DIAMS

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 DIAM S
PHARMACOLOGY
Contents
1. General Pharmacological principles...........................................3
• Pharmacokinetics
• Pharmakodynamics

2. Drugs Acting on Autonomic Nervous System........................... 10

• ANS: General considerations
• Cholinergic system & drugs
• Anticholinergic drugs
• Adrenergic system & drugs
• Antiadrenergic drugs

3. Autacoids and Related Drugs...................................................... 21

• Prostaglandins, Leukotrienes
• Nonsteroidal Antiinflammatory Drugs
• Drugs used for Rheumatoid Arthritis and Drugs for Gout
• Antihistaminics
• 5-Hydroxytryptamine, its antagonists & Drug therapy of Migraine

4. Respiratory System Drugs................ ........................................... 26

• Drugs for Bronchial Asthma

5. Hormones and Related Drttgs..................................................... 29

• Insulin & Oral Hypoglycaemic Drugs
• Thyroid hormones & Thyroid Inhibitors
• Corticosteroids

6. Drugs Acting on Central Nervous System................................ 35

• Sedatives-Hypnotics
• Antiepileptic drugs
- • Anti Parkinsonian drugs
• Drugs used in mental illness: Antipsychotic and Antianxiety Drugs
• Drugs used in mental illness: Antidepressant and Antinianic Drugs
•; Opioid Analgesics and Antagonists

7. Cardiovascular Drugs........................................... ...................... 44

• Antihypertensive Drugs
•' Antianginal and other Anti-ischaemic Drugs
• Cardiac Glycosides & Drugs for CHF
• Antiarrhythmic Drugs
8. Drugs Acting on Kidney.............................................................. 54
• Diuretics

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 DIAMS
PHARMACOLOGY
9. Drugs Affecting Blood.................................... .57
M • Drugs affecting coagulation, Bleeding and Thrombosis

10. Gastrointestinal Drugs.................................... .60

• Drugs for Peptic Ulcer
• Emetics, Antiemetics and other Gastrointestinal Drugs

11. Antimicrobial D rugs....................................... 64

• Antimicrobial Drugs: General considerations
• Inhibitors o f Cell wall synthesis
• Inhibitors o f Protein synthesis
• Inhibitors o f Metabolism
• Inhibitors o f DNA synthesis
• Antitubercular Drugs
• Antileprotic Drugs
• Antifungal Drugs
• Antiviral Drugs
• Antimalarial Drugs
• Antiamoebic & Other Antiprotozoal drugs
• Antihelmintics

12. Chemotherapy of Neoplastic Diseases......... 86

• Anticancer Drugs
' Y

13. Immunopharmacology.................................... .91

• Immunosuppressants
• Immunomodulators

14. Chelating Agents.............................................. 93

15. Clinical Manifestations of Adverse Reactions to Drugs...... 94

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 DIAMS 3
2005 PHARMACOLOGY
GENERAL PHARMACOLOGY III

PHARMACOLOGY - Science of drugs

Routes of drug administration
1. Oral
Advantages: Safer, convenient & economical
Disadvantages: Can cause nausea, vomiting
Irritant & unpalatable drugs cannot be given orally
Highly polar drugs are not absorbed
Some drugs are destroyed by gastric juice
Some drugs go rapid first pass metabolism in liver
2. Sublingual
3. Cutaneous
4. Nasal
5. Inhalational
6. Topical
7. Rectal
8. Parenteral
{Subcutaneous, Intravenous, Intramuscular, Intradermal, Intrathecal, Intraarticular,
Intracardiac)

PHARMACOKINETICS
*What the drug does to the body’
Quantitative study o f drug movement in, through and out o f the body
Includes - Absorption, Distribution & tStqfhge, Biotransformation (metabolism), Excretion

A. ABSORPTION
• Factors affecting absorption: Transport o f drug
o Dosage form o f the drug (aqueous solubility) 1. Passive diffusion & filtration
o Route o f administration 2. Specialized transport
o Drug particle size - Active transport
o Concentration o f the drug - Facilitated transport
o Lipid-water coefficient of the drug - Pinocytosis
o Degree o f ionization
o Area o f absorbing surface
o Vascularity o f the absorbing surface

• Lipid soluble nonelectrolytes (ethanol) are readily absorbed from stomach & intestine
• Acidic drugs (eg: Salicylates, Barbiturates) remain unionized in stomach and are hence absorbed
• Basic drugs ionize in stomach and are absorbed only on reaching the duodenum
• Highly ionized drugs eg: streptomycin, neostigmine are poorly absorbed when given orally
• Presence o f fo o d dilutes the drug and retards absorption, or form complexes with food constituent
• Luminal effect- formation of insoluble complexes with other concurrently ingested drugs
(eg: Tetracyclines with iron preparations, Phenytoin w ith sucralfate)
• Vasoconstrictors eg: adrenaline, injected with the drug retard absorption
• Systemic absorption after topical application depends on lipid solubility of drugs

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BIOAVAILABILITY:
• It is a measure of the fraction of administered dose of a drug the reaches the systemic circulation
• It is determined by the area under the plasma concentration - time curve in blood or by its
excretion in urine
• Bioavailability o f the drug injected intravenously (i.v.) is 100%

B. DISTRIBUTION
Distribution of a drug into the tissues is determined by
o Lipid solubility
o Capillary permeability
o Presence o f tissue barrier (Blood brain barrier, Blood placental barrier, blood-testicular barrier)
o Plasma protein binding
o Blood flow in tissues

Volume of distribution (V) = Dose administered i.v.

Plasma concentration
The volume of body water in which, the drug appears to be distributed, after administration is known
as its volume o f distribution.

PLASMA PROTIEN BINDING

Drugs exist in plasma in two forms:
1. Free form (pharmacologically active)
2. Protein bound (pharmacologically inactive)

• Acidic drugs generally bind to plasma albumin, Basic drugs to ai acid glycoprotein
• As concentration o f drug increases over therapeutic r^ § e ^ N
$r<^tein binding sites are
progressively saturated, so free form of drug increases ^ '
• Highly plasm a protein bound drugs are restricted to vascular compartments, So they have lower
volume o f distribution
• The bound form is neither available for metabolism nor for excretion and not for action
• Binding sites are non-specific, one drug can bind to many sites o f protein, or more than one
drug can bound to same site. So drug bound with higher affinity will displace that bound with
lower affinity. (Sulfonamides & Vit K displace bilirubin - kernicterus in neonates)
• In hypoalbuminemia the binding sites are reduced and leads to high concentration of free drug
• In inflammatory diseases & in pregnancy, acute phase reactant a l acid glycoprotein increases,
so binding increases.

TISSUE STORAGE
o Liver - Chloroquine, tetracyclines
o Kidney - Cd, Pb, Hg
o Eye - Chloroquine
o Bone & teeth - Lead, tetracycline
o Lung - M ethadone, amphetamine, CPZ
o Fat - Thiopentone
o Skeletal muscles, heart - Digoxin, Emetine
o Thyroid - Iodine

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2005 PHARMACOLOGY
C. BIOTRANSFQRMATION (METABOLISM)
Biotransformation - chemical alteration of the drug in the body
Primary site - Liver (Others are - kidney, intestine, lungs)

Biotransformation reactions:
1. Nonsynthetic (Phase I) - Oxidation, reduction, hydrolysis
2. Synthetic (Phase II) - Glucoronide conjugation, Acetylation, methylation, Sulfate / glycine /
gluthathione conjugation, Ribonucleoside/nucleotide synthesis

Biotransformation o f drugs can lead to:

1. Inactivation 2. Active metabolite from an active drug (PRODRUG) 3. Activation of inactive drug
PRODRUGS: Levodopa - Dopamine
Enalapril - Enalaprilat
Sulfasalazine - 5-Aminosalicyclic acid
Zidovudine - Zidovudine triphosphate
Cortisone - Hydrocortisone

Drugs metabolizing enzymes:

1. Microsomal —Located on smooth ER of hepatic cells & other tissues
Include Monooxygenases, Cytochrome P450, Glucoronyl transferase
Inducible by drugs
2. Nonmicrosomal - located in the cytoplasm and mitochondria o f hepatic cells & other tissues
Include - oxidases, esterases, amidases, conjugases
^ N ot inducible by drugs
3. Hofmann elimination - Inactivation of drug by molecular rearrangement without any enzyme
(eg: Atracurium)
Microsomal enzyme induction: ' :V\X ^
• Enzyme inducers: Rifampicin, Phenobarbitone, Phenytoin, Griseofulvin, Phenylbutazone,-
Chloral hydrate, etc
• These drugs decrease intensity and/or duration o f action o f drugs that are inactivated by
metabolism or may develop tolerance (autoinduction)
• Drugs whose m etabolism is significantly affected by enzyme induction - Anticoagulants, OCP,
Steroids, Hypoglycaemics, Antivirals, Anticonvulsants

Inhibition o f drug m etabolism

• Enzyme inhibitors: Ketoconazole, Cimetidine, Erythromycin, Metronidazole, Allopurinol,
Sulphonamides, Quinidine, etc
• These drugs increase the levels or intensity or duration o f action of the drugs whose
metabolism is inhibited, i.e. increases toxicity of the object drug

FIRST PASS METABOLISM

• This refers to m etabolism o f a drug during its passage from the site of absorption into the
systemic circulation i.e. in the intestinal wall and liver (where they first reach through the portal
vein), so that the amount reaching the systemic circulation is less than the amount absorbed
• All oral administered drugs undergo first pass metabolism
e.g: Nitrates, lidocaine, pethidine undergo very high first pass metabolism
• Routes which AVOID first pass metabolism - Sublingual, Intravenous, rectal, transdermal

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2005 PHARMACOLOGY

4. EXCRETION
Excretion is the passage out o f systemically absorbed drug
Channels of excretion: - Urine, Faeces, Exhaled air, Saliva & sweat, m ilk

RENAL EXCRETION
1.Filtration -
• Depends on plasm a protein binding & renal blood flow
• Drugs are filtered through the glomerulus along with other plasm a constituents
• Drugs, highly bound to plasma proteins or having large m olecular size are filtered very slowly
2. Tubular reabsorption
• Depends on lipid solubility and ionization of the drug at the existing urinary pH
• Lipid soluble, unionized drugs are reabsorbed, but non-lipid soluble drugs, ionized are not
• Weak bases ionize more and less reabsorbed in acidic urine
• Weak acids ionize m ore and are less reabsorbed in alkaline
• This principle is used for increasing the excretion o f drug in poisoning e.g. the urine is
alkalinized in barbiturate and salicylate poisoning while it is acidified in morphine &
amphetamine poisoning
3. Tubular secretion
• This is active transfer o f organic acids (penicillin, probenecid, uric acid, salicylates, Mtx) and
organic bases (thiazides, quinine, procanamide) by two separate non-specific processes.
• Drugs utilizing the same active transport compete with each other e.g.
i. Probenecid blocks the active transport of penicillin, decreasing its excretion, hence fes
duration o f action. It also increases the excretion o f uric acid by blocking its reabsorption
ii. Salicylates block uricosuric action of probenedd^qnd^ sulfinpyrazone
iii. Quinidine decreases renal excretion of digoxin > \

KINETICS OF ELIMINATION
Clearance (CL): The clearance o f a drug is the theoretical volume o f plasm a from which the drug is
completely removed in unit time (analogy creatinine clearance)

Clearance (CL) = Rate o f elimination / Plasma concentration

PLASMA HALF-LIFE
The plasma half-life o f a drug is the time taken for its plasma concentration to be reduced to half of its
original value
1 1'/2 - 50% drug is eliminated
2 t'A - 75% (50 + 25) drug is eliminated
3 t */2 - 87.5% (50 + 25 + 12.5) drug is eliminated
4 1Vi - 93.75% (50 + 25 + 12.5 + 6.25) drug is eliminated
Thus, nearly complete drug elimination occurs in 4-5 half lives

First order kinetics

o The rate of elimination is directly proportional to drug concentration
o A constant fraction o f drug present in the body is eliminated in unit time
o CL and V does not change
o tVi remains constant

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Zero order kinetics
o The rate o f elimination remains constant irrespective of drug concentration
o A constant amount o f drug is eliminated in unit time
o CL decreases with increase in concentration
o t'A increases with dose
eg: Ethyl alchohol, Phenytoin, W afarin, Tolbutamide, Theophylline, Aspirin, Propronalol

PHARMAKODYNAMICSl*•
‘What the drug does to the body’
Includes - physiological & biochem ical effects of drugs and their mechanism o f action.

