PHARMACOLOGY

TERMS
&
LONG QUESTIONS
SHORT & SMALL (NAUGHTY) TERMs
1. PHARMACOLOGY: is the study of the rule and mechanism of mutual interaction between
drugs and living systems (human species, animal and organism.

2.DRUG: can be defined as chemical agents that uniquely interact with specific target molecules
in the body, thereby producing a biological effect.

3.PHARMACODYNAMICS: Effects of the drugs on biological systems (What a drug does to the
body.

4.PHARMACOKINETICS: Effects of biological systems on the drugs (What the body does to a
drug.

5.Cytochrome P450s enzyme inhibitors: chloramphenicol, ketoconazole, cimetidine

6. Cytochrome P450s enzyme inducers: phenobarbital, rifampicin, carbamazepine

7..hepato enteric circulation(entero-hepaic recycling): Some drugs can be excreted from bile
into duodenum by means of simple diffusion or active transport, and then excreted along with
excrement. Drugs excreted into duodenum by bile can be partially reabsorbed in the intestine,
which forms hepato-enteral circulation.
8.Apparent volume of distribution(Vd):

Vd is defined as the volume in which the amount of drug would need to be uniformly
distributed in according to the blood concentration.

 Vd = D/C

9.half-life, t1/2: Half-life (t1/2) is the time required to change the amount of drug in the body
by one-half during elimination

10. Bioavailability: The rate and extent of absorbtion into the blood circulation following
extravascular administration of drugs.

 F = AUC/Dose
11.Clearance: Volume of blood in a defined region of the body that is cleared of a drug in a
unit time.

 CLT = kel Vd
12. The first-pass effect

Some drugs are inactivated in the gastrointestinal tract and liver before entering into the
systemic circulation. This process called first pass elimination, decreased actual drug
quantity entering into the systemic circulation.

13.elemination rate constant (K):

is a value used in pharmacokinetics to describe the rate at which a drug is removed

from the system.

14. concept of therapeutic effect; is a consequence of a medical treatment of any

kind, the results of which are judged to be desirable and beneficial.

15. adverse effect: is an undesired harmful effect resulting from a medication or other
intervention such as surgery.An adverse effect may be termed a "side effect".
16. Side effects: These are unwanted but often unavoidable pharmacodynamic effects that
occur at therapeutic dose.

17. Toxic effects: These are the result of excessive pharmacological action of the drug due to
overdosage or prolonged use.

18. Allergic reaction: It is an immunological mediated reaction producing symptoms which

are unrelated to the pharmacodynamic profile of the drug and are independent of dosage,
this is also called drug hypersensitivity.eg: penicillins
19. Residual effects: They are defined as the effects occur when the drug concentration is
under threshold after stopping administrating the drug. eg: For instance, drowsiness and
debility occurs in the next morning after administrating

20.Idiosyncrasy: It is genetically determined abnormal reactivity to a chemical.

21.Secondary infection: is that normal flora has been inhibited by antibiotics and the
insensitive flora becomes prominent to cause new infections.

22.Drug tolerance: is said to develop when the response to the same dose of a drug
decreases with repeated uses. Need greater doses of a drug to produce original degree of
effect as time progresses.

23.Physical dependence: An adaptive physiological state produced by repeated use of a drug,

which is characterized by(withdrawal syndromes) if drug administration is stopped.

24.Potency: Potency refers to the amount of drug needed to produce a certain response.

25.Efficacy (Maximal effect): refers to the maximal response that can be elicited by the drug.

26.Psychological dependence: The feeling of satisfaction and psychic drive that require
periodic or continuous administration of the drug to produce a desired effect
（,excite,emotional）or to avoid discomfort.

27.Therapeutic index (TI) :In animal studies, the therapeutic index is usually defined as the
ratio of TD50/LD50 to the ED50 for some therapeutically relevant effect.

28.pd2 :It is a Affinity constant, it is the negative logarithm of the the conc. Of the agonist which
produced 50 % of a maximum. pD2 = -log(KD)

29.pA2 (Antagonist Parameter)

the negative logarithm of the concentration of the antagonist which produced a right shift of the
cumulative dose response curve of agonist to a dose level two-fold as initial one of the drug ..

