is false; the second statement is true

Both statements are true

. Both statements are false

174
Coplrighr O 201 I -20 l2 - Denral Decks

. Anaphylaxis . Heart attack

. Syncope . Urticaria

175
Copraight O 20l l-2012 - Dental Decks

Gastric antacids are drugs that directly neutralize the gastric acrd (HCL) secreted in the stomach. Antacid therapy is directed at decreasing the concentration and total load ofgas-

tric acid.
Some common over-the-counter antacid products:

. Sodium bicarbonate
- Alka-Seltzer

products.

. Calcium carbonate products:

- Amitone

- Tums

. Aluminum hydroxide products: - Altema GEL - Amphojel

. Magnesium hydroxide products: - Milk of magnesia . Bismuth salt products:

- Pepto-Bismol

. \Iagnesium and aluminum products:

- Maalox - \4ylanta

is the most potent of these but has less neutralizing capacity than calcium carbonate or sodium bicarbonate.

*** Aluminum hydroxide

Note: Dyspepsia means an impairment ofthe power or function ofdigestion.

Inlaled ammonia irritates trigeminal nerve sensory endings, with a resulting reflex stimulation of medullary respiratory and vasomotor centers. An aromatic amrnonia vaporole

oforlgen rrrll aid

is crushed betrveen the fingers and held near the patient's nose. Note: The administration in combating tissue anoxia.

The sl mptoms of syncope include beads ofsweat on the upper lip, a weak thready pulse, cold clammy skin, pallor and a dizzy feeling. The loss of normal vasomotor tonus produces pooling of blood peripherally so that the normal blood volume becomes insufficient. Placing the patient in a supine position and elevating th feet gives the patient a transf'usion ofwhole blood by utilizing the forces of gravity. Note: The head should not be more than about 10 degrees lower than the rest ofthe body.

Tl pes of syncope:

. Vasor agal ) . \eurogenic Trear uirh high-flowing 1007o oxygen I . C)nhostatic -f . Hyperventilation syndrome Oxygen is not indicated

Note: 100% oxygen is contraindicated for

tive pulmonary disease (COPD).

a person who suffers from chronic obstruc-

. Growth Hormone
. Insulin
. Antidiuretic Hormone (ADH)

. Epinephrine

176 Coplright
@ 201 I

'2012 - Dental Decks

. Dopamine

. Aldosterone . Vasopressin . Somalotropin

177

coplrighr O 20ll-2012 - Dnhl D@ks

ADH is a hormone that decreases the production of urine by increasing the reabsorption of water by the renal tubules. Without ADH, there would be extreme loss of water into the urine. Ethanol (ethyl alcoftoi) inhibits the production ofADH.
Remember: Ethyl alcohol dilates blood vessels of the skin, depresses the CNS, and in blood levels in excess of400 mg o/o usually results in coma and death. Alcohol acts primarily on the nerve cells within the brain. Alcohol interferes with communication between nerve cells and all other cells, suppressing the activities of excitatory nerve pathways and increasing the activities of inhibitory nerve pathways. Note: Recent evidence has shown that ftequent ingestion of moderate amounts ofalcohol in any form (beer, wine, distilled spiits) will reduce the risk of heart disease, particularly in men.
The order in which alcohol affects the various brain centers is as follows:

. Cerebral cortex . Limbic system . Cerebellum

. Hypothalamus and pituitary gland . Medulla lbrain stem)

Grorlth hormone (GI{) is produced by, and secreted from the anterior pituitary gland.
Basic Metabolic effcts of growth hormone: . Increased rate ofprotein synthesis in all cells ofthe body . Decreased rate ofcarbohydrate utilization thoughout the body . Increased mobilization offats and use of fat for energy

Human growth hormone is prepared commercially and used as replacement therapy in patients with growth hormone deficiency. The commercial preparation is prepared as the purified polypeptide hormone of recombinant DNA origin with the same amino acid sequence as that produced by the pituitary gland. Human growth hormone is indicated in children for the treatment of growth failure due to lack ofadequate endogenous growth hormone secretion. It has been used in adults who have a growth hormone deficiency as a result ofpituitary disease. Note: Human growth hormone is adminislered as subcutaneous injection or intramuscuIar injection, usually tbree times per week.

. Colchicine
. Indomethacin

. Sulfinpyrazone
. Probenecid
. Allopurinol

178 Coplriglt O 20ll-2012 - Dental Decks

. Epinephrine
. Norepinephrine

. Chlolpromazine

. Isoproterenol
. Dopamine . Dobutamine

179
Copyright O 20ll-2012 - Dnral Decks

The therapeutic management of gout involves three different aspects ofthe disease: l. Reducing the inflammation during acute attacks: The drug ofchoice is colchicine. Colchicine impairs leukocytic migration to inflamed areas and disrupts urate deposition and the subsequent inflammatory response. It is most effective when initiated 12 to 36 hours after symptoms begin.

Notes: l. Colchicine should never be given IM or subcutaneously (it causes tissue irritation). 2. Colchicine can severely damag the liver and kidney; long-term therapy may cause bone marrow depression.

Remember: NSAIDs are also important for the treatmenl ofacute gouty arthritis. Indomethacin (rzay cause renal damage or bone maruow depressiar) is most commonly used.
2. Decreasing uric acid production: Allopurinol (Zyloprin) is the drug ofchoice in the management ofchronic gout. It inhibits xanthine oxidase, an enzyme that converts hypoxanthine to xanthine, and xanthine to uric acid. May cause GI disturbances.

3. Enhancing uric acid clearance: Uricosuric agents include probenecid (Benemid) and sulfinpyrazone (Anturane). These agents act primarily in the kidney (.yecifcally, the proxintal convoluted tubules) and inhibit the secretion of other weak acids (i.e.. penicillin), in addition to inhibiting the reabsorption of uric acid. Remember: Normally penicillins and cephalosporins have to be given in high and frequent doses due to their high rate of elimination by the kidneys. Their excretion is slowed by giving probenecid.

*** Chlorpromazine

is a dopamine antagonist and antipsychotic agent.

Catecholamins are any one ofa group of sympathomimetic compounds composed of a catechol molecule and the aliphatic portion ofan amine. Some catecholamines are produced naturally by thebody (called endogenous) andftnction as key neurological chemicals (i.e., epinephrine, norepinephrine and dopamine). Note: Epinephrine, \orepinephrine and Isoproterenol are considered to be direct-acting catecholamines.

Drug Epitrpkine \orepinephrine

Clinical ApplicatioDs
Anapbylaxis. glaucoma, aslhma, to caus
To cause vasoconstriclion in h)?otension

Commnb Stimulat
s th

myocardiun

Stirmlatcs thc myocardium

Dopamine Dobulamin

Shock, head failure Shock, hean failure

lmfirdiaia

precursor of NE

Dng
(Not Catcchol4nine) Amphctsmin, phEnmeirEine Ephedrine Pherylphrine Albuterol. nelaDrolercnol te6utaline Narcolepsy, obsiry, attenrion deficit disorder Urinary inconlinence, to cause vasoconstriction,
decongestion

Tocau\e m)dria,is. rasocon.tricrion. decongesrion

Asthma, prmature labor
To cause nasal decongestion (long

Or},lnet ?oline. xylomlazoline

acting

. Methocarbamol

(Ro b axin)

. Cyclobenzaprine (F lexer i l) . Baclofer (Lioresal)

. Slccinylcholine

(Anectin e)

. Carisoprodol (,Sozc)

180 Cop)'right O 20ll-2012 - DentatDecks

. Levodopa (Dopar) . Bromocriptine (Parlodel) . Pergolide (Permax) . Halopeidol (Haldol) . Selegiline (Eldepryl) . Amantadine (Synmetrel)

181

Copyright O 2011,2012 - Dental Decks

*** Succinylcholine

is the prototype depolarizing neuromuscular blocking drug.

Spasmolytic drugs (skeletal muscle relax4,l/t are agents that relieve muscle spasms without paralysis. They act in the CNS or in the skeletal muscle cell mther than at the neuromuscular end plate. These drugs are used in certain chronic diseases ofthe CNS (i.e., multiple sclerosis, cerebtal palsy, cerebrovascular accidents) that are associated with painful muscle spasms. By reducing the spasms there is a reduction in pain and improved mobility for the patient. Drugs used for chronic muscle spasm:
is a derivative ofGABA; its site ofaction in reducing muscle spasms is the spinal cord. It stimulates CABABreceptors that are linled to the G protein. Gt, resulting in an increase in K conductance and a decrease in Ca,' conductance. Used is the treatment of mriltiple sclerosis and other spinal cord diseases. All ofthe other skeletal muscle relaxants do not bind to the GABABrecepto$: Diazepam (Valium) and tizanidine (Za aflex) also act rn the spinal cord and are effective muscle relaxants. . Carisoprodol fsoranJ: is used in the treatment ofmuscle spasms and pain associated with acute temporomandibularjoint pain. lts precise mechanism ofaction is not clear but many effects have been ascribed to its central deDressive action.

. Baclofen (Lioresal):

Drugs

Lrsed

for acute muscle spasm:

. C!clobenzaprine (Flexeril): relieves muscle spasm through a central action, possibly at the brain stem level. lt is used to relieve acute, painful musculoskeletal conditions. It is not efllctir e for muscle spasm secondary to cerebral or spinal cord disease. . \lethocarbamol (RobcLrin): is a centrally acting muscle relaxant that is used to relieve
acute. painful musculoskeletal conditions and in the management oftetanus.

\ote: Quinine

is widely used for the effective relief of noctumal leg cramps.

*** Haloperidol

is used to treat psychotic syndromes.

J* g. . Le\ odopa /in couhi ation tith carbidopcJ is the precursor of dopanine. lt is the main treat_ ment 1br Parkinson's discase. It is given with carbidopa to incrcase effectrvcness and rcduce
or pergolide are dopamine agonists which are often given in addition to lev_ odopa earlv in the treatmcnt to enhance levodopa's action, or may be given laterwhen levodopa,s iid. eft'ects become more ofa problcm. ' selegiline is a selectivc inhibitor ofMAo rype B. the enzyme that is rcsponsible for the oxrdatir c deamination ofdopamine in the brain. It is used as an adjunct to levodopa. '-\mantadine appears to potentiate dopaminergic responscs. Antiparkinsonian actions are unrelated to thc antiviral cffects. lt is used in thc early stages for mild diseasc. ts an.l anti_

Parkinson's disease is a slowly progressing, dcgenerative disorder of the nervous system. It has ie\craf distinguishing chamcteristics: tremor (shaking) when at rest, sluggish initiation ofmove_ mcnls and musclc rigidity. ln Parkinson,s disease, nerve cclls in the basal ganglia degcneratc! re_ sultine in lo* er production ofdopamine, ll may be trated fbr ot cured)with a wide varietv of

. Bromocriptine

ride ellects.

. Antichofinergic drtgs (benztropine and ttiheryphenidyl, certaitl .uttidepressa

hi<tunrines such as diphenhydranine) may be given without levodopa in thc early stages ofdis_ ease. $ilh lcvodopa in later stages.
1.