MECHANISM OF ACTION
1. Physical action
2. Chemical action
3. Through enzymes
• Stimulation
• Inhibition - Non-specific
Specific (Competitive, Non-competitive)
4. Through receptors

RECEPTORS
Receptor is a specific binding site with functional correlate

> o Affinity: The ability of the drug to combine with the receptor
o Intrinsic activity: The ability o f the drug to activate the receptor consequent to receptor occupation
\ s." ' .
V Vv •s
Agonists: Have both affinity and maximal intrinsic activity (IA=1), eg: adrenaline, histamine, morphin
Antagonists: have affinity but no intrinsic activity (IA=0), eg: Propronalol, atropine, naloxone
Partial agonists: Have affinity and submaximal intrinsic activity (IA between 0 & 1) eg: Nalorphine
Inverse agonist: Have affinity but intrinsic activity with a minus sign (IA= between 0 & -1)
eg: P- carboline

Transducer mechanisms
Mechanisms of translation o f receptor activation into functional response are: -
1. G-protein coupled receptors
• Adenylyl cyclase: cAM P pathway
• Phospholipase C: IP3-DAG pathway
• Channel regulation
2. Receptors with intrinsic ion channels
3. Enzymatic receptors
4. Receptors regulating gene expression (Transcription factors)

DRUG-RESPONSE RELATIONSHIP
Two components
1. Dose - plasma concentration relationship
2. Plasma concentration - response relationship

The dose - response relationship curve (DRC) is a rectangular hyperbola

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2005 PHARM ACOLOGY
DRUG POTENCY & DRUG EFFICACY

Fig. Drug A is more potent than drug B, but less efficacious than drug B

Drug potency
• Refers to the amount of drug
• Potency is indicated by the position o f curve on the dose axis
i.e. DRC positioned rightward has lower potency
• Potency is less important than efficacy
• Competitive antagonist act by decreasing the potency o f a drug, such that maximum response
(efficacy) can be still be achieved by increasing dose of agonist - cause rightward shift o f DRC

Drug efficacy
• Refers to max response
• Efficacy is indicated by the upper limit / height of DR C
• Efficacy is more important than potency
• Non-competitive agonist act by decreasing efficacy of a drug, maximum response is suppressed
- flattening of DRC

Therapeutic window phenomenon

For certain drugs optimal therapeutic effect is seen only over a narrow range o f plasm a drug
concentration or drug doses, both below & above the range the effect decreases.
Eg: Clonidine, Glipizide, Imipramine

MEDIAN EFFECTIVE DOSE

EDso - is the dose of drug required to produce 50% o f the maximal response.
It is a measure of the potency o f the drug.

THERAPEUTIC INDEX
The gap between minimal therapeutic effect and max acceptable adverse effects defines the safety
margin or therapeutic index of a drug
Therapeutic index = Median lethal dose / Median effective dose
= LDso / EDso

Drugs with low therapeutic index: - Digoxin, Lithium, insulin, warfarin, phenobarbitone

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COMBINED EFFECT OF DRUGS
Synergism
a) Additive: The effect o f the drugs are in the same direction and simply add up
Effect of drug A + effect of drug B = Effect of drugs A + B
b) Supraadditive (potentiation): The effect o f combination is greater than the individual effects
Effect o f drugs A + B > effect o f drug A + effect of drug B (e g :)

Antagonism: When one drug decreases or inhibits the action of another

I. Competitive antagonist II. Non-competitive antagonist

FACTORS MODIFYING DRUG ACTION

1. Body size 5. Route o f administration

2. Age 6. Environmental conditions
3. Sex 7. Psychological factor
4. Genetics 8. Pathological states (GIT, renal, liver, thyroid diseases, CHF)
5. Other drugs 9. Tolerance (natural, acquired, cross tolerance, tachyphylaxis)

Pharmacogenetic conditions
• G6PD deficiency
• Acetylator polymerization
• Acute intermittent porphyria
• Malignant hyperthermia
1 • Inability to hydroxylate phenytoin
• Resistance to coumarin anticoagulants
• Atypical pseudocholinesterase ^ " , ■
'V \ ^
Antimicrobials needing dose reduction in renal failure
Aminoglycosides Amphotericin B
Cephaloridine Flucytosine
Ethambutol Acyclovir
Vancomycin

ADVERSE DRUG E F F E C T S j

1. Side effects
2. Secondary effects
3. Toxic effects (toxicity, poisoning)
4. Intolerance
5. Idiosyncrasy
6. Drug allergy
7. Photosensitivity
8. Drug dependence (Psychological dependence, Physical dependence, Drug abuse, Drug
Addiction, Drug habituation)
9. Drug withdrawal reactions
10. Teratogenicity
11. Carcinogenicity and Mutagenicity
12. Drug induced diseases (iatrogenic)
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 DIAM S 10
2$I5 PHARMACOLOGY
ll AUTONOMIC NERVOUS SYSTEM ||

Differences between Somatic & Autonomic nervous system

• Organ supplied
• Distal most synapse
• Nerve fibres
Somatic Autonomic (symp & parasym)
Skeletal muscles All other organs
Within CNS Outside CNS (in ganglia)
Myelinated Pregang - myelinated
Postgang - non-myelinated

• Peripheral plexus formation Absent Present

• Efferent transmitter Acetylcholine Acetylcholine, NA, Adr
• Effect o f nerve section on organ Paralysis and atrophy Activity maintained, no atrophy

Differences between Sympathetic & Parasympathetic divisions of autonomic nervous system

Sympathetic Parasympathetic
• Origin Dorso-lumbar (T1 to L2 or L3) Cranio-sacral (III, V II, IX , X ) , S 2 - S 4
• Distribution Wide Limited to head, neck, and trunk
• Ganglia Away from organs On or close to the organ
• Postgang. Fibre Long Short
• Pre:post ganglionic 1:20 to 1:100 1:1 to 1:2 (except in enteric plexuses)
fibre ratio
■ \
• Neurotransmitter NA (Major), Ach (major) Acetylcholine
• Important function Tackling stress and emergency Assimilation o f food, conservation o f energy

Functions of parasympathetic & sympathetic system

ORGANS PARASYMPATHETIC SYMPATHETIC
Eyes Miosis Mydriasis
Heart Bradycardia Tachycardia
Decrease in conduction velocity Increase in conduction velocity
(partial to complete A-V block)
Decrease in contractility Increase in contractility
Blood vessels Dilatation Constriction
Constriction o f coronary arteries Constriction (a l, a2), Dilatation(p2)
Lungs Bronchoconstricition Bronchodilatation
GIT Increases motility Decreases motility
Relaxation of sphincters Contraction of sphincters
Stimulation of secretions o f glands Inhibition o f secretions
Contraction of gall bladder & ducts Relaxation of gall bladder & ducts
Increased insulin secretion Decreased (a2) or Increased ((32)
insulin secretion
Urinary bladder Contraction of Detrusor muscle Relaxation o f detrusor
Relaxation of trigone & sphincter Contraction o f trigone & sphincter

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Glands - Salivary Profuse, watery secretion (Salivation) Thick, viscous secretion
x Sweat Generalized secretion (sweating) Slight, localized secretion
Male sex organs Erection Ejaculation (a l)

ACh ACh

Site o f cholinergic transmission

1. All autonomic ganglia (both parasympathetic & sympathetic)
2. All postganglionic parasympathetic
3. Few postganglionic sympathetic (sweat glands, some blood vessels)
4. Adrenal medulla
5. Skeletal muscles

Sites o f adrenergic transmission

1. All postganglionic sympathetic (except sweat glands, some blood vessels)

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 DIAMS 12
2005 PHARMACOLOGY
CHOLINERGIC D R UG S!

• Cholinoreceptors
Muscarinic receptors
• M l: Nerve endings, Gastric glands, CNS (Antagonist: Pirenzepme)
• M2: Heart
• M3: Visceral smooth muscle, Endothelium, Exocrine glands
i
Nicotinic receptors
• N m: Neuromuscular junction of SKM (Antagonist: d-Tubocurarine)
• N n : Autonomic ganglia (Sym & parasym) (Antagonist: Trimethaphan)

Classification
1. Cholinomimetics
Acetylcholine
Carbachol
Bethanecol
Pilocarpine

2. Anticholinesterases
Reversible Irreversible
Carbamates: Physostigmine Organophosphates: Echothiopate
Neostigmine Parathion, Malathion
Endophronium Dyflos
Acridine : Tacrine Carbamates : Carbaryl, Propoxur

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2005 PHARMACOLOGY
Physostigmine Neostigmine
1. Tertiary amine derivative 1. Quartemary ammonium compound
2. Good oral absorption 2. Poor oral absorption
3. Penetrates cornea 3. Poor penetration o f cornea
4. Crosses BBB, CNS effects present 4. Does not cross BBB, CNS effects absent
5. Prominent effect on autonomic effectors 5. Prominent effect on skeletal muscles
6. Used as miotic (glaucoma) 6. U sed in Myasthenia gravis

USES:
• Glaucoma (Pilocarpine, Physostigmine)
• Myasthenia gravis (Neostigmine)
• Post-op decurarization (Neostigmine)
• Cobra bite (Neostigmine + Atropine to prevent respiratory paralysis)
• Alzheimer’s disease (Tacrine, Donepezil)
• Diagnosis o f M yasthenia gravis (Ameliorative test by endrophonium)
• Belladonna poisoning (Physostigmine)

Anticholinesterase poisoning
S - Salivation, Sweating, Secretions
L - Lacrimation (PUPILS ARE CONSTRICTED)
U - Urination
D - Diarrhea
p th e r symptoms: Fall in BP, Tachycardia, cardiac arrhythmia, respiratory failure.

T/t: Antidote: a) Anticholinergic: ATROPINE

b) Cholinesterase reactivators^))RALIDOXIM E (2 - PAM)
(Note: Pralidoxime is not effective in carbamate poisoning)

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 DIAMS 14
2005 PHARMACOLOGY
ANTICHOLINERGIC DRUGS |

1. N atural A lkaloids: Atropine, Hyoscine (Scopolamine)

2. Sem isynthetic: Homatropine, Ipratropium bromide
3. Synthetic:
• M ydriatics: Cyclopentolate, Tropicamide
• Antisecretory-antispasmodics: Glycopyrolate, Pirenzepine, Dicyclomine, Oxybutynin
• Antiparkinsonian. Trihexyphenidyl (Benzhexol), Benztropine

Atropine
• Topical use for mydriasis (Atropine 1% oint - mydriatic o f choice in children < 5 yrs.)
• Topical use for cycloplegia in iritis, iridocyclitis, choroiditis, keratitis, comeal ulcer.
• Bradycardia & AV block in MI, digitalis toxicity.
• Specific antidote for antiChE poisoning

C/I: Narrow iridocorneal angle - may precipitate acute congestive glaucoma.

Benign prostatic hypertrophy (BPH) - Urinary retention can occur.

Hyoscine
• Prevention & treatment o f motion sickness (oral, transdermal)

Ipratropium brom ide

• Bronchodilator o f choice in COPD (more effective than [32 agonists)
• ADR: Dryness o f mouth, Scratching o f trachea, bad taste

Tropicam ide '

• Quickest & briefest mydriatic for fundoscopy

Glycopyrolate
• Lacks CNS effects
• Used for preanaesthetic medication

Pirenzepine
• Selective M l muscarinic blocker.
• Inhibits gastric secretion, hence used in peptic ulcer.
a

Dicyclomine
• Antispasmodic, used in intestinal, renal colic, abdominal cramps.

Oxybutynin
• Vesicoselective action, Hence used for detrusor instability (urge incontinence, involuntary
voiding)

Benzhexol (T rihexyphenidyl)
• DOC for drug induced Parkinsonism & treating extrap yramidal symptoms d/t antipsycho tics.

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 DIAMS 15
2005 PHARMACOLOGY
ADRENERGIC DRUGS ||

Endogenous catecholemines: Epinephrine, Norepinephrine & Dopamine.