30.Agonist: It activates a receptor to produce an effect similar to that of the physiological

signal molecule.

31.Antagonist: It prevents the action of an agonist on a receptor but does not have any effect
of its own.

32.partial agonist: has high affinity but low intrinsic activity.It agonizes the receptor at low
dose.While at large dose it antagonizes the effect of agonist. e.g. pentazocine
33."On/off" Effect”: "On/off" Effect Is like a Light Switch ; Without Warning, All of a Sudden,
Person Goes from Full Control to Complete Reversion Back to Bradykinesia, Tremor, Etc.
Lasting from 30 Minutes to Several Hours and Then Get Control Again, On/off" Effect Occurs
after usually after 2 or more years on L Dopa

LONG COMPLICATED (IRRITATING) QUESTIONS

1. Briefly describe the characteristics of zero order kinetics and first-order

First Order Elimination
a. [drug] decreases exponentially w/ time
b. Rate of elimination is proportional to [drug]
c. Plot of log [drug] or ln[drug] vs. time are linear
d. t 1/2 is constant regardless of [drug]
e. Rate = k C
f. C = Co e-kt
g. C vs. t graph is NOT linear, decaying exponential. Log C vs. t graph is linear.
Zero Order Elimination
h. [drug] decreases linearly with time
i. Rate of elimination is constant
j. Rate of elimination is independent of [drug]
k. No true t ½
l. Rate = k
m. C = Co - kt
n. C vs. t graph is LINEAR

2.

3.what is the effect of pilocarpine on the eye and glands as well as clinical uses of pilocarpine ?
1.Eye

 miosis
 decrease intraocular pressure
 cyclospasm
 Pilocarpine mediate contraction of the circular pupillary constrictor muscle and
of the ciliary muscle. Contraction of the pupillary constrictor muscle causes
miosis, a reduction in pupil size.
 Ciliary muscle contraction causes accommodation of focus for near vision.
Marked contraction of the ciliary muscle, which often occurs with cholinesterase
inhibitor intoxication, is called cyclospasm.
 2. Glands secrete increasingly

 Clinical uses of pilocarpine:

1.Glaucoma

Glaucoma is actually a group of diseases that are distinguished by an increase in pressure inside
the eye that causes damage to the optic nerve and to the retina.

 angle-closure glaucoma

 open-angle glaucoma

2.iritis

4.pharmacologicl effect s,mechanism ,clinical uses and major adverse effect of

neostigmine?

 Mechanism of Anticholinesterase agents:

Acetylcholinesterase (AChE) terminates the action of acetylcholine (ACh) at the
junctions of the various cholinergic nerve endings with their effector organs or
postsynaptic sites. Inhibitors of AChE, or anticholinesterase (anti-ChE) agents, cause ACh
to accumulate in the vicinity of cholinergic nerve terminals and thus can produce effects
equivalent to excessive stimulation of cholinergic receptors throughout the central and
peripheral nervous systems.

Pharmacologyical Properties of neostigmine:

Eye

• cause constriction of the pupillary sphincter muscle around the pupillary margin of the
iris (miosis).

• cause constriction of the ciliary muscle (block of accommodation reflex with resultant
focusing to near vision).

• Intraocular pressure falls, as the result of facilitation of outflow of the aqueous humor.

Gastrointestinal Tract

• Neostigmine enhances gastric contractions, increases the secretion of gastric acid

Neuromuscular Junction

• inhibition of AChE at neuromuscular junctions.

 • direct action of neostigmine on skeletal muscle: activation of the N M receptor.

• Promote the release of ACh

Therapeutic Uses

 Paralytic Ileus and Atony of the Urinary Bladder :In the treatment of both these
conditions, neostigmine generally is preferred among the anti-ChE agents.
 Myasthenia Gravis :Myasthenia gravis is a neuromuscular disease characterized by
weakness and marked fatigability of skeletal muscle.
 Myasthenia gravis is caused by an autoimmune response primarily to the ACh
receptor at the postjunctional endplate.
 Administration of anti-ChE agents does not result in subjective improvement in
most congenital myasthenic patients.
 Neostigmine can increase the response of myasthenic muscle to repetitive nerve
impulses, primarily by the preservation of endogenous ACh.