\otrs

Dental implications ofAnti-parkinson's agents;

agents (mai y levodopa, the direct dopamine dgonists and the COMT inhibitors) have been associated wilh orthostatic hypotensior. . Xerostomia lcarsed by a ticholinetgics antl MAO_B inhibitorst. . Schedule appointmcnt times based on when the patient is feeling the bcst. . Dyskinesia (abnonnul muscle movenents) caused by some ofthe drugs (nainly let,_ odopa, the direct dopamine agonist.s, and the COMT ir*ibito,"t can prescnt a chal_ lenge whcn trying to perform dental treatmcnt.

. Anti-Parkinson's

. Caffeine . Doxapram (Dopram)

. Phenobarbital . Methylphenidate

. Phendimetrazine . Strychine

142
Copyright O 20ll-2012 , Dnial Decks

. Feelings of anxiely

and nervousness

Sleep disruption

. Coughing

. Irritability
. Diuresis

Stomach complaints

. Palpitations and arrhlthmias

183 Cop)right O 2011-2012 - Dental Deks

*** Phenobarbital

is a

barbiturate (sedative-hypnotic).

CNS stimulants are a heterogenous group ofcompounds that produce various degrees of stimulation. Analeptic is a term that refers to a CNS stimulant which has the ability to overcome drug-induced respiratory depression and hypnosis. In the past the CNS stimulants were widely used therapeutically, but today they have only limited clinical application. Note: Their use for respiratory depression caused by an overdose ofCNS depressants is generally not safe or recommended.

Analeptics and respiratory stimulants: doxapram and strychnine. These agents have limited use, but are occasionally indicated to stimulate respiration when a patient has pulmonary disease or to hasten recovery from a general anesthetic.

Xanthines include caffeine, theophylline and theobromine. These stimulants improve mental alertness. reduce the urge to sleep and elevate the mood. Caffeine is the only approved OTC stimulant. Theophylline and theobromine are weaker CNS stimulants than calleine. Theophylline is the only xanthine important in the treatment ofasthma. It stirnulates the respiratory centers ofthe medulla and is able to cause bronchial dilation in patients $'ith asthma. Note: It has a low therapeutic index and its metabolism is affected
b1 ser eral other drugs. Sl mpathomimetic amines include the amphetamines and other related agents fi.e., nerh.rlphenidate, phendimetrazine, etc). They are potent CNS stimulants. They are used ro treat narcolepsy, obesity and attention deficit disorder.

Caffeinism is a term used for people who are dependent upon catTeine (i.e., sulfer side efects li'ctn hating too much calfeine, tdke l.tryer"amounts and neetl to keep drinking calfeine to function properll).lt is thought to occur ifyou have an intake ofabove 600 to 750 mg ofcafterne per day /rrore than 10 cups of coffeel. Drinking more than 1000 mg per day is well into :he to\rc range.

Important: Caft'eine stimulates the CNS unequally, with the cortex being the most and the
:oinal cord beine the least excited.

All of the following drugs on the right are used to treat what condition?
. Dexmethylphenidxte (Fo calin) . Extended-release methylphenid|te (Concefta) . Mixed amphetamine salts (Adderal) . Atemoxetine (Str att eru) . Controlled-delivery methylphenidrte (Metadate CR) . Lisdexamfetamine (Vyanse)

. Insomnia in adults

. Tourette's

sy,ndrome in children

. Attention deficit hyperactivity disorder (ADHD)

. lnsomnia in children
184

Copltight O 20ll-1012 ' Dental Decks

PIIARMACOLOGY

Which of the following drugs is a mernber of the opioid family and reduces GI motility ?

. Loperamide (Imodiun)

. Lorazepam (Ativan) . Diphenoxylate and atropine (Lonotil) . Propranolol (hderal)

185 Cop)right
aO

201

201? - Denral Decks

Drugs used to treat ADHD:

. Methylphenidate (Ritalin)z arnrld central nervous system stimulant. In children with ADHD, this drug results in an increase in attention span, reduction in hyperativity, and
an improvement in behavior.

. Dexmethylphenidate (Foc in): a form of methylphenidate called dexmethylphenidate. . Adderal (dextroamphetamine): the brand name for mixed amphetamine salts which act the same as methylphenidate in treating ADHD. . Atemoxetine (Struttera)t the brand name for atemoxetine, the first non-stimulant approved for treating ADHD. It is approved for use in children and adults. . Metadate CR: the brand name for a controlled-delivery methylphenidate, another long acting form ofthe drug. . Lisdexamfetamine (Vyvanse): Lisdexamfetamine is a prodrug; after adminishation it is converted to dextroamphetamine (Adderall) in the rntestines and/or liver. The dextroamphetamine, an amphetamine and stimulant for the brain, is responsible for the effect of lisdexarnfetamine in ADHD.

. Extended-release methylphenidate (Concerlq):

idate.

a long-acting form of methylphen-

Antidiarrheals:

' Opiate

and opioid derivatives

- Loper

L Is an anti-diarrheal which acts on intestinal musclcs to inhibit pristrlsis. 2. Is a member ofthe opioid family. It does not penetrate the cenffal nervous system like the opioids such as codeiner thus it can b sold ovr the counter. J. IIas no vidence of drug abus or dependence (utllike other opioicls such os codeine, morphine
dnri neperidine).

^mide

(I m mod iu m) |

- Diphenoxt-late is an anti-dianhal and inhibits excessive GI tract motiliry and Gl propulsion. Commercial prcparations contain a sub-therapeutic amount ofatropine to discourage abus. Diphenoxylat and. atropine (Lomatil), unlike loperamide flrrodiu,rr, rcquires a prescription. . Antisecretory:bismuth st$sahcylate (P epto-B . Adsorbents: attapulgile (Kaopectate)
is mo

I)

Rmember: Laxatives act in the revene manner ofthe anti-diarrheals and increase the motility of the CI ..aci. Tle] are used to trcat constipation. Examples include: magnesium hydroxide (Milt ry'Magnesid), c sror oil. \letamucil and methylcellulose.

Antiemetics:actonthc'vomitingcenter"inthemedulla-Thiscenterhasfourdifferentsourcesofstimuli.Thc
.hemoreceplor rrigger zone (CTz) is located outside the blood-brain barrier near the vomiting center in the medulla. It communicares with th vomiting center after input is received from drugs and hormones. The
classes

of antiemetics are: . Antidopaminergic:

. Phenothiazines: prochlorpcrazine (Conqazi ne) a'nd prcmelhazioe (Phenerydn) . Benzamidesi metoclopramide /Re8/dnl and fiimcthobenzamide HCL flgdnl
. Anticholinergics:
. Antihistamines: meclizine (Antivert), dimenhydrln te (Dramamine), and scopolamine A/arrderTrtScop)

. Serotonin 5-HT3 receptor antagonists: HCL fj$,t/i, and palonosetron (,4/orl)

ond

^t\sgtron

HCL (Zotan), dolasetron (Anzemer, granisetron

. Initability

. Xerostomia . Loosened teeth . Gum disorders . Sluned . Tremors

speech

186 Coptright O 20ll,2012 - Dental Decks

Of the amino acid neurotransmitters listed below which one is an excitatory neurotransmitter?

. Glycine . Glutamate

. GABA

(y -eminobutyric acid)

. None ofthe above

147 Coplright O 20ll'2012 - Dmral Decks

***

Excessive saliva is a prominent toxic effect ofmercury not xerostomia

of the chronic form, which results from the inhalation of the vapors ofdust ofmercurial compounds or from repeated ingestion ofvery small amounts. The presence of mercury in the body is determined by a urine test. Treatment may include gastric lavage with milk and egg white or sodium bicarbonate, chelation with British antilewisite (BlI), and fluid therapy.
Not: British Anti-Lewisite (BAL) or Dimerc prol and pnicillamin are two drugs currently marketed for promoting the excretion of mercury, lead, and several other agents. A few additional agents are available for the treatment of poisoning by metals other than mercury

These symptoms are all

k.9., edetote colciunt disodium for lead and deferoxamine for iron). Mercury that is absorbed into the circulatory system may be deposited in any tissue.
Higher-than-average accumulations occur in the brain, livel and kidney. Mercury does not collect irreversibly in human tissues. There is an average half-life of 55 days for transport through the body to the point of excretion. Thus, mercury that came into the bodl years ago is no longer present in the body.

foftr' .., ,._ :,

Children and adults wbo are to be treated for lead poisoning should only be given the Edetate Calcium Disodium (Calcium Disodium Versenate) form of

l.

"EDTA."
2. Penicillamine is also a highly effective chelator ofcopper and is ofprimary im-

portance in the management of Wilson's drsease Thepatolenticulqr degeneratiotr). 3. Deferoxamine is a drug that chelates to absorbed iron very well and is eliminated in urine. 4. For carbon monoxide poisoning the fteatment is 100%o oxygen therapy fzvolves breathing oxygen thxtugh a tight-ftting uask). 5. Cyanide poisoning can be treated with rapid oxygen administration and the antidotes sodium nitrite and sodium thiosulfate.

Chemicals that ransmit the signal from one neuron to the next are called neurotransmitlers They are synthesizcd in the ccll body or nen'e terminal of the prsynaptic neuron. Neuroffansmitters are rcleased from thc s\napse and cross the synaptic cleft. The dndrite on the nerve cell body receives the signal. Various receptors on the posts!naptic membrane ofthe dendrite accept only certain neurotransmitte$.

the brain. 30 differcn! neurotrarlsmitters have been classified as amino acids, amines, and neuropeptides.

. Amino acid neutofransmitters: - Glutamate, GABA, and glycine. Glutamate is an excit|tory neurctransmitter. GABA and glycine are inhibitort neurotransmitters. GABA is the major inhibitory neurotransmitter within the CNS. - Include the catecholamins

histamine, and acetylcholin,-dopamine,

norepinephrin, and epinephrine

-as

well

as

serotonin,
gas_

. \europeptides are also hormones; these include vasopressin, oxytocin, insulin, somatostatin, trin. substance P, -most endoryhin, and enkephalin. Remember:
.

Acetltcholin: effects in CNS generated by interaction with a mixture ofnicotinic and muscarinic
a

recep_

lors

. Dopamine:

catecholamine which acts thrcugh at least two subt?es D7 (activates aden![

c\'c|ot"r,r,

(inhibits adenyl cjclase)

. serotonin:
1.

is s-hydroxytryptamine which works through at lcast 14 subreceptor "trtPtominergic" OTe

Biosynthetic pathway

ofACH:

(l) Choline (taken up into nenevia action ofpermease) Stp (2) Choline acetylcholinesterase catalyzes the synthesis of Ach liom acetyl CoA and choline
Step

2.Biosynthesis of NE and

E:

Step (1) Tyrosine to DOPA (enzyme is tvrosine hvdrorylase Step (2) DOPAto Dopamine (enzlme is aromatic L-amino acid decarborylase) Step (3) Dopamine to NE (enz-vme is dopamine bela h)dro\lase) Step (4) fnorlb in the ddrenal nedulla): NE ro E lenzvme is phen ethanolamine N-meth translbrase)

Oral contraceptives block ovulation by inhibiting which ?TrlO antrior pituitary hormones below?