Release of NA by displacement: Tyramine (indirectly acting sympathomimetic)

Inhibition of axonal uptake o f CA: Coc'aine
Inhibition of granular uptake o f CA: Reserpinex ^
Displacement of granular NA: Guanethidine
MAO inhibition: Nialamide
COMT inhibition: Tolcapone, Entacapone.
Receptors: (see below)

Adrenergic receptors

a1 a2
Location Postjunctional on effector organs Prejunctional on nerve endings,
9 Postjunctional in brain, pancreas
Function • Constriction o f blood vessels— in BP l secretion o f NA from nerve endings
• Eye - Mydriasis, l aqueous secretion Inhibition o f insulin release
• Intestinal relaxation, sphincters contr-n
• Bladder trigone - contraction
• Uterus —contraction
• Liver —■>glycogenolysis
• M ale sex organs —» ejaculation
Selective agonist Phenylephrine Clonidine, a - Methyldopa
Selectiveantagonist Prazosin Yohim bine
Effector pathway IP 3/D A G t cAMP T, K+channel t, IP3/DAG |

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 DIAMS 16
2005 PHARMACOLOGY

PI P2 P3
Location ■ Heart Bronchi, blood vessels, Adipose
■ JG cells in kidney g.i.t, uterus, urinary tract, eye tissue
Function • H eart - j in rate, force of • Dilatation o f blood vessels-], BP Fat
contraction • No effect on iris, t aqueous lipolysis
• Renin release from secretion
kidney • Intestinal relaxation
• Detrusor - relaxation
• Uterus relaxation
• Increase release o f insulin
• Liver —» Hyperglycemia
Muscle —►Hyperlactacidemia
Selective agonist Dobutamine Salbutamol, Terbutaline
Selective antagonist M etoprolol, Atenolol Butoxamine

Classification
Pressor agents: Noradrenaline, Dopamine, Methoxamine, Ephedrine, Mephentermine
Cardiac stim ulants: Adrenaline, Dobutamine, Isoprenaline
'Bronchodilators: Adrenaline, Salbutamol, Salmeterol, terbutaline
Nasal decongestants: Phenylephrine, Pseudoephedrine, Phenylpropalamine
CNS stimulants: Amphetamine
Anorectics: Fenfluramine, Sibutramine
Uterine relaxant: Ritordine, Isoxsuprine, Salbutamol, Terbi^ajine^

ADRENALINE, N O R A D R EN A L IN E, ISOPRENALINE

Adr: a l + a2 + pi + P2 & weak P3 action

NA: a l + a2 + pi + P3 but no p2 action
Iso: pi + p2 + P3 but no a action

A dr NA
1. Heart rate t i

2. BP - Systolic tt TT
Diastolic u TT -
Mean t TT
Pulse pressure t N

3. Cardiac output TT —

USES: Acute hypersentivity reactions (Type I) - Anaphylaxis

Along with LA to prolong their action & decrease their toxicity
Cardiac arrest (intracardiac)
As a local hem ostatic on bleeding surface

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2005 PH ARM ACOLOGY
Vasomotor reversal phenomenon o f Dale is seen with Adrenaline, a fall in BP when given with a
blocker (d/t block of a receptors)

DOPAMINE
• Dopamine (D l, D2) & adrenergic a and pi agonist (But not p2 agonist)
• Increases BP, Dilatation o f renal and mesenteric vessels.
• Used in Cardiogenic shock, septic shock, Shock a/w oliguria.

DOBUTAMINE
• Selective pi agonist (Not a D l or D2 agonist)
• Increases CO without change in HR & BP.
• Used in Cardiogenic shock, CHF, Acute MI with CHF

PHENYLEPHRINE
• Selective a l agonist
• Mydriatic WITHOUT cycloplegia.

SELECTIVE P2 AGONISTS
• Salbutamol, Salmeterol, Terbutaline, Formoterol, Ritordine, Orciprenaline, Bitolterol
• Actions: Bronchodilatation, Vasodilatation, Uterine relaxation
• Adv: Tremors, Tachycardia, Tolerance (3’T ’)
Hypokalemia, Hyperglycemia (2’H ’)
* • Uses: Bronchial asthma & COPD
Premature labour (Ritordine)
Hyperkalemic familial periodic paralysis
V v '**■' •
AMPHETAMINE
• Drug included in the “dope test” for athletes
• Uses: Attention deficit hyperactivity disorder in children (DOC)
Narcolepsy (Other drugs —Imipramine, Modanofil)
• Adv: Tolerance - psychic & physical dependence, Psychosis

Other drugs
Fenoldopam
• Peripheral vasodilator, D l agonist.
• Used in hypertensive emergency as an alternative to Sodium nitroprusside.
Xamoterol, Prenalterol: Selective pi agonists
Dopexamine: Related to dopamine, Positive inotropic action, produces renal, pulmonary vasodilation

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 DIAMS 18
2005 PH ARM ACO LO G Y

1. Non-selective a blockers
• Non-competitive: Phenoxybenzamine
• Competitive: Phentolamine, Tolazoline
Ergot alkaloids: Ergotamine.
2. Selective a blockers
• a l blockers-. Prazosin, Terazosin, Alfazosin, Tamusulosin, U rapidil
• a2 blockers: Yohimbine.

Phenoxybenzamine
• Used for preoperative, intraoperative & postoperative management o f Pheochromocytoma.
Also for chronic therapy o f inoperable tumours.

Phentolamine
• Used for diagnosis & intraoperative management (for control of hypertension) o f
pheochromocytoma
• Used for control o f hypertension due to clonidine withdrawal, cheese reaction.

Ergotamine
• Partial agonist & antagonist at a - adrenergic and at 5-HT1 and 5-HT2 receptors
• Causes sustained vasoconstriction
• Used in Migraine (moderate & severe form) to relibVb;4ttac!ks.
• Adv: Gangrene of extremities. v X

Prazosin
• Selective a l blocker
• Uses: Antihypertensive
Benign prostatic hypertrophy
PVD, Raynauds’s phenom enon
• Adv: Postural hypotension in the beginning “first dose effect” .

Terazosin, Alfuzosin, Doxazosin

• Preferred a 1 blockers in BPH

Tamusulosin
• Selective a ia blocker (a l A receptors are located in prostate, a ib in vascular smooth muscle)
• Used in BPH - Improves urinary symptoms without change in BP or HR.
• Adv: Retrograde ejaculation

Urapidil
• Selective a l blocker, used in hypertensive emergency.

O ther drugs
Sildenafil: Selective PDE-5 inhibitor. U sed for treatment of erectile dysfunction.
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 DIAMS 19
2005 PHARM ACOLOGY
p - BLOCKERS 1|

Non- selective (pi and p2)

a. Without intrinsic sympathomimmetic activity: Propranolol, Nadolol, Timolol, Sotalol
b. With intrinsic sympathomimmetic activity. Pindolol, Oxprenolol
c. With additional a blocking property: Labetelol, Carvedilol

Selective pi blockers (cardioselective)

• Metoprolol, Atenolol, Acebutolol, Bisoprolol, Esmolol, Betaxolol, Celiprolol.

Selective p2 blocker
• Butoxamine.

Propranolol
High first pass metabolism
Metabolism of Ppnl is dependent on hepatic blood flow. Itself decreases hepatic blood flow.
Max membrane stabilizing activity, local anaesthetic property.

Adv: Accentuates myocardial infarction (worsen CHF)

Impaired carbohydrate tolerance (worsen DM)
Altered plasma lipid profile.
Worsening o f PVD (p2 block - vasoconstriction)
Prinzmetal’s (Variant’s) angina precipitation.
: Bradycardia & rebound hypotension.
AV block ( | AV conduction)
Worsen Bronchial asthma (p2 block, - bronchoconstriction)
Vv
Uses: Angina pectoris Sinus tachycardia, Digitalis induced tachyarryhthmia
Hypertension Hypertrophic Cardiomyopathy (D O C)
Migraine prophylaxis Pheochromocytoma
Thyrotoxicosis Congenital prolonged QT
Post MI arrhythmia Chronic variceal bleeding.
Essential tremors (DOC)

C /I: AV block
Bronchial asthma (BA) (PNEUMONIC “ABCD- 2P”)
CCF
Diabetes mellitus (DM)
PVD
Prinzmetal’s angina

Nadolol: Longest acting, Lipid insoluble, Excretion by kidneys, do not cross BBB.
Sotalol: P - blocker with additional K+ channel blocking & class III antiarrhythmic property.
Lipid insoluble, Excretion by kidneys, do not cross BBB
Timolol: Topically used in wide angle glaucoma.
Pindolol, Oxyprenolol: Does not cause bradycardia

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 DIAMS
2005 PHARM ACOLOGY
Cardioselective B1 blockers
Metoprolol: Cardioselective p i blocker, can be used in BA, DM and PVD.
Atenolol: Lipid insoluble, Excretion by kidneys, do not cross BBB.
Esmolol: Ultrashort acting, DOC for Emergency control o f ventricular rate in AF / AF1, anaesthesia.
Acebutolol: Intrinsic sympathomimetic activity (no bradycardia), Membrane stabilizing activity.
Betaxolol: Selective pi blocker used in glaucoma
Celiprolol: p i antagonist with partial p2 agonistic activity.

Some imp points

Shortest acting P blocker - Esmolol
Longest acting p blocker - Nadolol
p blockers C/I in renal failure - Atenolol, Nadolol, Sotalol (ANS)
p blockers which are lipid insoluble - Atenolol, Nadolol, Sotalol (ANS)
p blockers which do not cause bradycardia - Pindolol, Oxyprenolol, Acebutolol (POA)
p blockers which have membrane stabilizing activity - Ppnl, Oxyprenolol, Acebutolol
p blocker which have maximum membrane stabilizing activity - Ppnl.
p blocker with marked class III antiarrhythmic property - Sotalol

\A v

24 HRS HELPLINE: 9891436206/9891334352

 DIAMS 21
PHARMACOLOGY

PROSTAGLANDINS & LEUKOTRIENES

MEMBRANE LIPIDS

PHOSPH OLIPASE A2
ZILEUTC
L.- rf r
ARACH1DONIC ACID ^ NSAIDS
/
/
y
LIPOXYGENASE CYCLOOXYGENASE
(COX I, COX II)

Leukotrienes
LTA4

Thromboxane A2 Prostacyclins Prostaglandins

LTB4 LTC4 (TXA2) (PGI2) (PGE2, PGD2, PGF2a)
LTD4
LTE4
t ZAF1RLUKAST
RECEPTORS<■ MONTELUKAST

Thromboxane A i (TXA2) Prostaglandin F2a (PGF2a)

Produced by platelets Vasodilatation
Vasoconstriction Oxitoxic (contracts uterus), abortificient
j Platelet aggregation V Bronchoconstricti on
vY v '"VA
*• v\'\\
Prostacyclin (PGI2)
Produced by endothelium Prostaglandin E2 (PGE2)
Vasodilatation Vasodilatation
i Platelet aggregation (antiaggregatory) Oxitoxic (contracts uterus), abortificient
Bronchodilatation Bronchodilatation
Maintains patency o f ductus arteriosus Maintains patency of ductus arteriosus
i gastric acid secretion, f mucous production j gastric acid secretion, f mucous
production

Leukotrienes
LTB4 - produced by neutrophils, LTC4, LTD4 - produced by macrophages
Most potent bronchoconstrictors

USES:
• Abortion in early and mid trimester pregnancy, in missed abortion (PGE2, PGF2a)
• Induction o f labour (PGE 2, PGF201)
• Cervical priming (PGE2)
• Postpartum haemorrhage (PGF2a - Carboprost)
• Peptic ulcer & prevention of NSAIDs induced gastric injury (PGE2 - Misoprostol, PGI2)
• Glaucoma (PGF2a - Latanoprost)
To maintain patency o f ductus arteriosus in neonates with congenital defects (PGEi-Alprostadil)
24 HRS HELPLINE: 9891436206/9891334352
 DIAMS 22
2005 PHARMACOLOGY

|j NONSTEROIDAL ANTIINFLAMMATORY DRUGS (NSAIDsTTI

Non-selective COX inhibitors

Salicylates: Aspirin, Sulfasalazine
Paracetamol (NO anti-inflammatory action)
Indomethacin
Difclofenac
Ibuprofen, Naproxen
Ketorolac
Piroxicam, Tenoxicam

Preferential COX-2 inhibitors

Nabumetone, Nimesulide, Meloxicam

Selective COX-2 inhibitors

Celecoxib, Rofecoxib, Valdecoxib*•

CO X exists in 2 forms:
1) COX-1 is constitutive enzyme expressed in most tissues and involved in physiological functions.
2) COX-2 is induced in inflammatory cell and produces prostanoid mediators of inflammation.