Adverse effects:

 Side effects including: headache, blurred vision , bradycardia etc

5.what is the mechanism of atropine and pralidoxime used to rescue organophosphate

intoxication?

Mechanism Organophosphate intoxication:

Irreversible anticholinesterase agents

• insecticide

• nerve gas

Atropine in sufficient dosage effectively antagonizes the actions at muscarinic receptor sites,
and to a moderate extent, at peripheral ganglionic and central sites.

 Atropine should be given in doses sufficient to cross the blood–brain barrier.

 2 mg should be given every 5–10 minutes until muscarinic symptoms disappear, or until
signs of atropine toxicity appear.

 Atropine is virtually without effect against the peripheral neuromuscular compromise,

which may be reversed by pralidoxime: a cholinesterase reactivator.
  AChE reactivators are beneficial in the therapy of organophosphorus anti-ChE
intoxication, but their use is supplemental to the administration of atropine.

6.Pharmacodynamics and therapeutic applications of cholinoceptor blocking drugs:

atropine;?
Pharmacological effect :
Central Nervous System

 Atropine in therapeutic doses (0.5–1 mg) →mild vagal excitation.

 toxic doses → restlessness, irritability, disorientation, hallucinations, or delirium.

Cardiovascular Syetem -Heart

 Larger doses of atropine cause progressively increasing tachycardia by blocking

vagal effects on M2 receptors on the SA node.
 Moderate to Large doses: increase heart rate

Eye
 Dilated pupils (mydriasis)
 Decreased accommodation due to paralysis of ciliary muscles (cycloplegia)
Gastrointestinal(GI)
• Relax smooth muscle tone of GI tract
• Decrease intestinal and gastric secretions
• Decrease motility and peristalsis
Genitourinary:
• Relaxed detrusor muscle
• Increased constriction of internal sphincter
• Result: urinary retention
Biliary Tract

• Atropine exerts a mild antispasmodic action on the gallbladder and bile ducts.

Sweat Glands and Temperature

• Small doses of atropine or scopolamine inhibit the activity of sweat glands innervated by
sympathetic cholinergic fibers, making the skin hot and dry.
Circulation

• Most vessels lack cholinergic innervation. However, in clinical doses, atropine

completely counteracts the peripheral vasodilation and sharp fall in blood pressure
caused by choline esters.
 • Atropine in toxic, and occasionally therapeutic, doses can dilate cutaneous blood
vessels.

Respiratory Tract

• Atropine inhibit secretions of the nose, mouth and bronchi → dry the mucous
membranes of the respiratory tract.

• Atropine inhibit bronchoconstriction caused by histamine and bradykinin → useful in

the treatment of asthma.

Therapeutic Uses of Antimuscarinic Agents:

1. Uses in Anesthesia

Atropine commonly is given to block responses to vagal reflexes induced by surgical

manipulation of visceral organs.
2.) Anticholinesterase Poisoning
The use of atropine in large doses for the treatment of poisoning by anticholinesterase
organophosphorus insecticides. Atropine also may be used to antagonize the
parasympathomimetic effects of pyridostigmine or other anticholinesterase agents
administered in the treatment of myasthenia gravis.

7.what is the mechanism ,action ,characteristic and clinical uses of depolarizing muscular
relaxants such as suxamethonium and non depolarizing muscular relaxant such as
tubocurarine?
Nictinic receptor antagonist:

Mechanism:

Competitive antagonists competitively block the binding of ACh to the nicotinic ACh receptor at
the end plate. The depolarizing agents depolarize the membrane by opening channels in the
same manner as ACh. However, they persist for longer durations at the neuromuscular junction
because of their resistance to AChE.

pharmacological charecterstics:

Skeletal Muscle

Sequence and Characteristics of Paralysis

Following intravenous administration of a competitive antagonist, motor weakness

progresses to a total flaccid paralysis.
 Small, rapidly moving muscles (e.g., those of the eyes, jaw, and larynx) → the limbs and
trunk → intercostal muscles → diaphragm are paralyzed → respiration ceases.