. Follicle stimulating hormone

. Growth hormone (GII)

(FS11)

. Th).roid stimulating hormone (TSll)

. Luteinizing hormone (I11)

. Adrenocorticotrophic horrnone (ACTH)

188 Coplrighr o 201 1,201: - Dental Decks

. The first statement is true; the second statement

is false

. The first statement is false; the second statement is true

. Both statements are true . Both statements are false

189 CoplriSht O 20ll-2012 - Dental Decls

In addition to the above effects, oml contraceptives produce altemtions in the genital trac! including changes in cervical mucus, rcndering it unfavomble for sperm penetration even if owlation occurs. Changes in the endometrium may also occur .endering it unfavorable for nidation (lnrp lantotion of the -fertili.ed owm). Esttogens and progesterone-like compounds (p/ogertrrs) are used for oml contraception.

. Estrogens: are a group of chemically similar steroid hornones. In humans, estrogens are made primarily in the female ovaries and in small amounts in the male testes and the adrenal glands, brain, and fat ofboth sexes. Estradiol is the most abundant and potent natural estrogen in humans. Other gstrogens inlcude ethinyl estradiol and mestranol. . Progestins: ar a gloup of chemically similar steroid homones as well. In humans, progestins are made primarily in the female ovaries and male testes. Progesterone is the most abundant and potent progestin in humans. Other progestins include levonorgestrel, rorethindrone, medroxyprogesterone,
norgestimate and norgestrel.
Types of oral contracptives:

. Combination: oml

contraceptive agents usually contain both an estrogen agent and a progestin agent. Combination drugs include:

. ethinyf estradiol . ethinyl estradiol

. thinyf

and norethindrone fovcor 50, Brevicon 21, and Modicon 28) and fevonorgestrel fPolria 0.15/30, Alesse 28 and Aviane 21) estradiol and norgestrel (Cryselle, Ovral, and Oryestrel)

. Progestin-onfy: nor fiindrone (Micronor) . Emergency contrrception: levonorgestrol (P/dn B) \\'ernings/Prccautions with OIal Contraceptives:
. Tle risk of cardiovascular side effects increases inwomenwho smoke cigarettes, especially those who are
>.15 .veaN

ofage.

. May increase the risk ofthromboembolism. Women with h)?ertension shouldbe encouraged to use anonhormonal folm of contraception.

\ote: Antibiotics have the potential to diminish the effectiveness oforal contraceptives. Advise patients to use additional method ofbirth control when taking antibiotics and oral contmceptives concunently.

the blood stream by binding to albumin protein, which is abundant in plasma. In this way, drugs can be carried to all the tissues and organs. A dmg which is bound to plasma albumin always has some fraction which is not bound. The unbound portion is free to leave the blood compartment to be taken up by tissues where the drug will elicit its pharmacological ellect. The remaining bound fraction of drug then aontinuously releases more free drug to be taken up by tissues. Eventually all drug in the blood compartment will be taken up by this process.

*** Most drugs travel though

lmportant: Interactions betwen two or more drugs can occur ifthey compete for binding on the plasma albumin. If drug A is bound to albumin prior to the patient taking drug B, and drug B has a geater binding affinity to albumin than drug A, then when drug B is taken, it will displace drug A from albumin to result in large amounts ofunbound drugAwhich could lead to adverse reactions due to the sudden large amounts gaining access to the tissues.
One ofthe most fundamental aspects of drug action is the relationship between dose administered and the effect obtained (drugs are dose dependent), Dose and response are related and can be represented by a dose-response curve. There are two basic types ofdose-response curves:

. The graded dose-response (Dn, curve plots the degree ofa given response against the concentration ofthe drug. These curves are useful for determining characteristics ofagonists and antagonists. . The quantal dose-elTect curve: In this case, a given quantal eIlect is chosen (e.9., .t certain degree of cough suppression), and the concentntion ofthe drug is plotted against the percentage of a specific population in which the drug produces the effect. The median effective dose (8D50 or the dose at which 50%o of the individuals exhibit the specifed quantal effecr) and the median lethal dose (2D50 or the dose at which death is produced in 50'% oJ the expelimental animals in preclinical sludies) canbe estimated from quantal dose-eIlect curves. With this tlpe of curve, the relative effectiveness ofvarious drugs for producing a desired or undesired effect, as well as the relative safety between various drugs, can be determined.

What are four criteri| to consider when selecting atr analgesic agent for a patient?

. Type ofpain
. Location ofpain

. Age ofpatient .
Sex ofpatient

. Patient's weight . Concurrent medication . Pregnancy

t 9{)

Coplrighr O

20ll

2012 - DentalDecks

Z'\

Which of the following competitively blocks vitamin K-binding sites .nd inhibits the synthesis of vitamin Kdependent coagulation factors VII, lX,X, andll (prothrombin) and anticoagulant proteins C and S?

. Heparin

. Warfarin (Coumadin)
. Aspirin
. Anagrelide

t 9.t

Coplriehr O 201l'201? - Dental Decks

Criteria considered when selecting an analgesic agent: l. Type ofpain:

. Severe . Mild
. Moderate 2. Ag ofthe patient:

. Infant

. Child .f function must . Adult

When calculating dosage, the height, weight, body surface area and renal hepatic be taken into account

. Elderly: drug response is affected by age-related changes in physiology and pharmokinetics 3. Corcurrent medications: Consider unwanted interactions, especially with the elderly. 4. Pregnancy: Because virtually any drug a pregnant womar takes can cross th placenta and enter the fetal circulation, drug use in pregnant patients is a source of special concem (clrcck with patient s OB/GYN).
FDA Rating System for the Tratognic Effcts of Drugs: The FDA, the govemmnt agency that ovemees the safety ofdrugs, provides the most widely used system to grade the teratogenic effects ofmedications. The FDA assigns a safety category for medications by using a slefter system: A, B, C, D, and X, with A being considered the most safe. X category medications: Studies in animals or humans have demonstrated fetal abnormalities or there is positive evidence of fetal risk based on adveme teaction reports from investigational or marketing experience, or both, and the risk ofthe use ofthe drug in a pregnant woman clearly outweighs any possible benefit (/or example, safer tlrugs or otherfotms of therapy are available).

At therapeutic levels, warfarin decreases liver synthesis of vitamin K-dependent clotting factors by 30o% to 50olo. These clotting factors have different half-lives. Factor WI has the shortest halfJife {6- t hr) vs. factor lI andx (up to 72 hr). Oral anticoagulants do not reverse ischemic damage or lyse an established thrombus but rather prevent extension ofthe existing thrombus and the formation ofnew thrombi by blocking synthesis of clouing
factors.

Oral anticogulants are used after a myocardial infarction to prevent coronary occlusion, in the treatment ofpulmonary embolism, and in the treatment ofvenous thrombosis.

l{ote: Enhanced anticoagulant effects are seen when these drugs are combined with aspirin. For this reason, use acetaminophen (Tylenol) for pain control.
Patients on anticoagulant therapy may have excess bleeding after dental treatment.

Al-

ways check medical history. If patient is on anticoagulants, his/her physician should have documentation of INR values to assess anticoagulant effects. INR stands for International Normalized Ratio and essentially is the ratio of the prothrombin time measured in the patient divided by a standard prothombin time value, and multiplied by a constant. An INR value of I means normal prothrombin times of approximately 12 seconds; normal blood clotting would be present. INR values greater thar I indicate that there is an anticoagulant effect. The higher the INR value, the greater the anticoagulant effect. Many patients taking anticoagulants have INR values of2, 3 and even up through
6.

. Immune globulins

. Immunosuppressants
. Keratinoc),te growth factor

. Interferons

192
Coplrighi O
201 I -20 12 - Denral Decks

Grunisetron (Klttil) rnd ondansetron (Zofran) *e selective 5-IIT3 receptor antagonists used to treat what condition?

. Breast cancer

. Osteoporosis . Emesis caused by cancer chemotherapy . Mucositis

caused by radiation therapy

193

Coprighr O 20ll-2012 - Dental Deck!

a variety ofconditions including: hairy cell leukemia (intederon alpha-2a) chronic hepatitis B (interferon alpha-2b), recurring genital warts (interferon alpha-n3) and treatment of multiple s clerosis (interferon beta- I a) .

Interferons are used for

Immune globulins provide passive immunity by increasing antibody titers.

Immunosuppressants are drugs such as cyclosporin which prevent organ transplant rejection.

Growth factors such

genesis.

as

keratinocle growth factor promote cell proliferation and angio-

The 5-HT3 receptor is a serotonin receptor which when activated during chemotherapy for cancer, causes emesis (nausea and vomiting). Both granisetron and ondansetron are indicated for prophylaxis of chemotherapy-related emesis, prophylaxis of nausea and vomiting associated with radiation therapy, and prophylaxis and treatment ofpostopera-

tive nausea and vomiting (PONV).

Other srotonin 5-HT3 receptor antagonists include: dolasetron (Anzemet) and

palonosetron @/oxr)

\ote:

5-HT3 stands for 5-hydroxytryptamine type 3 receptor.

. Irnmune modulators

. Monoclonal antibodies
. Immunosuppressants

. Interferons
. Colony stimulating factors

151
Copyright O
201 I

,2012 - Denlal Decks

The following drugs belong to what pharmrceuticsl class of agents:

. Adrlimumab

. Alefacept

. Inflixim|b . Trastuzumab

. Immune modulators
. Monoclonal antibodies

. Immunosuppressants
. Interferons

. Colony stimulating factors

t95
CoplriSh O 201l-2012
- Dental Decks

Pimecrolimus (Elidel) is an immunosuppressant agent used for treatment of mild to

moderale atopic dermatitis.

Sirolimus (Rapamune) is an immunosuppressant agent used for prophylaxis of organ rejection in patients receiving renal transplants.
Tacrolimus (Protopic) is an immunosuppressant agent used to treat moderate to severe
atopic dermatitis in patients not responsive to conventional therapy.

Adalimumab (Humira) rs arecombinant monoclonal antibody that binds to human tumor necrosis factor alpha (TNF-alpha) receptor sites. It is used to treat active rheumatoid
anhritis.

Afefacept (Amevive) is a monoclonal antibody used to treat moderate to severe plaque

psoriasis.

Infliximab (Remicade) is a monoclonal antibody used to treat ankylosing spondylitis,

Crohn's disease, and rheumatoid arthritis. Like adalimumab, infliximab works by binding to TNF-alpha receptor sites.

Trastuzumab (Herceptin) is a monoclonal antibody which binds to the extracellular domain of the human epidermal growth factor receptor 2 protein (HER-2) ' It is used for the treatment of patients with metastatic breast cancer whos tumors overexpress the
HER-2 protein and who have not received chemotherapy for their metastatic disease.

.Improve walefi ness during daytime sleepiness

. Improve salivary flow in dry mouth disorders

. Manage psychotic disorder

. Treat mental depression

196 Coplrighi O 201l-2012 - Dental Decks

Which herbal supplement below is known to be somewhrt ffective in treating rnild forms ofmental depression?