Non-selective COX inhibitors

Actions'. Anti-inflammatory,.Antipyretic, Analgesic, AntiptldJtg^t^tion

USES:
• Acute rheumatic fever (Aspirin)
• Prophylaxis in Post MI & Post stroke, TIA (Aspirin - antiplatelet action)

Patent ductus arteriosus

Bartter’s syndrome
Ankylosing spondylitis > (DOC is Indomethacin)
Acute gouty attack
J

Postoperative pain relief (Transdermal ketorolac)

Ulcerative colitis (Sulfasalazine)
Rheumatoid arthritis, Osteoarthritis

ADR:
Nausea, vomiting, dyspepsia, peptic ulceration (C/I in peptic ulcer)
Analgesic nephropathy - pappilaiy necrosis o f kidney, after prolonged use
Idiosyncrasy - rash, fixed drug eruption, asthma, anaphylactoid reaction
Salicylism - dizziness, vertigo, tinnitus, dimness o f vision, mental confusion
Reye’s syndrome - hepatic encephalopathy in children < 13 yrs, with viral infections (varicella,
influenza)

24 HRS HELPLINE: 9891436206/9891334352

 DIAMS
2005 PHARMACOLOGY
• Premature closure of ductus arteriosus, LBW, pulmonary hypertension in pregnancy (C/I)
• Hemolysis in G6PD deficiency
• Blood dyscrasias (aplastic anemia) - Indomethacin, phenylbutazone, diclofenac
• Acute salicylate poisoning (Dehydration, hyperpyrexia, acidotic breathing, convulsions)
T/t: Symptomatic & supportive (Gastric lavage, Forced alkaline diuresis, Hemodialysis)
• Acute paracetam ol poisoning (Centrilobular hepatic necrosis, renal tubular necrosis,
hypoglycemia)
T/t: Specific antidote - N-acetylcysteine

Selective COX-2 inhibitors

Celecoxib, Rofecoxib, Valdecoxib
• Minimal ulcerogenic potential
• Used in acute musculoskeletal pain, osteoarthritis, RA

24 HRS HELPLINE: 9891436206/9891334352

 DIAMS 24
2005 PHARMACOLOGY
DRUGS USED IN GOUT

Acute gout:
• NSAIDs: Indomethacin (DOC), Naproxen, Piroxicam (Note: Aspirin is contraindicated)
• Colchicine
• Corticosteroids

Chronic gout:
• Uric acid synthesis inhibitor: Allopurinol
• Uricosuric drugs: Probenicid, Sulphinpyrazone

Colchicine
MOA: Inhibitor o f microtubule assembly (mitotic spindle formation), causes metaphasic arrest.
Inhibits granulocyte migration & phagocytosis
ADV: Diarrhea (M/C)
Myopathy, alopecia,
Agranulocytosis, aplastic anemia
Kidney damage, CNS depression

Allopurinol

Uric acid

MOA: Inhibitor & substrate for xanthine oxidase

ADV: Muscle pain, malaise, rash
Increases levels of 6-Mercaptopurine, Azathioprine
USES: Chronic gout
Secondary hyperuricemia (d/t cancer chemotherapy, radiation, drug induced)
Visceral leishmaniasis (Kala azar), as an adjuvant to Sod. stibogluconate

Probenicid
MOA: Competitively inhibits active transport o f organic acids in renal tubules (bidirectional)
Penicillin is mainly excreted, so probenicid inhibits its secretion, hence |e s its levels
Uric acid is mainly reabsorbed, so probenicid promotes its excretion and J,es its levels
Uses: Chronic gout, secondary hyperuricemia
Also used to prolong the action o f penicillin / ampicillin eg: in gonorrhoea, SABE

Sulphinpyrazone
Inhibits uric acid reabsorption. Also inhibits platelet aggregation
ADV: Gastric irritation - C/I in peptic ulcer

24 HRS HELPLINE: 9891436206/9891334352

 DIAMS 25
2005 PHARMACOLOGY

|| DRUGS FOR RHEUMATOID ARTHRITIS

Rheumatoid arthritis: is an autoimmune disease in which there is joint inflammation, synovial

proliferation and destruction o f articular cartilage.

1. NSAIDs
2. Disease modifying anti-rheumatic drugs (DMARDs)
• Gold salts (Auranofm, Sod. aurothiomalate)
• Penicillamine
• Chloroquine
• Sulfasalazine
• TNF Inhibitors (Infliximab, Etanercept)
• Leflunomide
• Immunosuppressants (Methotrexate, Azathioprine, Cyclosporine)
• Corticosteroids

Note: First line treatment - NSAIDs

DMARDs o f choice - Methotrexate

NSAIDs - afford symptomatic relief (pain, swelling, morning stiffness instability), but do not arrest
the disease process.
DMARDs - have no inflammatory or analgesic action, but suppress the rheumatoid process and bring
i about a remission.

V\t; s\N\

24 HRS HELPLINE: 9891436206/9891334352

 DIAMS 26
2005 PHARMACOLOGY

l.Bonchodilators
• p2 agonists (Salbutamol, Salmeterol, Terbutaline, etc)
• Methylxanthines (Theophylline, Aminophylline)
\
• Anticholinergics (Atropine, Ipratropium bromide)

2.Leukotriene A ntagonists
• Lipooxygenase (LOX) inhibitor: Zileuton
• Leukotriene receptor antagonists: Montelukast, Zafirlukast.

3.Mast Cell Stabilizers:

• Sodium cromoglycate, Nedocromil, Ketotifen

4.Corticosteriods
• Systemic: Hydrocortisone, Prednisolone
• Inhalational: Beclomethasone, Budesonide, Triamcinolone, Flunisolide *•

P2 agonists
• Salbutamol, Terbutaline - Short acting (< 6 hrs)
• Salmetrol, Formoterol - Long acting ( 6 - 1 2 hrs)
• Adv: Tremors, Tachycardia, Tolerance (3’T ’)
Hypokalemia, Hyperglycemia (2’H ’)

24 HRS HELPLINE: 9891436206/9891334352

 DIAMS 27
2005 PHARMACOLOGY
Methylxanthines
Theophylline:
• Zero order kinetics
• Low therapeutic index
• MOA: 1) Increase in cAMP by inhibiting PDE III
2) Blokade o f adenosine receptors
3) Release o f Ca+ from SR in SKM & CM. ( | diaphragmatic contractibility)
• Adv: Insomnia, tremors, palpitation, hypotension, convulsions
® Factors which need dose reduction:
o Age >60 yrs
o CHF, Pneumonia, Liver failure
o Drugs fing toxicity - Erythromycin, Ciprofloxacin, Cimetidine, OCP, Allopurinol
• Uses: BA, COPD, Apnoea in premature infants

Anticholinergics
Ipratropium bromide
• Bronchodilator of choice in COPD (more effective than (32 agonists)
• ADR: Dryness o f mouth, Scratching of trachea, bad taste

Mast cell stabilizers

MOA: stabilizes mast cell membrane and inhibits release o f mediators.
Used primarily as prophylactic for
^ • Allergic bronchial asthma
' • Allergic rhinitis, Spring catarrh, Aphthous stomatitis, food allergy

Corticosteroids v x*
^ V‘' V , A
• Inhalational steroids —Mainly for prophylaxis (NO role during an acute attack)
Adv: Oropharyngeal candidiasis - M/C
• Systemic steroids
Used in Status asthmaticus, severe chronic asthma

Leukotriene inhibitors
• DOC for aspirin induced asthma
• Adr: Churg strauss syndrome

CHOICE OF TREATMENT
1. Mild episodic asthma (symptoms less than once daily, normal in between attacks)
• Inhaled short acting (32 agonist at onset of each episode. N o prophylaxis needed

2. Mild chronic asthma with occasional episodes (symptoms once daily or so)
• Regular inhaled low dose steroid or sodium cromoglycate
• Episodic t/t with inhaled short acting (32 agonist

3. Moderate asthma with frequent episodes (> 1 per day)

• Regular inhaled high dose steroid + long acting (32 agonist (salmetrol)
• Episodic t/t with inhaled short acting (32 agonist

24 HRS HELPLINE: 9891436206/9891334352

 DIAMS 28
2005 PHARM ACOLOGY
4. Severe asthma (continuous symptoms, frequent episodes every day / hosptilisation)
• Regular inhaled high dose steroid + long acting (32 agonist twice daily ± methylxanthine
/oral (32 agonist/ inhaled ipratropium bromide
• Episodic t/t w ith inhaled short acting p2 agonist
• Uncontrolled or needing frequent emergency care - A dd oral steroids to the regime

5. Status asthmaticus
• Systemic corticosteroids: Hydrocortisone
• Inhaled p2 agonists - salbutamol, terbutaline
• Intermittent humidified oxygen inhalation

New drugs
Piclamilast - Selective PDE III inhibitor, have both bronchodilator & anti-inflammatory potential

24 HRS HELPLINE: 989143620 3/9891334352

 DIAMS 29
2005 PHARM ACOLO

INSULIN & ORAL HYPOGLYCAEMIC AGENTS

A. ORAL HYPOGLYCAEMIC AGENTS

• Sulfonylureas
o First generation (less potent): Tolbutamide, Chlorpropamide
o Second generation (more potent): Glibenclamide, Glipizide, Gliclazide, Glimepiride
• Biguanides: Phenformin, M etformin
• Meglitinide analogues: Repaglinide, Nateglinide
• Thiazolidincdiones: Rosiglitazone, Proglitazone
• a - glucosidase inhibitors: Acarbose, Miglitol

B. INSULIN *•

Sulfonylureas
MOA: 1) f release o f endogeneous insulin from islets (Blocking K+ channels - Depolarisation o f (3
cell - Release of insulin)
2) | no: of insulin receptors in insulin sensitive tissues.
3) | the sensitivity of peripheral tissues to insulin.

Tobutamide: low potency, shortest acting, less prone to hypoglycaemia

Chlorpropamide:
F • Longest acting
' • More prone to prolonged hypoglycaemia
• Dilutional hyponatremia - ADH like action
• Disulfiram like reaction with alch\xho|\v
• Cholestatic jaundice
Glipizide: Fastest acting
Gliclazide: has antiplatelet action.
Glimepiride: Stronger extrapancreatic action, less hyperinsulinemia

USES: Diabetes mellitus (NIDDM Type II)

Diabetes insipidus (Chlorpropamide)

Biguanides
MOA: Supress hepatic gluconeogenesis
Inhibits intestinal absorption o f glucose
Promotes peripheral glucose utilization
Enhance binding o f insulin to its receptors
(Note: DO NOT cause release o f insulin)
DO NOT cause Hypoglycaemia)

Adv: GI disturbance
Lactic acidosis - more common with Phenformin
Weight loss
Uses: Obese, diabetic
Secondary failure, added to sulfonylurea.

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 DIAMS 30
2005 PHARM ACOLOGY
Meglitinide analogues
Repaglinide, Nateglinide
MOA: same as sulfonylureas
Used to reduce Postprandial hyperglycemia in NIDDM type II.

Thiazolidinedions
Rosiglitazone, Proglitazone
Selective agonists for nuclear perioxisom e proliferators activated receptor-gamma (PPAG)
Sensitizes peripheral tissues to insulin
Used in type II DM
Adv: Liver toxicity.

a - glucosidase inhibitors
Acarbose, Miglitol
MOA: jes intestinal absorption o f starch & polysaccharides by inhibiting the action o f intestinal brush
border a - glucosidase.
Decreases postprandial hyperglycemia
Adv: Flatulence.

INSULIN

Preparation Onset Duration

I. Ultra short acting
• Insulin lispro 15 min - 20 min 3 - 4 hrs
• Insulin Aspart 15 m in - 2 0 m in 3 - 4 hrs
II. Short acting
• Regular (soluble) insulin f 30 min' - 1 hr 6 - 8 hrs
• Semilente (Insulin zinc suspension) 1 hr 12 - 16 hrs
III. Intemediate acting
• NPH (Isophane insulin) 1 - 2 hrs 20 - 24 hrs
• Lente insulin (Ultra:semi:: 7:3)
IV. Long acting
• Ultra lente insulin 4 - 6 hrs 2 4 - 3 6 hrs
• Protamine insulin

All the insulin preparations are given subcutaneously. Only REGULAR INSULJN can be given I.V.

Uses: IDDM type I, Juvenile onset diabetes

NIDDM type II, not responding to OHA
Diabetes in pregnancy (DOC)
Diabetic ketoacidosis (Diabetic coma), Hyperosmolar non-ketotic coma
Adv: Hypoglycemia
Lipodystrophy
Allergy
Insulin resistance

Drugs causing hyperglycemia: Steroids, Glucagon, Somatostain, Diazoxide, OCP, Thiazides,

Phenytoin, Streptozocin, Pentamidine
24 HRS HELPLINE: 9891436206/9891334352
 DIAMS 31
2005 PHARMACOLOGY

|l THYROID INHIBITORS |
A. Drugs that inhibit synthesis (Antithyroid drugs)
Propylthiouracil, methimazole, carbimazole
B. Drugs that inhibit iodide trapping (Ionic inhibitors)
Thiocynates (-SCN), Perchlorates (-C104), Nitrates (-NO 3)
C. Drugs that inhibit hormone release
Iodine, Iodide of Na & K, p blokers
D. Drugs that destroy thyroid tissue
. Radioactive iodine I 13111251 123
E. Others
Lithium, Amiodarone, Goitrogens (cabbage, turnip, mustard)

Antithyroid Drugs
.MOA: inhibit the enzyme thyroid peroxidase (TPO), thereby
■ Inhibit oxidation o f iodide
■ Inhibit iodization of tyrosine residues
■ Inhibit coupling o f MIT, DIT

Propylthiouracil Carbimazole / Methimazole

■ High protein binding Less protein binding
■ Less transfer across placenta and in milk More transfer
-i: (DOC for hyperthyroidism in PREGNANCY)
■ Inhibits peripheral conversion of T4 —>T3 Does not inhibit conversion
ADR:
o Hypothyroidism
o Skin rashes
o Agranulocytosis
USES: Definitive therapy in Grave’s disease, less than 40 yrs
Preoperatively, to bring euthyroid state
Along with I 123 therapy for initial control o f hyperthyroidism

Iodine & Iodides

MOA: inhibits hormone release ‘thyroid constipation’
Uses: Preoperative preparation for thyroidectomy (to decrease vascularity of the gland)
Thyroid storm, along with antithyroid drugs & propronalol
Prophylaxis of endemic goitre '