 After a single intravenous dose of 10–30 mg of a depolarizing agent such as

succinylcholine, muscle fasciculations occur briefly; relaxation occurs within 1 minute,
becomes maximal within 2 minutes, and generally disappears within 5 minutes. Muscle
relaxation of longer duration is achieved by continuous intravenous infusion.

Cardiovascular System

 Blood pressure may be decreased

 Changes in heart rate. Mild tachycardia
 More severe reactions include marked hypotension, constipation, syncope, paralytic
ileus, urinary retention, and cycloplegia.
 Therapeutic Uses

 Neuromuscular blocking agents are used mainly in surgical anesthesia to relax skeletal
muscle, particularly of the abdominal wall, to facilitate operative manipulations

 Neuromuscular blocking agents of short duration often are used to facilitate

endotracheal intubation and have been used to facilitate laryngoscopy, bronchoscopy,
and esophagoscopy in combination with a general anesthetic agent.

8.what is the pharmacological effect ,clinical uses and adverse effect of norepinephrine
,epinephrine ,dopamine and isoprenoline ?

Pharmcalolgical effect Epinephrine (Epi), Norepinephrine, Dopamine, Isoproterenol:

 The heart rate↑; cardiac output is enhanced

 Epi relaxes GI smooth muscle
 Beneficial effects of Epi in asthma:Bronchodilatation (acting at β2 receptors on bronchial
smooth muscle).
 Epi raises the plasma concentration of free fatty acids by stimulating β receptors in
adipocytes.
 The concentrations of glucose and lactate in blood↑
 In response to infused NE, systolic and diastolic pressures, and usually pulse pressure,
increase.
 At low concentrations smooth muscle vasodilation.
 At higher concentrations, DA acts on cardiac β1 receptors to produce a positive
inotropic effect.
  DA also causes the release of NE from nerve terminals, which contributes to its effects
on the heart.
 At high concentrations, DA activates vascular α1 receptors, leading to more general
vasoconstriction.
 In Isoprenaline Diastolic pressure falls. Systolic blood pressure may remain unchanged
or rise; mean arterial pressure typically falls.
 Cardiac output increases due to the positive inotropic and chronotropic effects of the
drug

Clinical uses of Epinephrine (Epi), Norepinephrine ,Dopamine, Isoprenaline:

• A major use is to provide rapid relief of hypersensitivity reactions, including anaphylaxis,

to drugs and other allergens.
• prolong the action of local anesthetics.
• restore cardiac rhythm in patients with cardiac arrest.
• In the treatment of shock
• In the treatment of low blood pressure
• Dopamine is used in the treatment of severe congestive failure, particularly in patients
with oliguria and low or normal peripheral vascular resistance.
• The drug also may improve physiological parameters in the treatment of cardiogenic
and septic shock.
• Isoproterenol may be used in emergencies to stimulate heart rate in patients with
bradycardia or heart block.

Adverse effect Epinephrine (Epi),Norepinephrine , Isoprenaline:

• restlessness,headache, tremor, and palpitations.

• More serious reactions include cerebral hemorrhage and cardiac arrhythmias.
• Excessive doses cause severe hypertension.
• necrosis and sloughing occur at the site of intravenous injection owing to extravasation
of the drug.
• Reduced blood flow to organs such as kidney and intestines.
• Palpitations, tachycardia, headache, and flushing are common. Cardiac ischemia and
arrhythmias may occur, particularly in patients with underlying coronary artery disease.

9.what are the classification of alpha receptor antagonist?

• The α1 adrenergic receptors mediate contraction of arterial and venous smooth muscle.

• The α2 receptors are involved in inhibiting the release of NE from nerve endings, and
regulating metabolic effects.
 10.what are the major pharmacological effect and clnical uses of alpha recptor antagonist?

Pharmacological effect and therapeutic effect:

1. Phenoxybenzamine (PBZ)

 PBZ causes a progressive decrease in peripheral resistance,

 increase in cardiac output
 enhanced release of NE (due to α2 blockade).