. Ginkgo biloba .
St Johls Wort

. Garlic
. Echinacea

. Ginseng

t97
Coplriglr () 2011,2012, DmialDecks

Modafinil (Provigil) represents a class of central nervous system stimulants used to

improve wakefuhess in patients with excessive daytime sleepiness associated with narcolepsy and shift work sleep disorder. It also has an unlabeled use to treat attention defi cit/hyperactivity disofier (ADHD). The exact mechanism of modafinil is unclear; however part of its action may be do to
decreased GABA-mediated neurotransmission.

Some studies have shown the St Johns Wort can inhibit the re-uptake of serotonin at neurcnal synapses resulting in the elevation of serctonin within the CNS. This effect is similar to those antidepressants u'ithin the flnoxetine (Plozac) fatrily. Of all the herbal supplements available to the consumer, St Johns Wort is associated with use as a mild antidepressant.

Ginkgo biloba is

herbal supplement used as a peripheral anery vasodilator

Garlic is a herbal supplement used to lower cholesterol and to inhibit platelet aggregation resulting in a decrease in blood clotting.
Echinacea is a herbal supplement and immune stimulator used to minimize the severity ofthe common cold and seasonal flu. Ginseng is a herbal supplement used to stimulate the immune system.

Chamomile has a long history of use in Europe for digestive ailments. The active constiuents of
chamomile have anti-inflammatory properties, and ease spasm and discomfort in the digcstive tract. \ote: Chamomile contains coumarin, a natumlly-occurring compound with anticoagulant or bloodrhinning effects. It should not be combined with warfarin or other anticogulants-

S.li palmetto
sia (BPH).

has long been used

in Europe to treat an enlarged prcstate or benign prostatic hyperpla-

. Increase the effectiveness ofmedications

. Decrease the effectiveness ofmedications

. Increase the toxicity ofmedications

198

copyriSlrO

201 |

-2012 - Dental Decks

AII ofthe following drugs are serotonin 5-HT1a receptor agonists usd to trert migraines EXCEPT one.Whrch ow is the EXCEPTION?

. Sumalliptan (Imitre, . Frcyatiptan (Froya)

. Naratriptan (Amerge) . Donepezil (Aricept)

. Kzatiptan (Mamlt)

Aknolnplan (Axert)

. Zolmrtrrptan (Zomig)
199 Coplrighr O 20ll-2012 - Dental Decks

St Johns Wort may induce the cytochrome P450 enzyme system to result in a more rapid metabolism ofmany drugs in rhis pathway. More rapid metabolism of a drug equates to less active drug available and less fdec/edre4 effectiveness. Specifically, data indicates probable intcractions betwen St Johns Wort and iis effect in decreasing the actions ofihe following drugs: . The HIV-l protease inhibitor indinavir . The antirejection medication cyclosponn . The sedative midazolam . The antihypertensive nifedipine

Drug-drug interactions can involve prescription or nonprcscription fo),er-the-counter)

drrJgs. Dnrgs interact by acting at lhe same receptor or signal transduction paihway, or more commonly, a drug may af]'ect the pharmacokinetics ofanother dnrg. The most common form ofdrug-drug inleraction is one drug affecting the metabolism ofanother drug, involving eifier induction or inhibition ofmetabolizing enzymes. . I nd uction of metabolism : is a reaction to certain drugs in *,hich the number of liver enzymes increases, resulting in a reduction in the flic! ofthe other drug. . Inhibition ol metabolism: is a process by which one drug either competes for metabolism ofanolher or

directly inhibits drug-metabolizing enzymes.

-\otee: *ith

''

g.rlic, ginseng, and ginkgo /gir,(go 6i1o6., are thought to interact anticoagulant or antiplatelet thrapy. Remember: Chamomile contains coumarin and should not be used in patients taking warfarin for fear ofan additivc affect. 2. St. John's wort is the herbal product most often reported !o be involved in drug-herb interac-

l.

Herbal medicines such as

l. Echinaca has potential interactions with immunosuppressants. 4. Many herbal weight loss and "herbal speed" products rely on the pharmacodynamic interaction and pseubetween ephedra and caffeine. Two primary alkaloids containcd in ephedra -ephedrine rdditive cardiovascular effects when taken with caf]eine. At higher doses, doepbedrine -have the ephedra-caffcine interaction has been cited as a cause ofdcath.
Important:The rate ofdrug metabolism can vary greatly. depending on the cytochrome p450 isozyme profile the next few years, genetic screening ofthc c)'tochrome p450 system will be able to idenriry $hich patients are likely to develop toxicity or drug-drug interactions, and with which drugs. Ultimately, metabolic screening based on studies using highly-specific probcs could bclp decide whether or not a drug is

ola patient. Over

prescribed.

***

Donepeztl (Aricep, is

cholinesterase inhibitor used in the treatment ofAlzheimer's

disease.

Migraine medications: . The most commonly used migraine medications are the serotonint f5-11fl receptor agonists, commonly known as the "triptans." All 5-HTl receptor agonrsts (triptans) have a similar chemical structure and a comparable mechanism of action. 5-HTl s and
5-HTtD receptors located on the extracerebral, intracranial blood vessels that become di)ated during a migraine attack and on nerve terminals in the trigeminal system. Therapeutic activity is caused by activation ofthese receptors, which results in cranial ves-

sel constriction, inhibition of neuropeptide release, and reduced transmission in

trigeminal pain pathways. . Ergotamine derivatives demonstrate partial agonist and/or antagonist activity against dopamine. tryptaminergic, and alpha-adrenergic receptors, depending on their site. Ergotamine derivatives have three primary actions. They (1) depress central vasomotor centel (2) constrict peripheral and cranial blood vessels, and (3) reduce extracranial blood florv and decrease hyperfusion ofthe basilar artery area. Examples include: erotamine tartrate (C aferyo t) and dihydroergotamrne (D H E - 4 5)

Combination drugs: Midrin is a combination capsule that contains 65 mg of isometheptene mucale (an ergotamine derivative), 325 mg of acetaminophen, which exerts an analgesic effect, and 100 mg ofdichloralphenazone, a mild sedative that acts centrally to allay an"riety. Note: Caffeine, which is added to many migraine combinations. helps to promote constrictive properties, and enhances absorption.

Note: Methylsergide (Sansert) blocks 5-HT2 receptors for prophylaxis against migraines.

fs

erotonin antagotrist) and is used

. Levothyroxine sodirtm (Synthroid)

. Liotbyr onine (Cytome l) . Liotrrx (Thyrolar)

. Methimazole

(Tapazo le)

200 Cop)r'ghr O
201

1,2012 - Dental Decks

Nlcotine is rapidly absorbed across the pulrnonary caplllary membrane and is delivered to the brain in high concentration within seconds of inhalstion.
The nasal spray bas the fastest delivery of the NRTs and more closely resembles
the onst

ofthe nicotine effects ofsmoking.

. The first statement

is true; the second statement is false

. The first statement is false; the second statement is true

Both statements are true

. Both statements are false

201
Cop).righr O

201l-2012

Dntal Decks

Thyroid medications: . Thyroid supplements: used to treat hypothyroidism . Levothyroxine sodi|dm (synthetic T4) . Liothyronine (synthetic Tj) ' Liotrix (T4;73= 4 l)
Note: These drugs are usually taken orally in a single daily dose. preferably before breakfast- The treatment of choice for hypothyroidism is T4. lt has a relatively slow onset of action, and its effects are cumulative over several weeks. T3 has a more rapid onset ofaction and dissipation ofaction. Adverse side effects include nervousness, nausea, dianhea, tachycardia, tremoq weight loss and heat intolerance.

. Thyroid suppressants: used to treat hyperthl,roidism . Methimazole (Tapazole) . Propylthiouracil (PIUI

\ote:

These drugs inhibit thyroid peroxidase, which is an enzyme expressed mainly in the thyroid that liberates iodine for addition onto tyrosine residues on thyroglobthyroxine (I4.; or triiodothyroulin for the production of the thyroid hormones nrne (Tj). Through reduced absorption of iodine, thyroid hormone synthesis is diminished. Adverse effects include rash, nausea, and agranulocytosis.

\ote: Thyrogen is a recombinant DNA

source ofhuman TSH useful in the management

and lreatment of thvroid cancer oatients.

\fan) phannacologic approachcs havc bccn uscd to hclp pcoplc stop smoking. h current usc arc thc nicotinc rcplaccnlcnt thcrapy l\'Rl products, bupropion r'4'han ll/elbutriD zt\d \arcnicline (Cha tn).
\icotine rcplaccmcnt producls are meant to help palients stop smoking. They arc not mcant to belp gct
rhrough a long flight or an all-day mccting in a nonsmoking building.
a paticnt

Class

Generic Name

Tr.de Name
Nicorette

Formulation
Gum

Nicorine replacement lherapy Nicotine polacrilex Nicotine

Nicodem CQ
Habitrol

Transdemal Transdemal
Transdermal Transdermal Nasal spray

Nicohol
ProStep

Nicotrol NS

Nicotrol inhaler
Co1nmit Anridepressant
N

Oral inhaler Tablet Tablct

Bupropion Varenicline

Zyban, Wellbutrin

icotine rcceptor agonist

Chanlix
used tvpe

\ote_q

).'lhcp^tch (trunsdamdl) is thc most commonly 2l mg strcngths for trcatmcnt inilialion.

ofNRT' Patchcs arc availablc in l5 and

2. Thc gum dclivcrs nicotinc faster than thc patch and can be uscd for incidcncc ofcraving. Thc gum is availablc in two strcngths: 2 mg and 4 mg. 3. Thc lozenge also comcs in 2 mg and 4 mg doscs and dclivcrs about 25% morc nicotinc than gum. .1. Thc nasal spray has thc fastest delivery ofnicotinc ofthc NRTs. 5. Inhaled nicotine (xslng the nirctine ifihaler) is absorbcd in lhc mouth not in the lungs. Each cartridgc contains l0 mg nicotinc and dclivers 4 mg. It also contains I ng mcnthol. 6. Bupropion as a systcmic medication sccms to rcducc thc craving forcigarcttes orlhc urgc !o smokc. Its mcchanism ofaction is unclcar 7. !arenicline is thc ncwcst dmg in thc smoking ccssation arscnai. Note: Thc FDA has issucd an alcrt

to providcrs to monitor patients taking this medication for dcpressior, scvcrc mood swings, abnormal drcam statcs. and thoughls ofsuicidc.

. Analgesics

. Anti-inflammatories
. Antitussives . Antidiarrheals

. Preanesthetic medications

202
Coplright e 20ll-2012 - Denlal Decks

. Codeine

. Oxycodone
. Hydrocodone . Meperidine

. Morphine
. Fentanyl

203
CopFighr O 201l-2012 - Dental Decks

Opiates are very effective analgesics, They suppress the cotgh reflex (tntitussive). They cause constipation and thus are effective antidiarrheal agents. When used as preanesthetic medications, opiates permit a reduction in the amount of general anesthetic required for surgical anesthesia.
Some common side effects ofopiates (narcotics) include: sedation/drowsiness, dizziness and nausea. Other less common adverse effects are vomiting, h)?otension, irregular/labored breathing /dyspnea), lightheadedness, nightmares and insomnia.

i\oq: '.td;a

- - ... l. Respiratory dpression

is dose related and is the cause of death in narcotic drug overdose. It can happen with any of the narcotics. 2. Abuse can and does occur with all the narcotics. They are all controlled
drugs falling under DEA Schedule

II or DEA Schedule III ofthe

schedules

of

controlled substances. 3. A DEA number is required in order to prescribe narcotics.