Radioiodine
Ii23:- Emits both x-rays (diagnostic) and p particles (therapeutic)
Indications: Diffuse toxic goiter (Grave’s disease), or Toxic nodular goitre in patients, above 40 years
Recurrent thyrotoxicosis after surgery
Poor risk patients.
❖ Absolutely contraindicated in children & pregnant

P B lockers
MOA: Inhibit release of hormone, Also decrease sympathetic over activity
Uses: Thyrotoxic crisis (Thyroid storm), Pre-operative preparation
24 HRS HELPLINE: 9891436206/9891334352
 __

eS

Fig: A= Drugs that inhibit synthesis, B= Drugs that inhibit iodide trapping, C= Drugs that inhibit hormone release
 DIAM S 33
2005 PHARMACOLOGY
ll CORTICOSTEROIDS [

Agent Gluco M ineralo

Q Short acting 1. Hydrocortisone (Cortisol) 1 1
O (t'/2 < 12 hrs) 2. Cortisone 0.8 0.8
O Intermediate 3. Prednisolone 4 0.8
Pi Acting 4. Methylprednisolone 5 0.5
O (t'/2 12 - 36 hrs) 5. Traimcinolone 5 0
o
u Long acting 6. Paramethasone 10 0
p (t‘/ 2 >36 hrs) 7. Dexamethasone 25 0
p
o 8. Betamethasone 25 0

d o 9. Aldosterone 0.3 3000

10. Fludrocortisone 10 150
•z, Pi 11. Deoxyxorticosterone acetate (DOCA) 0 100
5 O
S o

Note:
“ Highest glucocorticoid activity - Betamethasone, Dexamethasone
■ Highest mineralocorticoid activity -A ld o stero n e
■ Steroids with zero glucocorticoid activity - DOCA
■ Steroids with zero minerlocorticoid activity - Betamethasone, Dexamethasone,Paramethasone,
1 Triamcinolone
■ Glucocorticoid with highest mineralocorticoid activity - Hydrocortisone

Inhalational steroids: Beclomethasone, Budenoside, Triamcinolone, Flunisolide

Uses:
A. Replacement therapy
• Acute adrenal insufficiency
• Chronic adrenal insufficiency (Addison’s disease)
• Congenital adrenal hyperplasia (Adrenogenital syndrome)
B. Pharmacotherapy
• Arthritis (RA, RF, Osteoarthritis, Gout)
• Collagen vascular diseases (SLE, PAN, Dermatomyositis)
• Severe allergic reactions
• Autoimmune diseases
• Bronchial asthma
• Prevention o f RDS in premature infants
• Inflammatory ocular diseases
• Inflammatory bowel diseases (Crohn’s disease, UC, Celiac disease)
• Cerebral edema
• Malignancies (lymphomas, acute leukemias)
• Organ transplantation

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 DIAM S 34
2005 PHARMACOLOGY
A dverse Effects:
• Salt & water retention, hypokalemia
• Cushing habitus
• Fragile skin, purple striae
• Hyperglycemia
• Osteoporosis
k • Myopathy proximal (shoulder, arm, pelvis, thigh)
• Susceptibility to infection
• Delayed healing
• Peptic ulceration
• Cataract posterior subscapular (systemic steroids)
• Glaucoma (Topical steroids)
• Growth retardation
• Psychiatric disturbances
• Supression of hypothalamo-pituitary adrenal (HPA) axis

C ontraindications
• Peptic ulcer
• Diabetes mellitus
• Hypertension
• Tuberculosis
• Renal failure
• Congestive cardiac failure
• Osteoporosis
• Herpes simplex keratitis
• Psychosis
• Epilepsy

In h ib ito rs of Steroids synthesis

o Metyrapone - Inhibits 11-(3 hydroxylase in adrenal cortex.
Used in cushing’s syndrome or adrenal tumours
o Ketoconazole - Inhibits Cytochrome P450 enzyme
o Mitotane - used in adrenal Cancer
oTrilostante

In h ib ito rs of Steroids action

o Spironolactone & eplerenone (Aldosterone antagonist)
o Mifepristone (Progesterone & glucocorticoid antagonist)

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 DIAM S 35
2005 PHARMACOLOGY

([s e d a t i v e s - h y p n o t i c s !
• Barbiturates
Long acting: Phenobarbitone
Short acting: Secobarbitone
Ultrashort acting: Thiopentone

• Benzodiazepines
Diazepam, Lorezepam, Alprazolam, Midazolam, Chlordiazepoxide, Clonazepam

♦> Newer nonbenzodiazepine hypnotics

Zolpidem. Zolpiclone

BARBITURATES H
• MOA: GABA-mimetic action
• Dose dependent actions: Sedation —» Sleep —»■Anaesthesia —» Coma
• Redistribution —>Highly lipid soluble barbiturates (thiopentone) is distributed into the fat o f body,
hence its action is dimished (ultrashort action)
• A D V : Sedation (M/C), Hangover
Precipitation of porphyria
Hypersentivity: rashes
Enzyme inducers
^ Megaloblastic anemia
’ Osteomalacia
Tolerance, dependence, drug abuse, drug automation
Hyperactivity in children, meht^lxopfusion in older
Behavior abnormalities, impaired intellect

• Poisoning: No antidote, Gastric lavage, forced alkaline diuresis, hemodialysis

•- USES:
o Anticonvulsant (phenobarbitone)
o Anaesthesia (Thiopentone)
o T/t o f kemicterus & hyperbilirubinemia in new born (phenobarbitone)

BENZODIAZEPINES ||
MOA: GABA facilitatory action (do not open Cl- channels, but j frequency o f Cl" channel opening)
B

ADR: Hangover, disorientation, paradoxical agitation & aggression, withdrawal symptoms.

USES:
• Anaesthesia (Midazolam)
• Anticonvulsant - in status epilepticus, febrile convulsions (Diazepam, Lorezepam)
• Anxiolytic (Alprazolam)
• Skeletal muscle relaxation (Diazepam)
• Alchohol withdrawal (Chlordiazepoxide)

Flumazenil: Competitive antagonist of BZD - Specific antidote for BZD overdosage

P carboline: Inverse agonist at BZD site.

24 HRS HELPLINE: 9891436206/9891334352
 DIAM S 36
2005 PHARMACOLOGY

ANTIEPILEPTIC DRUGS
Generalised seizures
Tonic clonic seizures (Grand mal) VALPROIC ACID / PHENYTOIN
Myoclonic seizures VALPROIC ACID
Atonic seizures VALPROIC ACID
Absence seizures (Petit mal) ETHOSUXIMIDE

Partial seizures
Simple partial - CARBAMAZEPINE
Complex partial (Psychomotor epilepsy) - CARBAMAZEPINE

Status epilepticus DIAZEPAM / LOREZEPAM

Epilepsy in Pregnancy PHENOBARBITONE
Febrile seizures RECTAL DIAZEPAM

MOA:
1. Na+ channel inactivation: Phenytoin, Carbamazepine, Valproate
2. Facilitation of GABA mediated Cl- channel opening: Barbiturates, Benzodiazepines, Valproate
3. Inhibition o f £T ’ type Ca++ current: Ethosuximide, Valproate

PHENYTOIN
Pseudozero order kinetics, enzyme inducer, antiarrythmic
ADR: Hyperplasia o f gums
Hyperglycemia ^ , (PNEUMONIC: 6 ’H ’)
Hirsutism \
Hypoclacemia (Osteomalacia)
Hydantoin syndrome (Microcephaly, cleft lip, cleft palate)
Hypersensitivity (DLE, rash)
Pseudolymphoma
Cerebellar symptoms (ataxia, nystagmus)
Megaloblastic anemia, Jaundice

CARBAMAZEPINE
ADR: Neurotoxicity
Hypersensitivity reactions
Lupus like syndrome
Agranulocytosis, leucopenia (rare)
ADH like action (Water retention and hyponatremia)
DOC for PARTIAL SEIZURES and TRIGEMINAL NEURALGIA.
Also used in Maniac depressive illness (alternative to Lithium)

VALPROIC ACID
ADR: Alopecia, curling o f hair,
Neural tube defects - C/I in pregnancy
Hepatitis (avoid in children < 3 yrs)

24 HRS HELPLINE: 9891436206/9891334352

 DIAMS 37
2005 PHARMACOLOGY
OTHER DRUGS
GABA agonist: Gabapentin.
GABA transaminase inhibitor: Vigabatrin
GABA reuptake inhibitor: Tiagabine
Miscelleneous: Lamotrigine, Topiramate, Levetiracetam

ANTIPARKINSONISM DRUGS

Triad of Parkinsonism: Rigidity, Hypokinesia, Tremors (resting)

1. Drugs affecting brain dopaminergic system

a. Dopamine Agonists: LEVODOPA, BROMOCRIPTINE, PERGOLIDE, ROPINIROLE
b. Peripheral decarboxylase inhibitors: CARBIDOPA, BENSERAZIDE
c. MAO-B inhibitor: SELEGILINE
d. COMT inhibitors: TOLCAPONE, ENTACAPONE
e. Dopamine facilitator: AMANTADINE.

2. Drugs affecting brain cholinergic system

a. Central anticholinergics: BENZHEXOL (TRIHEXPHENIDYL)
b. Antihistamines: PROMETHAZINE

LEVODOPA

PERIPHERY BRAIN

Levodopa

Decarboxylase
(Vit B6 co-factor)
T
Dopamine_____________

Absorbed from GIT by active transport

Very high first pass m etabolism
Levodopa is particularly effective for bradykinesia
ADR:
On initiation o f therapy
• GI toxicity
• Postural Hypotension, Cardiac arrhythmia
• Alteration in taste sensation
• Hyperuricemia

24 HRS HELPLINE: 9891436206/9891334352

 DIAMS 38
2005 PHARMACOLOGY
On prolonged therapy
• Dyskinesias (abnormal movements)
• Hallucinations, psychosis, disorientation
• On & O ff phenomena

Note: Pyridoxine (Vit B6) abolishes the effect of levodopa by enhancing peripheral decarboxylation o f
levodopa , so less is available to cross the brain.

CARBIDOPA, BENSERAZIDE
They inhibit peripheral decarboxylation of Levodopa and make more of levodopa available tp enter the
brain. Since less o f Dopamine is available in the peripheral tissues, the side effects will be less.

LEVODOPA + TO BRAIN
CARBIDOPA

l decarboxylation in peripheral tissues

i
l side effects

BROMOCRIPTINE
D2 agonist, Used in late stages
USES:
• Parkinsonism
• Hyperprolactinemia
• Acromegaly
• Supression od lactation '■ tS. >
• Acute cocaine withdrawal syndrome

SELEGILINE
Selective MAO-B inhibitor
Neuroprotective (Disease modifying)

TOLCAPONE, ENTACOPONE
Selective COMT inhibitors. Reduce ‘on’ & ‘o ff symptoms caused by treatment o f levodopa.
Tolcapone has central and peripheral effects, more potent, hepatotoxic.
Entacapone has only peripheral effects, less potent, not hepatotoxic.

AMANTADINE
Antiviral agent, with antiparkinsonism effect (dopamine facilitator)

CENTRAL ANTICHOLINERGICS
Benzliexol (Trihexphenidyl) - DOC for drug induced Parkinsonism (particularly effective for tremors)

Note: Dmgs causing drug induced Parkinsonism

• Antipsychotics
• Metopclopramide
• Reserpine
• Methyldopa
24 HRS HELPLINE: 9891436206/9891334352
 DIAMS 39
2005 PHARM ACOLOGY

[[ d r u g s u s e d in MENTAL ILLNESS I

ANTIPSYCHOTIC |

TYPICAL ANTIPSYCHOTIC DRUGS

• Phenothiazines: Chlorpromazine (CPZ), Thioridazine, Fluphenazine
• Butyrophenones: Haloperidol, Droperidol
• Thioxanthenes: Flupenthixol

ATYPICAL ANTIPSYCHOTIC DRUGS

• Clozapine, Olanzapine, Resperidone

❖ Low potency: Chlopromazine, Thioridazine

❖ Medium potency: Clozapine
❖ High potency: Haloperidol, Fluphenazine, Olanzepine, Resperidone '

MOA: Typical antipsychotics: - Blocking D2 receptors

Atypical antipsychotics (Clozapine): - 5HT2 block, a block, D4 block
ADR:
Max with: CPZ, Thioridazine Min with: Haloperidol
• Anticholinergic (dry mouth, blurring of vision, constipation)
• a - adrenergic block (Postural hypotension)
’ • Sedation
• Hypersensitivity reactions (Cholestatic jaundice, Photosensitivity, Rashes, Dermatitis)
• Blue pigmentation of skin, corneaT&'l^tjlicular opacities - more with thioridazine

Max with: Haloperidol Min with: CPZ, Thioridazine, Clozapine

• Acute muscular dystonia (Occurs within few hrs of therapy)
• Parkinsonism (Occurs between 1-4 wks of therapy) —> DOC-
Trihexphenidyl
• Akathisia (Occurs between 1-8 wks of therapy)
• Malignant neuroleptic syndrome (Fever, rigidity, tremor, f CPK levels)—* DOC - Dantrolene
• Tardive dyskinesia (Occurs late in therapy, or after withdrawal)

Agranulocytosis (Clozapine)
Seizures (Clozapine)
Weight gain (Olanzapine)
Orthostasis (Resperidone)

USES:
Schizophrenia
Mania
Anti emetic, Preanaesthetic medication
Intractable hiccoupps - Chlorpromazine
Gille de la Tourette’s syndrome - Haloperidol
Huntington’s disease - Haloperidol

24 HRS HELPLINE: 9891436206/9891334352

 DIAMS 40
2005 PHARMACOLOGY
ANTIANXIETY DRUGS

Benzodiazepines: Diazepam, Chlordiazepoxide, Lorezepam, Alprazolam

P - blockers: Propronalol (DOC for essential tremors)
Non BZP anxiolytic: Buspirone

BUSPIRONE: Selective 5HTl A partial agonist - non habit forming anxiolytic

No action on GABA, No sedation, No dependence, No tolerance

a n t id e p r e s s a n t s !