Therapeutic effect:

 A major use of PBZ is in the treatment of pheochromocytoma,

 tumors of the adrenal medulla
 PBZ is almost always used to treat the patient in preparation for surgical removal of the
tumor.

Phentolamine and Tolazoline

 Phentolamine is a competitive α receptor antagonist that has similar affinities for α1

and α2 receptors. Its effects on the cardiovascular system are very similar to those of
PBZ.

Therapeutic Uses

 Phentolamine can be used in short-term control of hypertension in patients with

pheochromocytoma.
 Phentolamine has been used locally to prevent dermal necrosis after the inadvertent
extravasation of an α receptor agonist.

Prazosin

 Prazosin is a potent and selective α1 receptor antagonist.

 With little or no α2 receptor–blocking effect at concentrations achieved clinically,
prazosin probably does not promote the release of NE from sympathetic nerve endings
in the heart.
Therapeutic effect :
 Prazosin frequently is used for the treatment of hypertension. The major effects of
prazosin result from its blockade of α1 receptors in arterioles and veins

Yohimbine :Yohimbine is a competitive α2 antagonist.

Yohimbine blood pressure and heart rate; it also enhances motor activity and produces
tremors.

11.what are the major pharmacological effect ,clinical uses and adverse effect of beta_receptor
antagonist?

12.What are pharmacological effect and therapeutic uses and adverse reaction of
Benzodiazepines?
 Pharmacological effects &Therapeutic Uses
1. Antianxiety
– Diazepam reduces anxiety at doses that do not produce sedation by inhibiting
the neuronal circuits in the limbic system of the brain (hippocampus,
amygdala)
Applications
 anxiety of generalized anxiety disorder
 Patients with panic attack syndrome

2.Sedation and hypnosis

– Shortens the latency of sleep onset

– Decreases intermittent awakening

– Prolongs the duration of sleep

– High TI value

– Prolongs the NREM

– Little effects on REM

– dependency

Applications

 Sleep disorders

. 3. Anticonvulsant effects and antiepileptic effects

-Inhibits the development and spread of epileptiform activity in the CNS

Applications
  Tetanus, eclampsia, convulsion

 Diazepam is the drug of primary choice in terminating status epilepticus

4. Muscle relaxation

– Low dose: inhibitory effects on polysynaptic reflexes and internuncial transmission

– High dose: depress transmission at the skeletal myoneural junction

Applications

 Sleletal muscle spasms

 Spasticity from degenerative disorders (multiple sclerosis and cerebral palsy)

Therapeutic Uses:

1. Anxiety Disorders

2. Insomia

3. Anticonvulsion and antiepilepsy

4. Muscular disorders

Adverse reactions

1. Drowsiness,syncope,fatigue,cognitive impairment

2. High dose:ataxia

3. CNS-depressant effects are potentiated in combination with alcohol, even

fatal respiratory depression may occur

13.what are the pharmacological efect and charecteritic of phenytoin,phenobarbitone ,

ethosuximide ,benzodiazepines , sodium valproate and carbamazepine ?

1.Sodium phenytoin:

 Function and mechanisms:

 Prevents post-tetanic potentiation

 Limits development of maximal seizure activity
 Reduces the spread of seizures
 -blocks Na+ -channel
 blocks T type Ca2+ -channel
 Therapeutic use:

1. epilepsy

 Generalized tonic-clonic;
 partial seizure (first choice )
 absence seizures inefficacy ;

2. trigeminal and related neuralgias

3. arrhythmia

Adverse reaction:

 Local stimulation：nausea、vomitting
 CNS response: headaches
 Blood system: vitamin K and folate deficiency,loss of libido
 Allergic respose: rash, blood dyscrasias

2.carbamazepine:mechanism is identical to phenytoin.