Opioid analgesics are thought to inhibit paintul stimuli in the substantia gelatinosa ofthe spinal cord, bminstcm. rcticular activating system, thalamus, and limbic system. Opiate rcccptors in each of thcse areas interact with neurotransmittcn ofthe autonomic nervous system, producing alteralions in reaction to painful stimuli. fhc opioid action ofthc drug manil-e\1. as: . Decreased peristaltic motility . Nausea and vomiting . Dro\\'siness . Respiratory depression . Euphoria . Depression ofthe cough reflcx . \fentalcloudrng . \lrosts constriction) . Orthostatic hypotension
@upillan,
a narurally occurring opiate tha! is metaboliTed chiefly through glucuronidation by uridine ciphLriphare glucuronosyl transferase fUG4 nzymes in the liver These enzymes produce an active analgesic meiaboltle ( m o rp h i n e- 6 - E: lucuron id e).

\Iorphine is

Srgri and s]mptoms ofacute opioid intoxication:!he intoxicaled person is stuporous or asleep and has cons-icied pupils /pir-poi t p?./plls/ and depressed respimtion- As the severity ofintoxication increases, coma ensucs. \ote: Death from acute intoxication by an opioid analgesic is the result ofpmfound, direct respiratory
depression.

Remember:

L Codeine is weaker f/e.rr polr, than morphine and less addictiv. 11 is converted to morphine by cyrochrome p,l50 2D6. Note: It diffcrs from morphine in that a methoxy (-OXIIj) substitution replaces the hi dro\yl (-OH) group on the aromatic ring ofthe molecule. This relatively minor structural change pro\ldes codeine with significant oral effectiveness.
has a similar potency as morphine. ln combination with acetaminophen it is known as Prcocet or Tylox. 3. HJ''drocodone has a similar potency as morphine. In combination with acetaminophen it is known as

:. ox]codone

vicodin and Lorcet. 4. Meperidline (Denero, is more potent than codeine but less potent than morphine butjust as addictive. It has a shorter duration ofaction. It is the only narcotic agent tbat does not cause miosis lPupillary con5. Methadone (Doloprl,e) is an opioid agonist used in maintenance for treating opioid addiction. 6. Buprenorphine fsrrrle, is an opioid partial agonist uscd to treat opioid dependence.

Which sdverse effect is associated with opioid anNlgesics and not non-narcotic pain relievers?

. Allergic response

. Nausea . Vomiting . Respiratory depression

20t
Coplright C

20ll

2012 - DenlalDcks

PIIARMACOLOGY

All ofthe folfowing are opium alkaloids, EXCEPT oae.

Which one is the,EXCZ'PZ1O1V?

. Meperidine

. Morphine
. Codeine

205
Cop),right O

20ll

2012, DenialDecks

The most significant and well-known adverse reaction to opioids is respiratory deprssion. Death secondary to opioid overdose is nearly always due to respiratory depression. When opioids are appropriately used, the risk of severe respiratory depression is generally small as tolerance rapidly develops to this effect.

Drug
Morphine

Length ol Effcctivcness

Other Information
Starts to work quickly. Oral form can bc vcry effective for cancer pain.

lV or lM: 2-3 hours

By rnouth: 3-4 hours
Sustaincd relcase: 8-12 hours

Codeine

By mouth: 3-4 hours Taken \lith aspirin or acetaminophen

Less potent than morphine

Meperidine
Methadone Propoxyphene

IV or IM: about

3 hours

Can cause seizurcs, tremors, and muscle spasms

By mouth: not very effective Bv mouth:4-h hours. somelimes longcr By mouth: 3-4 hours Also used for treatins heroin withdmwal Gererally taken treat mild pain morphine Usuallv combined wirh acetaminophen Usually combined with aspirin or acetaminophen
Can block painkilling action of other opioids. Aboul as strong a codeine. Can cause confirston and arlxiety. especially in the elderly.

\ri!h aspidn or acetaminophen to

Can be used instead

Le\'olphano!
Hr"drocodone Oxr codone Pentazocine

lV or IM: 4 hours tsy mouih: 4 hours

By moulh: 4-6 hours Bv mouth: 3-4 hours By mouthr up to 4 hours

oral form is strong.

of

Chernical classihcation of opioid analgesics:

Opium alkaloids: . Morphine . Codeine

Sl nthetic deriYatives:

. )Iorphine group:
. Hydromorphone (Dilaudid) . Oxymorphone (l'l umorphan) . Nalbuphine /?fuDaif . Codeine group: . Hydrocodone (in Vicodin) . Oxycodone (in Percodan, Percocet and Tylox)

Synthetic narcotics: . Meperidine group: . Meperidine (Demerol)

. Alphaprodine (Nisentil) . Alfentanil (Alfenta) . Fentanyl (Sublimaze) . Sufentanil (&r&rta) . Diphenoxylate (in Lomotil) . Loperamide (in Imodium)

. Methadone group: . Methadone (Dolophine) . Propoxyphene (Darvott)

. Morphine
. Naloxone . Propranolol

. Ibuprofen

206
Cop).righr O 201 I ,2012 - Dental Decks

. Beta-endorphins . Morphine

. Enkephalins
. Dynorphins

207 Coptrigln
@

20i 1,2012 - Dntal Decks

Naloxone (Narcaz) is a narcotic antagonist and is used in medical emergencies to teverse narcotic overdose. Overdose of narcotics results in respiratory depression and death due to respiratory shut down. Naloxone will reverse the respiratory depressant effects ofthe narcotics thus counteracting the lethal effects of these agents. Naloxone is given intravenously, intramuscularly or subcutaneously. Note: Naloxone does not have agonist activity at any opioid receptors.

Nalmefene (Revex) and naltrexone (ReWa) are the other two narcotic reversal agents
used to reverse the respiratory depressive effects

olthe narcotic analgesics.

Typical narcotic analgesic drugs which are reversed by naloxone (Narcan), nalmefene
(Revex), and naltrexone (Rena) Lnclude:

. Codeine
. Morphine

. Hydrocodone

'

Oxycodone

. \{eperidine (Demextl) . Fentanyl

\ote: Naltrexone (Rel/ia) is also

used to treat alcohol dependence.

opiate receptors in the CNS mediate analgesic activity. Opioid agonists occupy the same receptors as en_ dogcnous opioid peptides, and both alterthe central release ofueurotransmitters ilom afferentrerves sensitive to no\ious stimuli. They decrease presyraptic release ofneurotranmitters and incrcasc postslnaptic potential. The opioid reccplors all have a common general strucfur. They are characleristically G protein-linked receptors enrbedded in thc plasma nrembrane ofneurons. Once the receptors are bound, a portion ofthe G prorein /Gtl is activated, allowing i! !o diffxse within the plasmn menbmne. The G protein moves within the an cnzyme or an ion channel. membrane until it rcaches ils larget Opi[)id receplors in lhe centml nervous system are thought to be activated by endogenous chemicals under Fh\ iiologic condirions. fie body coniains three types ofthese chemicals that produce morphine-like effects

-cithcr

. Beta+ndorpbins bind to opioid receptors in the brain and have potent analgesic activity. . Enkephalins bind to opioid reccptors in the brain and are more widely distributed in the brain

than lhc

bera-endorphins. Seem !o play a role in pain perception, movement. mood, and behavior . Dlnorphins are the most powerful ofthese cbemicals and are lbund throughout the central and peripheml nen ous syslems. Some research supports the theory that they regulate pain at the spinal cord level, influence feeding behavior at the hlpothalamic levcl and function with other cndogenous opioids to regulatc
the cardiovascular systcm.

Opioid receptors:

l. mu mediate morphinelik supraspinal analgesia, mitosis, respiratory depression, uphoria, physical dependence, and supression ofopiale withdrawal. Nolei The protot)?ical opioid agonist for this receptor is morphine, and its analgesic activity is considered to depend on its binding to this reccptor 2. della mediate antagonist activity. Note: The nkephalins are considered to be the q?ical agonist tbr this recptot L kappa (K) mediate spinal analgesia, respiratory depression, and sedation. \ote: The dynorphins are

(!)

(6)

thought to be the R?ical agonist for this receptor Sites of analgesic action of opioids: The opioid drugs produce analgcsia by actions at several levels ofthe ncwous system, in particular, inhibition ofneurotransmitter rcleasc f.om the primrry alferent terminals in the spinal cord and activrtion ofdescending inhibitory controls in the midbrain.

*** Opioid analgesics (i.e., motphine. codeine, mepericline. propoxvp,ftcn, eL..) mimic endogenous opioids at CNS opiate recepiors, raising the pain threshold and increasing pain tolerance.

. Morphine . Hydrocodone (component of Wcodin) . Oxycodone (component of Percocet) . Meperidine (Demerol) . Codeine . Fentanyl

204 Coplriglit C
201 I -20 l2 - Dmral Decls

. Acetaminophen . Ibuprofen (Motrin; Advil)

. Hydrocodone with acetaminophen

. Aspirin

209 Cop)right
@ 201

l'2012 - Denral Decks

Therapeutic indication for opioids (narcotic analgesics) are the relief of moderate-tosevere pain, as preanesthetic medications, as analgesic adjuncts during anesthesia, as antitussives, and as antidiarrheals. Note: They are administered with caution to patients with head injury or those with a history ofdrug abuse and dependency.

l. Morphine is not used in dentistry because ofits high addictive liability. 2. Hydrocodone in combination with acetaminophen is known as Vicodin,
Lorcet, Lortab, Maxidone, and Zydone. 3. Ilydrocodone in combination with ibuprofen is known
as

Vicoprofen,

4. Oxycodone in combination with acetaminophen is known as Roxicet Percocet, and lllox. 5. Oxycodone in combination with ibuprofen is known as Combunox. 6. Oxycodone alone is klown as Oxycontin. It is more potent than codeine.

7. Meperidine (Demerol) in combination with promethazine is known as

Mepergan Fortis.
8. Codeine in combination with acetaminophen is known as Tllenol #3. 9. Fentanyl is available as a transmucosal preparation known as Actiq, a trarsdermal patch formulation known as Duragesic and as an intravenous prepa-

ration known as Sublimaze, Among the opiates available for use in dentistry, hydrocodone products are commonly
the drues ofchoice.

Ibuprofen and other non-selective NSAIDs (inhibitors of both cyclo-oxygenase I and q clo-orygenase 2 enzymes) snch as naproxen (Anaprox) and flurbiprofen (Ansaid) inhibit platelet aggregation. This action would enhance the anti-coagulant effect of warfain (Coumodin) to increase the risk ofbleeding. Aspirin inhibits platelet aggregation to potentiate the anticoagulant effects of warfarin (Coumadin) and increase the risk ofbleedlng.