MAO INHIBITORS
MAO-A inhibitors: Clorgiline, Moclobemide
MOA-B inhibitors: Selegiline

TRICYCLIC ANTIDEPRESSANTS
NA & 5HT reuptake inhibitors - Imipramine, Clomipramine, Amitryptyline, Doxepin
NA reuptake inhibitors - Nortriptyline, Despramine

SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRIs)

Fluoxetine, Sertaline, Paroxetine, Citalopram, Fluvoxamine

ATYPICAL ANTIDEPRESSANTS
Trazadone, Bupropion, Tianeptine, Venlafaxine, Mirtazapine
_________________________________________________________________________ _______________________________________________________

MOA inhibitors - ‘Cheese reaction’ i.e. hypertensive crisis with food containing tyramine (cheese,
chicken, red wine, liver) or w ith indirectly acting sympathomimetics

Tricyclic antidepressants
ADR: Anticholinergic (Dry m outh, blurred vision, constipation, urinary retention)
CNS: Sedation, tremors, Psychosis aggravation, mania, ataxia
CVS: Postural hypotension, Cardiac arrhyhthmia, tachycardia
Weight gain
Sexual: impotence, im paired ejaculation

Selective serotonin reuptake inhibitors (SSRIs)

FLUOXETINE
• NO Anticholinergic effect
• NO Sedative effect
• NO postural hypotension
• NO Cardiac toxicity (DOC in elder patients)
ADR: Constipation, sweating

Atypical antidepressants
TIANEPTINE: - Increases instead o f inhibiting 5-HT uptake
VENLAFAXINE: - NA and serotonin reuptake inhibitor (NSR1)

24 HRS HELPLINE: 9891436206/9891334352

 DIAMS 41
m s PHARM ACOLOGY
MIANSERIN: - Blocks presynaptic a2 receptors

USES:
• Major depression
• Obsessive compulsive disorder (OCD) - DOC is Clomipramine, 2nd choice - Fluoxetine
• Acute panic attack - DOC is Fluoxetine
• Nocturnal enuresis - DOC is Imipramine
• Migraine prophylaxis (TCA)
• Pruritis (topical Doxepin)
• Attention deficit-hyperactive disorder - Imipramine (alternative to amphetamine)
• Bulimia nervosa, Anorexia nervosa, Phobia (Fluoxetine, Imipramine)

ANTIMANIC DRUGS ||

LITHIUM CARBONATE
MOA: partly replaced body N a+ and is nearly equally distributed in and outside the cells
Not protein bound
No metabolism
Low therapeutic index (needs constant monitoring)

ADR:
Neurological - tremors (M/C) (relieved by Propronalol)
Diabetes insipidus - Thirst and polyuria (Inhibits the action o f ADH) C/I in Renal failure
Hypothyroidism
Teratogenic (Foetal goiter and Ebstein’s anomaly) C/I in pregnancy
Leucocytosis, Psoriasis ^
C/I in sick sinus syndrome

Drugs increasing levels o f Li - Diuretics, ACEIs, Jndomethacin, Tetracyclines

Toxicity
• Prophylactic level: 0.6 - 1.2 meq/1
• Therapeutic level: 08 - 1.2 meq/1
• Toxic level: > 2 meq/1

First sign of toxicity -Coarsening o f tremors, | deep tendon reflex, muscle fasciculation (neurological)
Respiratory failure
T/t: NO specific antidote
Osmotic diuretics and Sodium bicarbonate
Hemodialysis

USES:
• Acute manic episode (DOC)
• Prophylaxis and treatment o f Manic Depressive Psychosis (MDP), bipolar disorder
• Prevention of unipolar depression
• SIADH
• Cancer chemotherapy induced leucopenia and agranulocytosis

24 HRS HELPLINE: 9891436206/9891334352

 DIAMS 42
PHARM ACOLOGY
OPIOID ANALGESICS AND ANTAGONISTS ||

Endogenous opioid peptides: Enkephalins, Endorphins, Dynorphins

OPIOID RECEPTORS
1. Mu (u) receptors
Analgesia (supraspinal + spinal)
Respiratory depression
Sedation
Euphoria
Miosis
Reduction in GI motility
Physical dependence
2. Kappa ( k ) receptors
Analgesia (spinal)
Respiratory depression
Sedation
Dysphoria, Hallucinations
Miosis
Physical dependence
3. Delta (8) receptors
A nalgesia
Respiratory depression
Affective behaviour
Reduction in GI motility

I
Natural opium alkaloids: Morphine, Codeine
Synthetic opioids'. Pethidine, Fentanyl, Methadone, Dextropropoxyphene, Tramadol

MORPHINE
Agonist at p receptor (max affinity), weak agonist at k & 5 receptors
ADR: Sedation
Respiratory depression
Hypothermia
Hypotension, bradycardia
Bronchoconstriction \
Miosis I NO TOLERANCE " '
Constipation J
Urinary retention
Biliary colic
Apneoa in new bom
Idiosyncrasy & allergy
Tolerance & dependence
Acute morphine poisoning - (Antidote: NALOXONE)

USES: Strong analgesic (In severe pain o f any type - traumatic, visceral, postoperative, bums, cancer
pain, ischaemic- M I,)
Acute LVF (cardiac asthma) - reduces preload, shifts blood from pulmonary to systemic
C/I: Head injury ( | ICT)
Bronchial asthma & Respiratory insufficiency (emphysema, fibrosis, Cor pulmonale)
Hypovolemia & hypotension
Undiagnosed abdominal pain
Urinary retention
Infants& Elderly
Labour

CODEINE: more selective cough supressant

24 HRS HELPLINE: 9891436206/9891334352

 DIAMS 43
2W5 PHARMACOLOGY
PETHIDINE
Hydrolysis Meperidinic acid (major metabolite) Conjugated with
Pethidine 1 glucoronic acid
Demthylanon------ Norpethidine (minor metabolite) & excreted in
Urine
ADR: Similar to morphine + atropine like effects
Overdose - excitatory effects - tremors, mydriasis, hyperflexia, myoclonus (d/t norpethidine)
(Note: MAO inhibitors interferes with hydrolysis but not with methylation o f pethidine - which
leads to accumulation o f nor-pethidine')
USES: Preferred analgesic during
• Biliary colic
• Labour
• Preanaesthetic medication

FENTANYL
Neurolept analgesia —> Fentanyl + Droperidol
METHADONE
Used in the treatment of opioid (morphine) abstinence syndrome in opioid addicts

COM PLEX ACTION OPIOIDS AND OPIOID ANT AGONISTS 1

1. Agonist - antagonists
a) Not used as analgesic: Nalorphine
• b) Used as analgesic: Pentazocine, Nalbuphine
2. Partial/weak agonist
• Buprenorphine v ..vjf'
3. Pure antagonists v^
• Naloxone, Naltrexone, Nalmefene

PENTAZOCINE
• Agonist at k receptors (max affinity), Partial agonist / antagonist at p receptors
• 30 mg pentazocine = 10 mg morphine
• C/I in coronary ischemia, myocardial infarction (It causes tachycardia & rise in BP)

BUPRENORPHINE
• Partial p agonist, 25 times more potent than morphine, longer duration
* • Used in long lasting painful conditions e.g. cancer, postoperative pain
• It cannot be reversed by Naloxone

NALOXONE
• Competitive antagonist at p, tc & § receptors. NO agonist activity
• DOC for morphine poisoning and other opioids (except buprenorphine)

NALTREXONE
• Used for ‘opioid blockade’ therapy o f post addicts & also used to prevent relapse o f heavy
drinking
• ADR: Hepatotoxicity

24 HRS HELPLINE: 9891436206/9891334352

 DIAMS 44
2005 PHARMACOLOGY

ANTIHYPERTENSIVE DRUGS

1. ACE inhibitors: Captopril, Enalapril, Lisinopril, Ramipril

2. Angiotensin receptor antagonist: Losartan
3. Calcium channel blockers: Verapamil, Diltiazem, Nifedipine, Amlodipine
4. Diuretics: Thiazides, Furesemide, Spironolactone
5. P-blockers: Propanolol, Metoprolol, Atenolol
6. a-blockers: Prazocin, Terazocin, Phentolamine
7. a + p blockers: Labetolol, Carvedilol
8. Central sympatholytics: Clonidine, Methyldopa
9. Vasodilators: Arteriolar - Hydralazine, Minoxidil, Diazoxide
Arteriolar + Venous - Sodium Nitroprusside

ACE INHIBITORS

ANGIOTENSINOGEN --------- ► ANGIOTENSIN ------------► I

ANGIOTENSIN II

t t
RENIN ANGIOTENSIN CONVERTING
^ ENZYME

ACE INHIBITORS
Except CAPTOPRIL & LISINOPRIL —>■all ACE inhibitors af'A£])fSd;[ugs’.
ADR:
• Hypotension
• Hyperkalemia
• Dry cough (due to inhibition o f bradykinins)
• Angioedema, rash, urticaria
• Dysguesia
• Fetal damage
• Acute renal failure
USES
• Hypertension - young/ diabetes/Angina/Post ME CHF/ Asthma/PVD/Gout
• CHF - first line drugs of choice (j, preload & j afterload), Cardiac remodeling.
• HT with Diabetic nephropathy (reduces proteinuria)
• MI - improves survival
• Scleroderma crisis

CONTRAINDIACTIONS
• Pregnancy
• B/L renal artery stenosis
• Hyperkalemia (should not be given with K+ sparing diuretics-SPIRONOLACTONE)
♦♦♦ Single kidney
• Acute renal failure

24 HRS HELPLINE: 9891436206/9891334352

 DIAMS 45
2005 PHARMACOLOGY

ANGIOTENSIN RECEPTOR (ATI) ANTAGONISTS

Losartan
• Long acting metabolite
• Used as hypertensive alternative to ACE inhibitors (d/t less chances o f dry cough, dysguesia,
ra sh ,)
• Hyperuricemic

CALCIUM CHANNEL BLOCKERS

Suitable for hypertensive AVOID in
• Elderly -C H F
• Pregnant - Conduction defects
• Asthma/ Angina/ COPD/ PVD - Diabetes
• Isolated systolic hypertension

DIURETICS
Indicated for hypertensive AVOID in
• Elderly - Young
• Obese with volume overload - Diabetes
• Low renin hypertension - Gout
- Pregnancy
- Abnormal lipid profile
l BLOCKERS
Ihdicated for hypertensive
• Young, non-obese hypertensive, esp; with psychological stress, anxiety
• Angina/post MI ^ . ',VV\

AVOID in
• CHF
• Conduction defects & bradycardia
• Asthma
• PVD
• Diabetes
• Abnormal lipid profile
• Prinzmetal angina
• Elderly

a - BLOCKERS
Prazocin
Competitive a l blocker
ADVANTAGES: Improves carbohydrate metabolism
Improves lipid profile
Improves co-existing PVD or BPH

ADR: Postural hypotension and fainting in the beginning (First dose effect)

24 HRS HELPLINE: 9891436206/9891334352

 DIAM S 46
2005 PHARMACOLOGY

CENTRAL SYMPATHOLYTICS ||

Clonidine
• Selective a2 agonist,
• Stimulates a2 receptors in medulla (vasomotor centre) —» j in sympathetic outflow —> j. BP &
HR
Uses: Opiod withdrawal
Alchohol withdrawal
Smoking cessation
Diabetic neuropathy
ADR: Rebound hypertension on sudden withdrawal
Sedation
Impotence

Methyldopa
• Selective a2 agonist, MOA same as clonidine
• DOC for hypertension in PREGNANCY
ADR: Sedation
C oom b’s positive hemolytic anemia
Drug induced lupus syndrome
Rebound hypertension
Parkinsonism, hyperprolactinemia

v a s o d il a t o r s ! !
_______ .— ’1 '\'v>>\.?\'v.