3.Phenobarbital:

 Primidone is converted to phenobarbital after biotransformation

 Partial onset and secondarily generalized seizures
 Sedation, dizziness, nausea

4.Ethosuximide:

 Quick absorbtion, long t1/2(18-72 hr)

 reduceT-type Ca2+-channel
 Absence seizure (pure petit mal)
 Drug interaction with valproic
 Drowsy,dizzy,gastrointestinal tract reaction, agranulocytosis，aplastic anemia

5.Benzodiazepine: Diazepam：status epilepticus (first-choice)

6. Sodium valproate:

 All types of epilepsy

 Inhibit GABA-degrading enzymes
 Stimulate glutamate-degrading enzymes
 Block Na+-channels
 Tremor, appetite stimulation
14..what are t he types an the mechanism of antiparkinsonin drugs?

Mechanism:

 Loss of Dopaminergic (DA) Cells Located in Basal Ganglia; most

symptoms do not appear until striata DA levels decline by at least 70-80%.
 theory of dopamine: in the nigrostriatal pathway dopaminergic neurons
degeneration. DA concentration
 Imbalance primarily between the excitatory neurotransmitter Acetylcholine
and inhibitory neurotransmitter Dopamine in the Basal Ganglia
 Most cases of idiopathic Parkinson’s are believed to be due to a
combination of genetic and environmental factors.
 Environmental risk factors associated with the development of PD include:
 use of pesticides,
 living in a rural environment,
 consumption of well water, exposure to herbicides,
 and proximity to industrial plants or quarries.

Antiparkinsonian Drugs:

Dopaminergic agents ：

Levadopa

Carbidopa

Tolcapone,entacapone

Selegiline

amantadine

Anticholinergic agents:

Benzhexol (artane )

Kemadrine

benzatropine

15.what is the pharmacologic effect and clinical uses of levodopa?

Ans:

Pharmacodynamics:
1. Supply DA first choice

2) improvement in rigidity、 bradykinesia；

3) act slowly,duration is longer;

4) Hepatic coma

Pharmacokinetics
1、po---absorb rapidly from small bowel，
influence factors:
1）gastric emptying absorption
2）food of high protein F

2、 mostly peripheral decarboxylation

(by DC) DA ;  1%  CNS .
3、used with DC inhibitors effects ，
adverse reactions

Adverse reactions:

1. Early reactions

1) gastrointestinal ~ (80%): anorexia, nausea and vomitting

2) cardiovascular ~ hypotension (30), tachycardia.

2. Long term reactions

1）Abnormal limb movements: hyperkinesia

2） on - off effect

 on-time: full symptom control

 off-time: periods of reduced voluntary movement

3） psychiatric symptoms: agitation, anxiety, elation and insomnia, mental

confusion (10-15%)
16.what is the mechanism of levodopa used with carbidopa?

2. Carbidopa
 Peripheral decarboxylase inhibitor
 Prevents levodopa’s metabolism in peripheral
system
 Carbidopa: levodopa (1:4)

17.What are pharmacological effects of antipsychotic drugs such as chlorpromazine?

Pharmacologic Effects :
 blocking effects at a wide range of receptors, including dopamine and a
adrenoceptor, M, H1 histaminic, and serotonin (5-HT2) receptors.
 a wide variety of central nervous system, autonomic, and endocrine effects.

1.1 Sedative and anti-anxiety effects

A. Psychotic patients: prominent effects

B. Normal subjects: NOT

1.2 Effects on conditioned response ;Selectively inhibit conditioned response

1.3 Antipsychotic effects :Block dopaminergic receptors in brain and periphery

1.4 Anti-emetic effect

Most antipsychotics protect against the nausea- and emesis induced by apomorphine or
some disease such as tumor.

 Block central dopaminergic receptors in the chemoreceptor trigger zone (CTZ) of

the medulla.

 Large doses inhibit the vomiting center directly.