Acetaminophen is a non-narcotic analgesic that dos not affect platelet aggregation nor does it affect the coagulation pathway. Thus, it will not affect the anticoagulant nature of warfartn (Coumadin). Acetaminophen can be given safely to patients taking warfarin

lCoumadi

Hyrocodone with acetaminophen is a combination ofa narcotic analgesic with acetaminophen. Common brand names for this combination are Vicodin, Lorcet and Lortab. Hydrocodone and the entire drug class ofnarcotic analgesics do not affect blood clotting and will not enlance the anticoagulant effects of warfarin (Coumadin). Narcotics with acetaminophen can be given safely to patients taking warfarin (Coumadin).

. Nausea . Peptic ulcers

. Insomnia
. Constipation

210
Cop'.righl O
201 I

,2012 - Dntal Decks

Which drug is r synthetic opioid analgesic used as an inkrvenous sedative and is more potent than morpbine?

. Meperidine (Demerol)

. Pentazocine (Talwin) . Propoxyphene (Danon)

. Fentanyl

211 Copldght O
201

l'2012 - Dental Dcks

The most common side effect of the narcotic (opiqte) analgesics is nausea. The most serious side effect of the narcotic analgesics is respiratory depression. The cause of death from overdose ofnarcotics is respiratory depression and shut down ofthe respirarory sysrem. Narcotic analgesics do not cause peptic ulcers. Nor do they cause insomnia, but rather would cause drowsiness and sedation since narcotics depress the conscious centers of
the brain.

Fentan!-l (Sublimaze)is a potent narcotic analgesic used primarily as an intravenous supplement during conscious sedation procedures or proccdures requiring general anesthesia. Fcntanyl is 80100 times more potent than morphine. Fentanyl is also avaifable as a lollipop-type lozenge (brand name Actiq) for transmucosal absorption and as a transdcnnal patch (brand name Duragesic) for dclivcry thrcugh a patch applied to the skin. Note: Fcntanyl congeners include Alfentanil, Sufentanil, and Remifentanil.

Meperidine (Denerol) is used as an intravenous supplement during conscious scdation procedures. However, it is less potent than morphine and much less potent than fentanyl. Meperidine
(Demerol) is also wed as an oral medication for pain control aftcr dental surgery. Note: A mctabo-

lite, normeperidine, is a CNS stimulant. lmportant; Contfaindicated with MAO inhibilors

(e.g.,

phen;lzine ard tru llcypromine)

Pentazocine (Talwin) is chemically related to morphine and has weak analgesic properties. 1t is mixed agonist-antagonist drug, having agonist activity at some reccptom and antagonist activity at other rcceptors. It is not used intravenously to produce conscious sedation. Pentazocine has abuse liability. Note: Talwin Nx tablets contain naloxone which is added to deter misuse.
a

Propoxyphene fDanon) in the form ofpropoxyphene napsylate with acetaminophen is known as Darvocet-N 100 and is useful tb. pain control after dental surgery. It is taken orally and not used inlravenously. Darvocct-N 100 has low abuse liability. l\-ote: lt is less potent than codeine and a metabolite, norpropoxyphene, is a CNS stimulant. Tramadol (Ultran) is an opioid partial agonist. It is not a scheduled drug. Use great caution in combination with MAOIs (e.g., phenylzine and tranylcypromine).

. Codeine
. Morphine
. Hydrocodone

. Meperidine (Demerol) . Oxycodone . Voltaren

212
Cop',righr O

20ll

2012 - DntalDecks

AII of the followitrg sites are generally accepted for IM injections EXCEPT one. Which one is the EXCEPTIOM

. The buttocks

. The biceps muscle . The deltoid muscle

. The anterior thigh

213
Coplright O
201 I

-2012 - Dental

Deks

***

Voltaren is a NSAID which do not produce drug dependence and addiction.

The other analgesics belong to the opiate class of drugs. They are also klown as narcotic analgesics since the actions ofthis family is to cause drowsiness and sleep as a side effect.
The opiates produce drug dependence leading to addiction. Psychic dependence, physical dependence, and tolerance can develop upon repealed administration. Psychic dependence is unlikely if an opiate is taken for a short period for pain relief. Physical dependence is a condition in which continued administration of the drug is required to prevent unpleasant withdrawal symptoms. Tolerance occurs when increasingly large doses ofopiate are required in order to produce the same degree ofanalgesia. Opiate drugs used in dentistry to provide pain reliefafter dental surgery include:

. Codeine . Hy drocodone O)icodin) . Oxycodone (Percocet rylox) . Meperidine (Demerol)

***

For young children, the anterior thigh is usually the place to give IM injections.
a

Absorption from an intrarnuscular injection is often faster and there is abilit]' than with oral administration.

higher bioavail-

Proper depth of needle in muscle: In big muscle (adult) go in one inch; in children go in one-quarter of an inch. Never go beyond two-thirds ofthe needle length.

. Pharmacologic agonist

. Pharmacologic antagonist

211 Copright C
201

l-2012 - Dental Decks

. Topical administration . Oral ingestion

Subcutaneous inj ection

. Intravenous injection

215
Coptrighr O 201|,2012 - Dntal Decks

Drugs that bind to physiologic receptors and mimic the regulatory effects ofendogenous signaling compounds will produce a pharmacologic effect as a result of binding to the receptor. A drug that elicits a full response through this process is referred to as a phar-

macologic agonist.

A partial agonist is a drug which acts on the physiologic receptor but elicits an effect which is only partly as effective as an agonist drug.
a drug which binds to the physiologic receptor but does not trigger an When artagonist is present, the agonist drug cannot reach the receptor site to proeffect. duce an effect.

An antagonist is

1. Competitiv antagonism occurs when a response can be achieved by increasing the dose of agonist in the presence ofantagonist. 2. Noncompetitive antagonism occurs when a response cannot be achieved with increasing doses of agonist in the presence ofantagonist.

Common routes of administration ofdrugs:

1.

Parenteral administration (not by wa!" ofintestine or GI tract) . Intravenous (lV) - diectly into the bloodstream. Acts very rapidly. . Intramuscular |1M/ injected into a muscle area, where it is promptly absorbed

. Subcutaneous

injection beneath the skin. Absorption may be less rapid.

2. Enteraf administration @y v,q) ofthe intestine or GI tract)

. Buccal or sublingual

a tablet is placed under the tongue or in the cheek (most common route), the drrrg is swallowed. It is the most convenient for safe drug administration. It is safe, painless and economical. . Rectal - the drug in solution (enema) or suppository form is inserted into the rec-

. Or^ltum

3. Inhalation 4. Topical

the drug is given as an aerosol into the respiratory tract. the drug is placed on the skin for a local effect.

administration

5. Transdermal - the drug is placed within a "patch" and placed on the skin to be absorbed into the systemic circulation.

. Lungs . Liver
. Brain . Kidneys

. Gastrointestinal tract

216
CoplriSht O 201 l-2012 - Dertal Decks

. Does; extrinsic . Does not; extrinsic . Does; intrinsic . Does not; intrinsic

217 copyiShr o
201 I ,2012 - Dental Decks

Hepatic metabolism of drugs occurs in Phase I reactions catalyzed by a microsomal mixed-function oxidase system (a/so known es the P-450 system) and in Phase II reactions known as conjugation reactions.
Phase

I reactions: . Occur in the liver microsomal enzyme system (mixed-lilnction oxidase system or P450 system).In this system, drug metabolism occurs in three basic pattems. First, the active parent drug can be converted to the inactive metabolite. Second, an active parent drug may be converted to a second active compound which is subsequently con-

verted to an inactive compound; and

transfonned to an active compound.

thirdly an inactive

parent drug may be

. The most common raction in drug metabolism is an oxidation reaction in which oxygen in the form ofhydroxyl group is attached to the drug molecule. . There are at least eight distinct groups of microsomal drug metabolizing enzymes: These enzymes "families" are identified as a cytochrome (CYP preJix) followed by their numerical digestion (e.g., lA2).Thusrhe enzyme CYP lA2 is a distinct drug metabolizing enzyme that converts a variety of drugs to the oxidized product.
Phas

II

reactions:

. Conjugation

reactions involve coupling the drug with an acid present in cells (rrsaalh glucuronic acid). \,,lhen coupled to glucuronic acid, the process is known as glucuronide conjugation with the resulting metabolite refened to as the "glucuronide." . Conjugations occur in the liver, kidney and to a lesser extent in other tissues. . Conjugation ofdrugs results in polar, water-soluble compounds that are rapidly excreted in urine. Thus, the parent drug is effectively rendered inactive and transportd out ofthe body by this process.

There are four major families ofphysiological receptors that drugs can bind to produce effects:

. Receptors

as enzymes 6.e., cell surface protein kinases): These kinases exert their regulatory effects by phosphorylating proteins within the cell which alters the cellular biochemical activities. By binding to these kinases, drugs can also cause the alteration in biochemical activities resulting in a drug effect.

. Ion channels: Drugs can bind to ion channels in cell membranes to cause opening or
closing. This alters the cell's membrane potential to result in
a

drug effect.

. G protein-coupled receptors: When drug binds to these receptors,

in a drug effect.

second messengers are produced such as cyclic AMP to produce an effect within the cell. This results

Receptors for steroid hormones are soluble DNA-transcription factors within the nucleus that regulate the transcription of specific genes. Modification ofthe transcriptions ofthese genes results in a drug effect.

. Receptors in cll nucleus:

. Oral

.IV
. Rectal

. Inhalation

218
Coplrishr O
201 I

'2012 - Dental Decks

. Actlve transport . Facilitated diffusion

. Filtration . Simple diffirsion

Copltisht

@ 201

219 l'2012 - Dental Decks

Howeveq it is also the most unpredictable and least effective route available. Drugs taken by mouth have to be absorbed (as ually fr om the small intestine) before they can be transported to their site ofaction. Absorption may be slow, unpredictable and inegular due to the presence of variable amounts of food in different stages of digestion and to the varying degrees ofacidity and alkalinity ofthe digestive juices. Moreover, blood from the intestinal tract passes first to the livr: some drugs are metabolized in the liver and others may be stored there to be released only slowly. These considerations make it clear that oral administration is usually unsuitable in emergencies or on other occasions when a rapid effect is needed.

Note: After oral administration, drugs will generally be absorbed best from the duodenum. The duodenum has a large surface area due to the presence of villi and n.ricrovilli.
Note: A major advantage of IV administration ofa drug is it allows for titration ofthe
drug. Other advantages of IV administration include: . Rapid onset . Drugs that cause irritation when administered subcutaneously can be given IV with

no irritation

. In case of emergency,
injected

there is an open line through which emergency drugs can be

One major disadvantage of IV injection is that since it has such a rapid onset ofaction, overdosage may have effects so immediate that it is impossible to reverse them.