Hydralazine I
Arteriolar vasodilator i
M etabolised by acetylation
ADR: Reflex tachycardia T/t: (3 blocker is combined
Salt and water retention — edema (due to fed renin release) T/t: Diuretic is combined
Lupus like syndrome
Precipitates angina & MI
DOC for hypertensive emergency in PREGNANCY (Preeclampsia)

M inoxidil
Arteriolar vasodilator, K+ channel opener
USES: Severe hypertension
Topically for Alopecia (male pattern baldness)

Diazoxide
Direct acting arteriolar vasodilator, K+ channel opener
USES: Hyperytensive emergency
Insulinoma (before definitive therapy can be initiated)
ADR: Hyperglycemia (fes insulin secretion)
Salt and water retention

24 HRS HELPLINE: 9891436206/9891334352

 DIAMS 47
2005 PHARMACOLOGY
Sodium nitroprusside
Direct acting vasodilator, acts on both arteries and veins (J, Preload & Afterload)

USES: All types o f Hypertensive emergencies:

• Malignant hypertension (Hypertensive encephalopathy )
• Acute aortic dissection (along with (3 blocker-Esmolol)

HYPERTENSIVE EMERGENCIES
Drugs used in hypertensive emergencies:
Sodium Nitroprusside Enalaprilat Nifedipine (ORAL)
Nitroglycerin Hydralazine Phentolamine
Diazoxide Labetolol Trimethophan
Fenoldopan Nicardipine
Esmolol Urapidil

• Malignant hypetension (Hypertensive encephalopathy) - Sodium Nitroprusside

• Hypertensive emergency in MI, unstable angina, LVF - Nitroglycerin
• Acute aortic dissection - Sodium nitroprusside along with ft blocker-Esmolol
• Hypertensive intracranial hemorrhage - Nicardipine, Nimodipine
• Hypertensive emergency in pregnancy (preeclampsia) - Hydralazine
• Hypertensive emergency with pulmonary edema - Loop diuretics, Morphine
• Hypertensive crisis in Pheochromocytoma - Phentolamine

ANTIHYPERTENSIVES USED IN PREGNANCY

• Methyldopa (DOC) ^
• Hydralazine (DOC in preeclampsia)
• Nifedipine
• Diazoxide
• Sodium nitroprusside (Drug of last resort for acute HT)

24 HRS HELPLINE: 9891436206/9891334352

 DIAMS 48
2005 PHARMACOLOGY

|1 ANTIANGINAL D R U G S !

N ITR A TES
a) Short acting: Glyceryl trinitrate(GTN, Nitroglycerine), S/L Isosorbide Dinitrate
b) Long acting: Oral Isosorbide Dinitrate
Isosorbide Mononitrate
Pentaerythritol tetranitrate
All nitrates undergo extensive first pass metabolism except Isosorbide mononitrate
Ca+

N IT R O D IL A TO R S

MOA:
Denitration o f nitrates in the SM cell —> Release o f nitric oxide (NO) —> activates GUANYLYL
CYCLASE —» fed cGMP —> Reduces Ca++ entry & causes dephosphorylation o f MLCK —»
Inactivation o f myosin and it fails to interact with actin to cause contraction —> Relaxation occurs.

• Venodilatation —» j Preload
• Arteriolar dilatation —> j Afterload
• l 0 2 consumption & Redistribution of coronary blood flow (does not f coronary flow)

ADR: Vasodilatation: Throbbing headache (M./C- temporal), Tachycardia, orthostatic hypotension

Tolerance
Methemoglobinemia

USES: Angina pectoris (acute attack) —» GTN, S/L Isosorbide dinitrate

CHF and acute LVF
Cyanide poisioning
24 HRS HELPLINE: 9891436206/9891334352
 DIAMS 49
O tw 3 PHARMACOLOGY
c a l c iu m c h a n n e l b l o c k e r s
> Phenylalkamines (cardioselective) : VERAPAMIL
> Benzothiazepine (intermediate) : DILTIAZEM
> Dihydropyridines (vasculoselective): NIFEDIPINE
NICARDIPINE, NIM ODIPINE, AMLODIPINE

Channel types: L- type (mainly cardiac & smooth muscles) —> M ost CCBs
T- type (Cardiac & neuronal) —> Ethosuximide, Mibefradil, Flunarizine
N-type (Neuronal)
MOA:
• Inhibition o f Ca+ entry to heart muscle fibres —» J, myocardial contractility —> J, 0 2 demand
• Smooth muscle relaxation (esp vascular) —> l BP —> f afterload

a* Suppression o f contractility, AV conduction, automaticity - Verapamil > Diltiazem >Nifedipine

> Vasodilatation (coronary, pulmonary, pheripheral) - Nifedipine > Verapamil > Diltiazem
> Vasodilatation o f Cerebral arteries: - Nimodipine

ADR: Tachycardia (with Nifedipine), orthostatic hypotension

Aggravation o f CCF, Diabetes,
AV block (verapamil) —> Note: p blockers should not given with CCBs.
Constipation, ankle edema, leg cramps
USES:
• Angina pectoris (Prinzm etal’s, exertional, unstable) —» Nifedipine, Nicardipine
1 • Cardiac arrythmias —» {(PSVT - Verapamil), Diltiazem}
• Hypertension —» Nifedipine
• Intracranial hemorrhage (to imprqye neurological deficits) Nimodipine
• Migrane —> Flunarizine %
• CCF —» N ifedipine
• Hypertrophic cardiomyopathy —> Nifedipine (alt to p blockers)
• Nocturnal leg cramps, Raynaud’s disease.
CO NTRAINDICATIONS
• CCF
• Diabetes
• Conduction defects (AV block)

p BLOCKERS
i HR, i cardiac force, j BP
• Prophylaxis only, no value in acute attack.
• Most effective drugs for prevention o f sudden cardiac death in Post MI.
• Contraindicated in Prinzm etal’s angina / CCF / AV block / A sthm a / Diabetes / PVD

POTASSIUM C H A N N E L O PE N E R S: MINOXIDIL, DIAZOXIDE, NICORANDIL

O THERS:
Dipyrimidamole: Coronary dilator, antiplatelet drug (inhibits uptake o f adenosine)
Coronary steal phenomenon (Pharmalogical success, therapeutic failure)
Trimetazidine: New Calcium channel blocker, Cytoprotective effect (M aintains LV function in
presence o f ischaemia, without affecting hemodynamics), Used in stable angina.

24 HRS HELPLINE: 9891436206/9891334352

 DIAMS 50
PHARMACOLOGY

|1 CARDIAC GLYCOSIDES AND DRUGS FOR CHF

CARDIAC G L Y C O SID E S]!

DIGOXIN, D IG IT O X IN
Contains steroid nucleus + Sugar residue

D IG ITO XIN DIGOXIN

Source Digitoxin purpurea Digitalis lanata
Oral absorption V.good (90 - 100%) Good (60 - 80%), IN also
Plasma protein binding 95% 25%
Plasma t'A 5 - 7 days 40 hrs
Elimination Hepatic metabolism Renal excretion
Uses Maintenance Routine t/t & emergency

MOA:

Inhibition of Na+ - K+ ATPase of myocardial fibres —> f N a intracellularly —>Less Ca+ goes out o f
cell —► t Contraction.

Cardiac Effects
Mechanical effects: ] force o f contraction, j CO Electrophysiological effects: Early vagomimetic
| HR Late Arrythmogenic
l 0 2 consumption
(Systole is shortened, Diastole prolonged)
Uses: CHF
Atrial fibrillation / flutter (DOC for controlling ventricular rate in AF or AF1)

24 HRS HELPLINE: 9891436206/9891334352

 DIAMS
2005 PH A R M A C O L O G Y
ADR: (Narrow margin o f safety) —> Dose orally: 0.05 - 0.1 m g/kg (adult)
Therapeutic dose: 0.8 - 1.5 ng/ml
Toxicity: > 2.4 ng/ml
• Gastric irritance- Vomiting, Nausea, (earliest symptom)
• Cardiac:
o Ventricular premature beats (VPB), bigeminy (M/C)
o Partial or complete heart block
o Supraventricular arrhythm ia, Ventricular tachycardia, ventricular fibrillation
• Disturbance in yellow-green vision
• Gynecomastia

Digitalis toxicity can be enhanced by:

• Hypokalemia
• Hypomagnesemia
• Hypercalcemia
• Hypothyroidism (Myxeedema)
• Drugs: Diuretics, Amiodarone, CCBs, Quinidine, Erythromycin,

T/t of Digitalis toxicity

• Mild toxicity - Potassium supplements
• Ventricular arrhythmia - Lidocaine
• Supraventricular arrhythmia - Propanolol
• AV block & bradycardia -A tro p in e
I • Severe toxicity - DIGIBIND (Fab fragments o f digoxin antibodies)

C/I of Digitalis '\ ^

• Hypertrophic cardiomyopathy Nv ^
• Ventricular tachycardia
• Partial or complete AV block
• Constrictive pericarditis
• Mitral stenosis
• Myocarditis
• High output failure (Anemia, thyrotoxicosis)
• Diastolic heart failure
• WPW syndrome

DRUGS FOR CH F ||

> Diuretics: Loop diuretics / thiazides / spironolactone —> (.[ preload)

> Vasodilators
■ Venodilators ({ preload):- Nitrates (GTN, Isosorbide dinitrate)
■ Arteriolar dilators ([ afterload):- Hydralazine, Nifedipine, M inoxidil, Nicorandil
■ Arteriolar and venodilators (l preload & j afterload):- A CEIs, Losartan, Prazosin,
Phentolam ine, Nitroprusside
> Cardiac stim ulants
■ Dopamine, Dobutamine
■ PDE III inhibitors (Inodilators): Milrinone, Amrinone (ADR:- thrombocytopenia, hepatitis)
24 HRS HELPLINE: 9891436206/9891334352
 DIAMS 52
2005 PHARMACOLOGY

ANTIARRHYTHMIC DRUGS

Class I - SODIUM CHANNEL BLOCKERS (local anaesthetic action)

A. Quinidine, Procainamide, Disopyramide, Moricizine
B. Lidocaine, Phenytoin, Mexiletine, Tocainide
C. Flecanide, Encainide, Propafenone

Class II - p BLOCKERS
Propranolol, E sm o lo l, Sotalol

Class III - POTASSIUM CHANNEL BLOCKERS

Amiodarone, Bretylium, Ibutilide, Dofetilide, Sotalol

Class IV - CALCIUM CHANNEL BLOCKERS

Verapamil, Diltiazem

OTHERS: For PSVT: Adenosine, Verapamil

For AV block: Sympathomimetics (Isoprenaline)
Anticholinergics (Atropine)
For AF, AF1: Digitalis

Quinidine
Adv: GIT intolerance, hypersentivity
Cinchonism - tinnitus, loss of hearing, blurred vision
Cardiac toxicity - Paradoxical tachycardia (P re v e n te d ^ gr^pr digitalization)
Torsades de pointes, Hypotension, hearCblobJc.
Procainamide I
Metabolised by acetylation
Adv: Drug induced Lupus
Agranulocytosis

Disopyramide: Additional anticholinergenic action (dry mouth, urinary retention, blurred vision)

Lidocaine
High first pass metabolism in liver, hepatic blood flow dependent. Rapidly distributed
Adv: CNS toxicity: drowsiness, convulsions
DOC for ventricular arrhythmias d/t digitalis toxicity, following MI, during cardiac surgery.

Propranolol
High first pass metabolism in liver, hepatic blood flow dependent
USES: Reduces mortality in Post-MI by preventing ventricular arrhthymias
Sinus tachycardia, digitalis induced tachyarrhythmias, Sick sinus syndrome.

Esmolol
Ultrashort acting |31 blocker.
USES: DOC for Emergency control o f ventricular rate in AF / AF1
DOC for arrhythmias during anaesthesia / surgery

24 HRS HELPLINE: 9891436206/9891334352

 DIAMS 53
2005 PH ARM ACOLOGY
Amiodarone
Iodine contaning, long acting anti arrhythmic (t'A - 3-8 weeks)
K+ channel blocker, Na+ channel blocker, Ca+ channel blocker.
USES: Refractory ventricular tachycardia (VT), Recurrent VF
WPW syndrome
DOC for Chronic therapy and prophylaxis of VT, VF, AF, AF1
ADV:
• Pulmonary fibrosis
• Peripheral neuropathy
• Photosensitization
• Comeal microdeposits, blue skin pigmentation
• Hypothyroidism, Hyperthyroidism
• Tremors, ataxia
• Liver damage

Bretylium: Main use is in VT or VF refractory to electrical defibrillation.

Ibutilide, Dofetilide: Pharmalogical cardioversion of AF or AF1 to normal sinus rhythm.