 1.5. Effects on body-temperature regulation :Inhibit temperature-regulating center

in hypothalamus

Can be used at artificial hibernation

1.6 Effects on autonomic nerve system

 Block 5-HT2 receptors

 Block 1 adrenergic receptors

1.7 Endocrine Effects

 Antagonizing D2-receptor in mammotrophic cells in the anterior pituitory, causing

release of more prolactin and indution of lactation

 Inhibiting corticotropin-releasing hormone (CRH), resulting decreased release of

glucocorticoids

1.8 Potentiation of other CNS depressive agents

eg. Sedatives

Therapeutic applications:

2.1 Treatment of Schizophrenia:Eliminating delusions, hallucinations

2.2 Prevention of nausea and vomitting :Vomiting caused by morphine, estrogen and also
by radiation sickness

2.3 Hibernation therapy:Chlorpromazine, promethazine, pethidine

Adverse Reactions:

 A. Behavioral Effects : drug-induced akinesia

 A. Extrapyramidal reactions :occurring early during treatment with older agents
 Parkinson's syndrome
  akathisia (uncontrollable restlessness)
 acute dystonic reactions (spastic retrocollis or torticollis)
 C. Autonomic Nervous System Effects :
antimuscarinic adverse effects: urinary retention
adrenoceptor-blocking actions: postural hypotension

18.What are pharmacological effects of opioids?

Morphine
• Morphine activates opiate receptor to produce analgesic effect like endogenous
opiate peptides.
• high affinity for μ receptors
• varying affinities for δ and κ receptors
• low affinity for σ receptors in CNS and gastrointestinal tract.*
• The structure of morphine consists of five rings forming a T-shaped molecule
• good absorption from gastrointestinal tract
• significant first-pass effect
• subcutaneous injection is commonly used.
• rapidly entering to all body tissues, including fetuses of pregnant women.
• Conjugation with glucuronic acids and excreted from kidney

I.Organ System Effects of Morphine:

A. Central nervous system effects

1) Analgesia
 strong analgesia , effective on various pains , chronic dull pain, colic and
acute sharp pain, and no effect on other senses and consciousness.
2) Sedation:relieving anxiety and stress accompanied with severe pain.
3) Respiratory depression:reduce response of respiratory centers to blood CO2
4) Cough suppression: direct inhibition of cough center.
5) Emesis: direct stimulation of CTZ to cause nausea and vomiting.
6) Miosis: stimulating Edinger-Wesphal nucleus, pinpoint pupils are indicative of
toxic dosage.
II.Peripheral effects
1) Cardiovascular system
No significant direct effects on the heart;but vasodilation
2.. Histamine release: bbronchoconstriction

3.. Effects on smooth muscles:

1) relieves diarrhea or causes constipation

 reducing peristalsis and stomach mobility

  increasing spasmodic nonpropulsive contraction

 decreasing biliary and pancreatic secretions to cause indigestion.

2 increasing biliary pressure by constriction of Oddi's sphincter to induce biliary colic.

III. Therapeutic uses

1. Pain: acute pain and chronic pain.
2. Dyspnea
vasodilation
sedative
inhibiting respiration
3. Diarrhea: causing constipation
4. Anesthesia

IV. Adverse reactions

1. Tolerance
2. Dependence;Physical dependence AND Psychological dependence

19.Why can morphine be use to acute pulmonary edema patients?

 Relieve shortness of breath and anxiety during pulmonary edema associated with left
ventricular failure
 The mechanism is not clear, but the Proposed mechanisms include reduced anxiety
(perception of shortness of breath)
 Reduced cardiac preload (reduced venous tone)
 Reduced afterload (decreased peripheral resistance)
 Particularly useful when treating painful myocardial ischemia with pulmonary edema
20.what is the common mechanism of Antipyretic-analgesic and anti-inflammatory drugs
or nonsteroidal anti-inflammatory drugs (NSAIDs) ?

Antipyretic-analgesic and anti-inflammatory drugs or nonsteroidal anti-inflammatory

drugs (NSAIDs) mechanism;are a class ofdrugs that provides analgesic (pain-killing)
and antipyretic (fever-reducing) effects, and, in higher doses, anti-inflammatory effects

 NSAIDs: inhibit cyclooxygenase (COX) and reduce the production of PGs

1. Antipyretic effect

• Body temperature regulation

Mechanism: inhibit synthesis of PGs in the CNS

• Characteristics They only decrease the body temperature of those who have a fever
and no effect on normal ones.
2.Analgesic Effect:

Cause of pain: in site of tissue injury or inflammation some chemical algesiogenic

substances are produced and released such as bradykinin and so on together with PGs.