The mechanism of drug transfer across biological membranes is by: L Passive transfer essential to various processes of metaboltsm

-is . Simple diffusion: Iipid-soluble substances move across the lipoprotein membrane by.' this process. The majority of drugs penetrate biomembranes by this process through membrane phospholipids. The amount of drug dissolving in the membrane at any time is directly proportional to the concentration gradient and its degree of lipid solubility (Note: Only nonionized drugs are soluble in lipid). . Filtration: water-soluble molecules small enough to pass through membrane channels may be carried through the pores by the bulk flow of water. Drugs ofmolecular u eights of 60,000 or less can "filter" through capillary membranes.
. Active transport: lipid-insoluble substances (for example gluco.re) are shuttled across plasma membranes by forming complexes with specific membrane constituents called carriers. These carrier molecules within a cell fumish energy for ransportation ofthe drug to regions ofhigher concentration. Facilitated diffusion is the term given to carrier-based transfer when the driving force is simply the concentration difference ofthe drug across the membrane.

3. Specialized transport

Note: Osmosis is the movement of a pure solvent, as water, througl't a semipermeable

membrane from a solution that has a lower solute concentration to one that has a higher concentration. The membrane is impermeable to the solute but is permeable to the solvent.

Remember: The physiochemical properties ofdrugs that influence their passage across biologic membranes are: lipid solubility, degree of ionization, and molecular size and
shaoe.

. 5 milliliters

. l0 milliliters
. l5 milliliters
. 20 milliliters

220 Copfight C 20ll-2012, Dmial Decks

. Levodopa (Larodopa, Dopar)

. Prazosin (Minipress)

. Indomethacin (Indocin) . Morphine

221
Cop,'right C 201l-2012 - Dental Dsks

lndomethacin (ndoclry' is an NSAID which may cause GI bleeding, ulcers and possible stomach perforation. Drugs that may produce orthostatic hypotension:
. -{ntih} pertensiyes: for example prazosm (Minipress)

***

. Phenothiazines: for exanple chlorpromazine and thiondazine (Mellaril) . Triclclic antidepressants: for example doxepin (Sinequan), amitriptyline (E/avll)
and imipramine I Tolianil) . \arcotics: for example meperidine (Demerol) and rnorphine

. -Lntiparkinson drugs: for example levodopa (Larodopo. Dopur) and carbidopa

ler odopa /Slnenet)

Orthostatic h)'potension (also called postural hypotension) is abnormally lorv blood

pressure occuning when an individual assumes the standing posture.

Important: Following vasovagal syncope, orthostatic hypotension is the most likely

cause of transient unconsciousness in the dental office. Many factors have been identi-

fied that rnay be responsible for the development of orthostatic hypotension, including several which are important to the practice of dentistry. They include the administration
and ingestion ofdrugs, prolonged recumbency and convalescence, an inadequate postural reflex, pregnancy, various defects in the legs, Addison's disease, physical exhaustion and starvation and chronic orthostatic hypotension (Shy-Drager sludrome).The incidence increases with age.

Pain that has no organic basis and is fixed upon some portion ofthe anatomy is referred to as:

. Intractable pain
. Refened pain . Psychogenic pain . Phantom pain

222 Coplaighr C2011,2012 - Dental Decks

Schedule

. Schedule II

Schedule

III

. Schedule IV

Schedule

Copltighr O

201

l-2012 - Dental Decks

*** For example,

putated.

the sensation ofpain felt in a limb, although that limb has been am-

Other terms to know:

.Intractable pain: is pain that is resistant or refractory to ordinary analgesic agents . Referred pain: is pain felt in an area other than the site of odgin, such as pain near
the shoulder associated with biliary disease . Psychogenic pain: is pain produced or caused by psychic or mental factors rather than organic factors

Remember: Pain threshold refers to the lowest level ofpain

a patient

will

detect.

category ofdrugs not considered legitimate for medicinal use. Among the substances so classified by the DEA are mescaline, LSD, heroin, and marijuana. Special licensing procedures must be followed to use these or other Schedule I substances. Schedule I

Schedule II a category ofdrugs considered to have a strong potential for abuse or addiction. but which have legitimate medical use. Among the substances so classified by the DEA are Morphine, Cocaine, Pentobarbital, Oxycodone, Methadone, and straight Codeine. Schedule III - a category ofdrugs considered to have less potential for abuse or addiction than Schedule I or II drugs. Among the substances so classified by the DEA are var-

ious analgesic combination compounds containing codeine fi.e., acetaminophen and codeine - \'lenol #3) and various analgesic combination compounds containing hydrocodone (i.e., hydrocodone and acetaminophen

Schedule IV - a category of drugs that have less potntial for abuse or addiction than those of Schedules I to III. Among the substances so classified by the DEA are diazepam (Valiurn),lorazepam (Ativan), triazolam (Halcion), alprazolam (Xanax), and chloral hydrate.

-l'icodin;

Lorcet).

Schedule V a category of drugs that have a small potential for abuse or addiction. Among the substances so classified by the DEA are many commonly prescribed medications that contain a small amount ofCodeine.

Note: Schedule II and III must have a written prescription signed by the health professional (aws vary from stqte to state). The FDA determines which drugs are to be sold by prescription only. The prescription must have the address ofthe patient and dentist as well
as the DEA number

olthe dentist.

. High therapeutic index and is, therefore, very dangerous

. High therapeutic index and is, therefore, relatively safe

. Low therapeutic index and is, therefore, very dangerous . Low therapeutic index and is, therefore, relatively
safe

224
Cop,righr O 201l-2012 - Dental Decks

. Intramuscular . Inhalation

. Sublingual
. Oral

225
Coplright O 201 I,20 l2 , Denial Decks

Explanation: The purpose ofan acute toxicity test is to determine the nature and extent

ofthe untoward reactions which might iollow the administration ofa single dose (or an overdose) of a dntg. A quantitative aspect ofacute toxicity testing is the determination of
the drug's lethal dose using mice. This is usually expressed as the LD59. Standing alone,

it

conveys less information than does the ratio of the lethal to the effective doses (LD5/ED50), a quantity which is often known as the therapeutic index (a measure of drug safety).The greater a drug's therapeutic index, the less likly that fatalities will follow an accidental overdose.

..' --.,. 1. ED5g is the effective dose at which 50o% ofpeople will respond. .:Noted.' 2. LD56 is the lethal dose at which, in theory 50% ofpeople will die.

.;g..4

***

Lethal doses are always determined in mice, not people

oftherapeutic window is not the same as therapeutic index. The therapeutic window describes the range between the lowest therapeutic concentration and the beginning of toxicity. Some drugs have a very nanow therapeutic window, making patient monitoring especially important. 4. Toxicity results when the dose ofthe drug is excessive for the particular patient.
3. The concept

5. Side effect: an adverse effect that occurs within the therapeutic dose range ofthe drug. 6. Idiosyncratic reaction: a reaction to a medication that is unusual and unpredictable, specific to a particular person. Unlike allergy. it can occur on first exposure to the medication, unlike a side effect, it affects only very few

individuals.

The oral administration of a drug is the one most acceptable to the patient. It is convenient because drugs can be given in the form oftablets or capsules which contain an exact dose. lt is easy and the patient can take the drug without help from anyone else.
One ofthe disadvantages of drugs taken by mouth is that they have to be absorbed (trsuulh fiom the small intestine) before they can be transported to their site ofaction. Blood from the intestinal ract passes first to the liver: some drugs are metabolized in the liver ( "lirst-pass elfect") and others n.ray be stored there to be released slowly. This considera-

rion makes it clear that oral administration in usually unsuitable in emergencies or on other occasions when a rapid effect is needed.

Intramuscular injection is an injection made into a large muscle. The advantages of IM injection are that it results in uniform absorption and that it can be used for solutions too iritant for subcutaneous injection. The speed ofabsorption of drugs given by IM injection depends on dre vehicle in which they are dissolved: absorption is rapid from aqueous solutions and slow from oily solutions.

: . ...
. The movement of

The term bioavailability ofa drug rfers to:

a drug into the body tissues over time

. The dissolution of a drug in the GI tract

. The measurement of the rate and amount of therapeutically active drug that reaches the
systemic circulation

. The relationship between the physical and chemical properties ofa drug and the systemic absorption ofthe drug . The amount ofdrug destroyed by the liverprior to syslemic absorption from the GI tract

226
CoplriSht O 20ll-2012 - Dental Decks

Factors inlluencing hepatic drug metabolism include which ofthe followlng?

. Microsomal enzyme inhibition

. Microsomal enzyme induction .

Plasma protein binding

. Genetic factors
. Liver disease
. All of the above

227 CoD{iglu O 20ll-2012

D{tal

Decks

The bioavailability of a drug is allected by:

. The dissolution ofa dnrg in thc Gl tract

. The destnrction ofa drug by the liver

Phrrmrcokinetics focuscs on the proccsscs concemed with absorption, distribution, biotransfomation (metabo' lisn), and cxcr.tlon (elim r'nalior) of drugs. . Absorption: thcre are four prim.ry frctors that must be considered in evaluating drug absorption: l. Drug chxncteristics: . Formulrtion ot the drug . Co[centration of the dru$ the higher the concentration, the more quickly the drug is absorbcd . Lipophilic drug formulrtions are morc rcadily rbsorbsble: nonionized drugs are more lipid soluble and may readily difuse across cell membmns . Acidic drugs become nonionized in the acidiry ofthe stomach .nd then dilluse across mcmbranes:
basic drugs tend to ionize and arc not well absorbed in the stomach 2. Routes of edministration: the most common routcs for giving medications include oral, topical, subcutancous, infamlscular, intravenously, and rectal.

3. Blood flowi circulation at the sitc ofadministration is importrant in the drug absorption Foccss. Dc:crcased circlJl^tion (as see'n fu congestiw heart fail rc) vtill result in dccrcascd drug absorptlon.
4. Cell membrrne ous tissues in thc body

chtractedstics: dtugs cross membranes via passivc diffusion or active tmnsport

. Distribution: is thc trrnsport ofa dnrg in body fluids from thc bloodstesm (at lhe sile ofabsorptiotr) to vai. Biotranstormation a/n etabolism)t is the chemical inactivation of a drug lhrough convcrsion to a more waler-soluble compoud that can be excreted from th body. It occurs primarily in the liver. Involves two major stcps: Phas I makcs the drug morc hydrophilic through oxidation, reduclion, or hydrolysis. Phase lI is called glu' curonidrtion, it involves conjugrtion.

. Eliminrtio[: is the proccss by which drugs and their metabolites

kidney
are

are removcd from the body. The live. 8nd the major organs responsible for elimination. Most climination occurs through excrction by thc kidneys. Thc procsses involved in rnal elimiDation consist ofglomrular liltrution, tubuhr secretion' rdd par-

wo

tirl

rerbsorDtion.

Factors Influencing Hepatic Drug Metabolism: and environmental agents can inhibit many of the CYP isoforms of the P-450 microsomal drug metabolizing system. Thus many drugs which ordinarily are metabolized by the particular CYP inhibited will not be effectively metabolized and will achieve higher than expected blood levels. . Microsomal enzyme induction: agents which induce higher levels ofthe microsomal drug metabolizing enzymes may cause a more rapid metabolism ofother drugs thus resulting in lower than expected blood levels ofa drug. . Plasma protein binding: drugs highly bound to plasma proteins will not enter the liver to be metabolized, thus resulting in a longer plasma halfJife ofthe drug. . Genetic factors: there is individual variance through genetic factors which contribute to differing rates of drug metabolism in the hepatic microsomal enzyme system. . Liver disease: hepatic impairment and liver disease most often will result in impairment ofthe microsomal drug metabolizing system. This most often results in elevated levels of unmetabolized drug. Note: Mos! drugs are given at lower doses in hepati cally impaired individuals.

. Microsomal enyzne inhibition: many drugs

. Glomerular filtration . Microsomal enzyme induction . Renal tubular reabsorption . Active hansport tbrough renal tubular cells

Coplright C 201l-2012 Dental Decks

The average time for ths onset of drug effect after subcutaneous rdministration is:

. Immediate . 5 minutes

15 minutes

. 30 minutes

229 CoDright O 20ll-2012 - Detrtal Decls

. Glomerular liltration: all drugs are filtered through the glomerulus to enter the renal tubules. The amount of drug varies according to the degree of plasma protein binding,
and bound drugs are not subjected to filtration.

. Tirbular reabsorption: once they enter the renal tubules, drugs may be reabsorbed back into the blood stream through the renal tubular cells. Reabsorption favors the highly lipid soluble agents; the converse is that highly polar compounds are not effectively reabsorbed and are effectively excreted from the renal tubules.

. Active transport through renal tubular cells: the rate of renal elimination also depends on whether active transport into or out ofthe tubular fluid occurs. Other excretory pathways for drugs:
. The gastrointestinal tract excretes some drugs through the feces. This is not as prevalent as urinary excretion. . Most drugs can be detected in saliva after administration, but the salivary glands are not considered a route ofdrug excretion since the drug is re-swallowed along with the
saliva.

. Lungs excrete volatile compounds that were originally inhaled into the system. Nitrous oxide and the volatile general anesthetics are excreted by this route. . Some drugs are excreted in the sweat' but this route accounts for only a small percentage of drug excreiion.

Routes of Drug Administration:

. Oral route: It

takes approximately 30 minutes for onset of drug effect after drug is swallowed. Oral route allows for use ofmany different dosage forms including tablets, capsules and liquids.

. Intramuscular injection:

Onset of action of drugs injected into muscle occurs rapidly (approximately 5 minutes) because ofhigh blood flow lhrough the muscles.

. Subcutaneous injection: Onset ofaction ofdrugs injected under the skin takes about

l5 rninutes.

. Inhalation:

Gases such as nitrous oxide are absorbed rapidly though the lungs and gain access to the general circulation within 5 minutes.

. Topical: This route includes ointments and creams applied to the skin and mucous
membranes. It is not intended for syslemic drug administration.

. Patch delivery: Onset ofaction ofdrugs in skin patches is about 15 minutes and similar to subcutaneous injection. Skin patches release drug into the blood stream over a

l2 to 24 hour Deriod.

. Habituation
. Tolerance . Addiction . None ofthe above

230
Coplaight e 20ll'2012, Dental Decks

. Oral administration

Subcutaneous injection

. Intravenous injection

. Intramuscular injection

231 Cop)righ O 20ll-2012 - Denbl Decks

Habituation is an acquired tolerance from repeated exposure to a particular stimulus. Psychological and emotional dependence on a drug, tobacco or alcohol result from the repeated use of the substance but without the addictive, physiological need to increase
dosage.

Tolerance is the phenomenon ofdecreased responsiveness to a drug following chronic administration. Note: Physiological dependence is common to all forms ofdrug dependence and abuse. These drugs ofabuse all have the ability lo change one's mood and sensory perception.

trrhen a drug is given intravenously, it is placed directly into the systemic circulation. The drug is delivered rapidly to all tissues, including the drug receptor sites. For all other routes of drug adminrstralion (v)ith the exception of intra-arterial inj ection), the drug must be systemically absorbed prior to distribution to the drug receptor sites, and therefore the onset of pharmacological effects is slower.

IV injection there is a complete (100o/') bio^v^ilabilif. placed into the systemic circulation. With other routes of administraThe entire dose is tion. the drug may be lost prior to reaching the systemic circulation. For example, with first-pass effects, a portion ofar orally administered drug is eliminated, usually through degradation by liver enzymes, before the drug reaches its receptor sites.
.A.lso. rvhen a drug is given by

Remember: The initial distribution ofa drug into the tissues is determined chiefly by the rate of blood flow to the tissue, whereas drug affinity for the tissue will determine
s hether the drug

will concentrate

at that site.

l\,lote: Gastric emptying time and degree of plasma protein binding also have an effect on drug distribution but are less important than the rate ofblood flow to the tissues.

When a drug is administered repeatedly, a higher coneentntion the drug than is desired may be achieved. The effect ofthis excessive accumulation is knorvn as:

of

. Additive effect

Synergistic response

. Cumulative action . Idiosyncrasy

232
Coplrighr O
201

1-2012 - Denial Decks

The Controlled Substsnce Act of 1970 uses which criterio

for inclusion of a drug into one ofthe five schedules?

. Potential for abuse . Medical usefulness . Degree to which it produces physiological dependence . Degree to which it produces physical dependence
. All ofthe above

233
Coptrighr
@

2011-2012 , Denbl

Deck

An additive effect occurs when additive drugs are administered. The response is no greater than that which would be expected had the drugs been given one at a time. There is no enhancement ofpotential ofthe individual drugs as a result ofbeing used in combination.

A synergistic rsponse occurs when the combined action of two drugs is greater than the sum oftheir individual actions. Examples of synergism: Alcohol is synergistic with
diazepam (Valium), narcotics, barbiturates and phenothiazines. taking these drugs.

lt

should be avoided

if

a response to a drug that is unusual or abnormal or one that grossly deviates from the routine reaction.

Idiosyncrasy is

Tle Controlled
1

Substancc Acl

of 1970 uses the following critcria fbr inclusion of

a drug into onc

ofthc fivc schcd-

. PorcntiaL for abuse r'',

oi inportan,

:.
L
.1.

\tcdicaluscfulness
Degfcc to which it produces physiological dcpcndcncc Dclrcc to *hich it produccs physical dcpcndcncc

Remember: Schedule I d gs (LSD, hercin, etc.)@nnot be prescribed and a.c made availablc only for specific approred research pro.jccts. Schedule II drxgs fdmphetanines, noryhirc, cotleine, oxycodone elc.)$n be prescribed but can not be refilled. A ne\\ prcscription mustbcwritten forrefills. Prescriptions lor Schedule II drugs can not bc called into the pharmacy ovcr thc telephone. Schedule III drugs (,,,)d/ocodotie *'ith acetaninophe , cotleine \\'ith arctaninophen, etc.) may be called in to thc pharmacy over the telephonc. Thc prcscribcrcan authorizc rcfills without need ofa new writlcn prcscriplion.

*** Thc prcscribcr must hsve a Drug Enforcement Agency ruthorization nnmber (DEA #) in ordcr lo prcscribc schcdulcd drugs.
Clinical testing ofdrugsr Bcfore
be pcrformcd. Thcrc is thc a drug can be approvcd for salc lo thc public there is a set

ofclinical

tests that must

Pre-Clinical Research Stage. Here the drug is s),nthcsizcd and purified. Animal tcsts arc Dcrformed. and institutional rcvicw boards asscss thc studies and make recommcndations on how to procccd. Ifthc rccommcndations are positivc, thcn an application to the FDA occurs and clinical tesls bcgtn.

'Phase t: clinical studics in this phase represent thc first time that an investigational ncw drug is tested on hu-

mans cithcrhealthy voluntccrs or somctimcs patierts. The purposc ofthcsc studics is study in a clin;cal sctting thc metabolism, structurc-reactivity rclationships. mcchanism ofaction, and side ellccts ofthe drug in humans. lfpossiblc, phasc 1 studies arc uscd to determinc how ellcctivc thc drug is. Phasc I studics are usually conducted on 20

to E0 subiccts. . The purpose of phrse 2 clinical trials is to dctcrminc thc cfficacy ofa drug to trcat patients with a spccific discasc or condition. as well as lcam about common short{crm sidc cffccts or risks. These studics are conducted on a la.gcr scale than phasc I sodics and tlpically involvc scvcml hundrcd patients. . Phase 3 cLinical trials provide morc information about the effects a d safcty ofthe drug and they allow scicntists to cxtrapolate thc rcsults ofclinical studies to thc gcncral population. Phasc 3 studics gcrcrally involvc scvcral hundrcd to scvcral thousand pcoplc. *** After a succcssful phasc III, thc drug company submiis to the Food and Drug Administration 1FD,r/ a Ne\r' Drug Application fND,4/ to markct thc dru8.

'

Which ofthe following refers to the efficacy ofa drug?

. The relative concentrations of two or more drugs that produce the

same drug effect

. The ability ofa drug to produce a desired therapeutic effect regardless ofdosage

. The dose ofa drug that will kill a patient

234
Coplri8ht
@

2011,2012, Denral Decks

. An additive effect

. A synergistic response . An antagonistic effect

. Cumulative action

235
Copyright O 20l l-2012, Denial Decks

*** Efficacy refers

to the number of receptors that must be activated to yield a maximal

response. A drug with high efficacy needs to stimulate only a small percentage ofreceptors, whereas a drug with lesser efficacy (but still considered to be a full agonist) has to activate a larger proportion of receptors.

Factors Goyerning Drug Action: Two factors that determine the effect of a drug on physiologic processes are aflinity and intrinsic activity. Affinity is a measure ofthe tightness that a drug binds to the receptor. Intrinsic activity is a measue ofthe ability ofa drug once bound to the receptor to generate an effect activating stimulus and producing a change in cellular ac-

tivity. Potency is the relative concentrations of two or more drugs that produce the same drug effect. The effect usually chosen is 50% ofthe maximal effect and the dose causing this effect
is called the EC56. Potency is determined mainly by the affinity of the receptor for the drug.

Note: The smaller the 8C56, the greater the potency of the drug. Potency is a comparative term (o e drug is more polent than another drug). Exampl: Drug #l in a dose of l0 mg produces the same magnitude ofresponse as Drug #2 in a dose of 50 mg. The following is true: Drug #l is flrve times as potent as Drug #2. Also: tf Drug #l has a greatr eflicacy than Drug #2, then Drug a greater maximum effect than Drug #2.

#l

is capable ofproducing

When comparing drugs with respect to intensity of response, the drug that produces the greatest maximum effect is the one with the highest ellicacy.

An additive effect occurs when additive drugs are administered. The response is no greater than the sum ofthe individual actions ofeach drug when given alone. There is no enhancement ofpotential ofthe individual drugs as a result ofbeing used in combination.

A synergistic response occurs when the combined action of two drugs having similar pharmacological effects is greater than th sum of the individual actions. Alcohol is s).nergistic with the Valium family ofdrugs fi.e., Valium, Xanax, Halcion, etc), narcotics
and barbiturates. Alcohol should be avoided when takins these medications.