• Bradykinin (BK): cause pain through stimulating the algesireceptors directly.

• PG: (1) hyperalgesia

(2) PG(E1 E2 F2a) also have algesiogenic effect

Mechanism:

inhibit the synthesis of PGs in periphery

Characteristics:

• Only effective to mild to moderate pain.

• Non-narcotic and no euphoria.

• No respiratory inhibition.

3.Anti-inflammatory Effect:

♣ The role of PGs in inflammation

1. cause vasodilation and tissue edema

2. coordinate with bradykinin to cause inflammation

♣ Mechanism of anti-inflammatory effect

(1) Reducing biosynthesis of prostaglandins by inhibiting COX.

(2) inhibition of the expression of some cell adhesion molecules

(3) Additional possible mechanisms

– inhibition of leukocyte chemotaxis

– down regulation of interleukin-1 production

– decrease the production of free radicals and superoxide

– interference with calcium-mediated intracellular events

Characteristics: NSAIDs only relieve the main clinical symptoms (erythema, edema, fever,
pain and dysfunction) of inflammation, but have no effect on the autoimmunological
process of rheumatic and rheumatoid arthritis.

21.What are pharmacological effect and therapeutic uses oand adverse effect of aspirin?
 It is widely used analgesic-antipyretic-anti-inflammatory agent with potent
antiplatelet effects.
 Hydrolyzed rapidly to acetic acid and salicylate by esterases and Salicylates are
metabolized by cytochrome P450 in the liver.
 Urine pH have a strong influence on the excretion amount of free salicylate from
kidney so we can reduce the blood concentration of free salicylate through
alkalizing the urine
 Pharmacological Effects
1. Antipyretic and analgesic effect
2. Ant-inflammatory and antirheumatic effect
3. Inhibit platelet aggregation and preventthrombosis
Platelet COX-1: TXA2 synthetase (Acetylation of Cyclooxigenase in Platelet) endothelium
COX-1: PGI2 synthetase
Short life only 8-11days and no protein biosynthesis capacity compared with vascular
endothelium
Aspirin administrated in low dose can reduce TXA2(Thromboxane A2) remarkably but have
no apparent influence on PGI2
 Therapeutic Applications
1. Antipyresis and analgesia
 Headache, toothache, myalgia, neuralgia, dysmenorrhea and fever of influenza.
2. Anti-inflammation and antirheumatism
 Diagnosis and therapy of acute rheumatic fever
 Rheumatic and rheumatoid arthritis to relieve the symptoms.
3. Antithrombosis
 It can reduce mortality and re-ischemia.
 In transient ischemic attack patients to prevent cerebral thrombosis.
in angioplasty, bypass transplant operations to prevent thrombosis.
Adverse efeect:
1. nausea and vomiting
2. Gastric ulcer
3. Blood Coagulation Disorders
4. Allergy
5. Salicylism
6. 5. Reye’s syndrome: Severe hepatic dysfunction with complication of encephalopathy..
Substitute aspirin with acetaminophen

22.THE EFFECT AND MECHANISM OF LOCAL ANESTHETICS?

Ans: EFFECT:

 When applied locally to nerve tissue in appropriate concentrations, local anesthetics can
act on any part of the nervous system and on every type of nerve fiber, reversibly
blocking the action potentials responsible for nerve conduction.
 A local anesthetic in contact with a nerve trunk can cause both sensory and motor
paralysis in the area innervated. These effects of clinically relevant concentrations of
local anesthetics are reversible with recovery of nerve function and no evidence of
damage to nerve fibers or cells in most clinical applications.
Mechanism of Action:
Local anesthetics block conduction by decreasing or preventing the large transient
increase in the permeability of excitable membranes to Na+ that normally is produced
by a slight depolarization of the membrane.
This action is due to direct interaction with voltage-gated Na+ channels.

23.THE FACTORS THT INFLUENCE THE EFFECT OF LOCAL ANESTHETICS?

 ANS: Nerve membrane (Na+,K+ pump)

 Conduction block
 Myelin:Lipid insulating material covering some nervesImpulses travel fast along the
myelin to nodes.
 pKa and pH effects
 5. Toxicity.