Adenosine:
• DOC for PSVT
• Rapid action (30 sec)
• Very short t'A in blood (10 sec)
• Dipyridimole jes the effect o f adenosine by inhibiting its uptake.
; • Theophylline / Caffeine je s its effect (blocks adenosine receptors)

CHOICE OF DRUGS FOR CARDIAC ftRRIIYTIIMIAS

' T _____ __ ________i ____ x _______•
i • ________ x *
Type of arrhythmia Choice in acute therapy
a
Choice in chronic therapy
1. Atrial flutter (AF) —> Conversion Cardioversion A miodarone / Quinidine

—> Control Esmolol D igoxin

Ventricular rate
2. Atrial fibrillation (AF) —> Cardioversion A miodarone / Quinidine
Conversion
—» Control Esmolol D igoxin
Ventricular rate
-■> Ventricular tachycardia (VT) A m iodarone / Quinidine
Lignocaine / Cardioversion

4. Ventricular fibrillation (VF) Electrical defibrillation A miodarone

5. Paroxysmal supraventricular Adenosine - 1st choice D igoxin, verapamil

tachycardia (PSVT) Verapamil - 2nd choice
6. Ventricular extrasystole (VES)
—* Acute MI Lignocaine
—> Digitalis induced Lignocaine / Pot. Chlor
7. Wolff-Parkinson Syndrome (W PW ) Cardioversion / Flecainide Am iodarone / Propranolol

8. Torsades de pointes Pacing Propranolol

24 HRS HELPLINE: 9891436206/9891334352

 DIAMS 54
2005 PHARMACOLOGY

DIURETICS
Classification
1. LOOP DIURETICS
2. THIAZIDE DIURETICS
3. POTASSIUM SPARING DIURETICS
4. CARBONIC ANHYDRASE INHIBITORS
5. OSMOTIC DIURETICS

1. Loop Diuretics (eg: Furesemide)

2. Thiazides
3. Aldosterone antagonists (eg: Spironolactone)
4. Carbonic anhydrase inhibitors (eg: Acetazolamide)
5. Osmotic agents (eg: Mannitol)

24 HRS HELPLINE: 9891436206/9891334352

 DIAMS 55
2005 PHARM ACOLOGY
1. LO O P DIURETICS (Frusemide, Ethacrynic acid)

MOA: Inhibits Na+ K+- 2 0 " cotransport

Site of action: - Thick ascending linb of loop of Henle
Quick onset & Short acting
USES: Edematous states of cardiac, hepatic or renal origin.
Acute Pulmonary edema (acute LVF) —» Additional vasodilator action
Antihypertensive (only in case o f renal insufficiency, CHF)
Forced diuresis in poisoning
Hypercalcemia
ADR:
• Hypokalemia
• Hyponatremia
• Hypovolemia
• Hypocalcemia
• Hypomagnesiemia
• Hyperuricemia
• Metabolic alkalosis
• Sulphonamide allergy - hypersensitivity
• Ototoxicity (Ethacrynic acid)
• Most marked Cl” excretion (Ethacrynic acid) —>can lead to hypochloremic alkalosis.

2. THIAZIDES DIURETICS (Chlorthiazide, Hydrochlorthiazide, Indapamide, Chlorthalidone)

\lO A : Inhibits Na+ Cl” symport.
Site of action: - Early DCT
Longer acting (longest acting -4 Uilorthalidone (48 hrs))
USES: Edematous states
Hypertension (first line of diuretics)
Nephrogenic Diabetes insipidus
Hypercalciuria, Osteoporosis
ADR:
• Hypokalemia H ypercalcem ia
• Hyponatremia Hyperglycemia
• Hypovolemia Hyperlipidemia
• Hypomagnesiemia Hyperuricemia
• ADH like action

C/I: Diabetes, Gout, Renal failure, Pregnancy.

3. POTTASIUM SPARING D IU R E T IC S (Spironolactone, Amiloride, Triamterene)

Spironolactone (Aldosterone antagonist)

MOA: Binds to Mineralocorticoid Receptor (MR), which is the binding site o f aldosterone, —*
| expression of genes (AIP), controlling Na+ channels, hence natriuretic action & j K+ secretion.
Site of action: Only diuretic that acts from interstitial side of the tubular cell, at Late DCT & CT

A m iloride: Blocks the luminal Na+ channels at late DCT & CT

24 HRS HELPLINE: 9891436206/9891334352

 DIAMS 56
2005 PHARM ACOLOGY
USES: Along with loop diuretics & thiazides, to prevent hypokalemia
Primary hyperaldosteronism
Refractory Edema a/w secondary hyperaldosteronism (CHF, Cirrhosis, Nephrotic syndrome)
ADR: Hyperkalemia (C/I with ACEIs)
Metabolic acidosis
Gynecomastia, Menstrual irregularities, hirsutism (antiandrogenic action)

4. CARBONIC ANHYDRASE IN H IB IT O R S (Acetazol amide)

MOA: Inhibition of Carbonic anhydrase (CA)

Site of action: PCT

USES: Glaucoma
Acute mountain sickness
To alkalinise urine: for UTI & excretion of acidic drugs
ADR: Hypokalemia (Cause m ost marked kaliuresis among all diuretics)
Metabolic acidosis
May precipitate hepatic encephalopathy

5. MANNITOL
MOA: Osmotic uphold o f water in PCT
USES: Cerebral edema & Acute congestive glaucoma (J. intracranial and intraocular tension)
Hemolysis & rhabdomyolysis
Forced diuresis in poisonings

C/I: Acute tubular necrosis (ATN) v

Anuria
Acute LVF
Pulmonary edema
Intracranial hemorrhage

ANTIDIURETICS ||

ADH AGONISTS:
> Vasopressin, Qesmopressin
> Thiazide diuretics
> Others: Chlorpropamide, Carbamazepine, Clofibrate.

ADH ANTAGONISTS: Demiclocycline, Lithium. -> Used in SI ADH

Vasopressin
Uses:
• Diabetes insipidus (V2 action)
• Bed wetting in children & N octuria in adults (V2 action)
• Haemophilia, Von W illebrand’s disease (V2 action)
• Bleeding esophageal varices (Vi action)

24 HRS HELPLINE: 9891436206/9891334352

 DIAMS 57
2005 PHARMACOLOGY

DRUGS AFFECTING COAGULATION, BLEEDING & THROMBOSIS

a n t ic o a g u l a n t s !

Classification
Parenteral anticoagulants: Heparin, LMWH, Heparinoids
Oral anticoagulants: Warfarin, Dicumarol, Ethylbiscoumacetate, Phenindione

HEPARIN ORAL ANTICOAGULANTS

1. Chemistry Mucopolysaccharide Small lipid soluble molecule
(10000-20000 MW)
2. Route of admin Parenteral, (I/V, SC) Oral
3. Onset of action Rapid Delayed (1-3 days)
4. Duration of action 4 - 6 hrs 3 - 6 days
5. Activity In vitro and in vivo In vivo
6. MOA Activates Antithrombin III i synthesis of II, VII, IX, X
,7. Monitor APPT PT
8. Antagonists Protamine sulphate Vit. Ki (Phytonadione)
9. Placental barrier Does not cross placenta Chondrodysplasia punctata
}0.Use To initiate therapy For maintainance
11 .Adverse effects • Bleeding Bleeding
• Thromhp.cytp|renia
• Osteoporosis

LMW H (Low molecular weight Heparin)

• Molecular wt: < 5000
• Acts selectively on factor Xa
• Do not interact with platelets so does not cause thrombocytopenia
• APTT is not much prolonged, so no need o f monitoring APTT
• Less bleeding
• Single dose per day (long t'A)

USES: DVT, Pulmonary embolism, MI, Unstable angina, RHD, AF, Vascular surgery, Prosthetic heart
valves, DIC

COAGULANTS H*•

1. Vitamin K
• Kl (from plants): Phytonadione
• K2 (from bacteria): Menaquinone
• K3 (synthetic): Menadione
2. Miscellaneous: Fibrinogen, Antihaemophiiic factor, Ethamsylate

24 HRS HELPLINE: 9891436206/9891334352

 DIAMS 58
2005 PHARM ACOLOGY

FIBRINOLYTICS (THROMBOLYTICSTII

EXTRINSIC INTRINSIC
Streptokinase Factor Xlla
Urokinase ACTIVATORS Kallikrein
r tPA t-PA FIBRIN (insoluble)

___________ - t
PLASMINOGEN --------------- ► PLASMIN
T
EACA FIBRIN (soluble)
Tranexaemic acid 1___ INHIBITORS a-Antiplasmin
Aprotinin f a-Macroglobulin

MOA: Activation of Plasminogen —» Plasmin and lysis of clot.

Streptokinase
• Obtained from P haemolytic streptococci group C
• Less clot specific, Half life (15-25 min)
• Antistreptococcal antibodies present d/t past infection neutralize the dose o f Streptokinase.
ADR: Allergic reactions: Anaphylaxis, fever, arrhythmias, Hypotension

Recombinant tissue plasminogen activator (r tPA), (Alteplasej '

• Derived by recombinant DNA technique
• Clot specific -Specifically activates plasminogen bound to fibrin and avoids systemic activation
• No allergic reactions, short half life (4-8 min)
• Reocclusion common —> Heparin infusion required

Urokinase: Extracted from cultured human kidney cells

Reteplase: Mutated (Modified) form o f Human tP A, Longer duration of action

Acylated plasminogen-streptokinase activator (APSA)

USES o f fibrinolytics
• Acute MI within first 12 hrs.
• DVT
• Pulmonary embolism
• Peripheral arterial occlusion
Toxicity
• Bleeding —>cerebral hemorrhage
• Allergic reactions with Streptokinase —»■anaphylaxis, bronchospasm, rashes, angioedema
• Hypotension

24 HRS HELPLINE: 9891436206/9891334352

 DIAM S 59
2005 PHARMACOLOGY

Contraindications
• Previous cerebrovascular stroke
• Marked hypertension
• Bleeding disorders, active internal bleeding excluding menses
• Peptic ulcers
• Recent trauma
• Surgery, biopsies

ANTIFHHHNOLYTTOjjl
MOA: Inhibit plasminogen activation and dissolution o f clot.

• Epsilon amino-caproic acid (EACA)

• Tranexaemic acid
• Aprotonin

^m PLA TC LETD R U G S^*

• Aspirin: Inhibits COX enzyme, hence Thromboxane A2 (TXA2) synthesis (platelet aggregator)
• Ticlodipine: Alters ADP receptors on platelet membrane.
• Clopidogrel: Alters ADP receptors on platelet membrane.
• Dipyridimole: Inhibits uptake o f adenosine.
* • Tirofibam, Abciximab, Eptifibatide: Glycoprotein lib / Ilia receptor antagonists.

USES:
Unstable angina
Post MI
Post stroke
Post PTCA
TIA
PVD
Prosthetic heart valves & arteriovenous shunts.

24 HRS HELPLINE: 9891436206/9891334352

 DIAMS 60
2005 PHARMACOLOGY

DRUGS FOR PEPTIC ULCER

PIRENZEPINE CIM E U D IN E | h s (Sprdsto l

X
L---- ----------------------------—

Ach ^|His PG ^ Gastrin

a. Drugs reducing gastric acid secretion

• H2 antihistaminics: Cimetidine, Ranitidine, Famotidine
• Proton pump inhibitors: Omeprazole, Pantoprazole, Rabeprazole
• Anticholinergics'. Pirenzepine (M l)
• Prostaglandin analogues: M isoprostol
b. Drugs that neutralize acid
• Systemic: Sodium bicarbonate
• Non-systemic: Magnesium Hydroxide, Aluminium hydroxide
c. Ulcer protectives:
• Sucralfate, Colloidal bismuth subcitrate (CBS)
d. Ulcer healing drugs
• Carbenoxolone sodium
e. Anti-H.pylori drugs
• Amoxicillin, Clarithromycin, Metronidazole

H2 antihistam inics

C im etidine
Adr: Antiandrogenic action (Gynecomastia, impotence) —►(NOT other H2 blockers)
Fever & neutropenia
Inhibition of cytochrome P450 (enzyme inhibitor, so fes blood levels of many drugs)
24 HRS HELPLINE: 9891436206/9891334352
 DIAMS
2005 PHARMACOLOGY
pplH
• Hit & Run drugs
• Inhibits H+ - K+ ATPase irreversibly, i.e. action until new H+ - K+ ATPase is synthesized
• Uses:
Peptic ulcer
Reflux esophagitis
DOC for Zollinger-Ellison disease

Prostaglandin analogues (PGE2, PGI2) [

• Cytoprotective: [ acid secretion and f mucous + -HC03 production
• AD V : Diarrhea, Abdominal cramps, uterine bleeding, abortion.
• Used in the prevention of NSAIDs induced gastric injury

Anticholinergics
Pirenzepine: selective M l blocker, inhibits gastric acid secretion without producing atropinic S/E

Antacids
• Magnesium hydroxide salts are fast acting (prompt effect), laxative ; "
• Aluminium hydroxide salts are slow acting (sustained effect), constipating

So Combination o f Magnesium hydroxide & Aluminium hydroxide used

Antacids J,es absorption of Tetracyclines, Quinolones, Ketoconazole, Digitalis

jUlcer protectives
Sucralfate: Polymerizes at pH < 4, (T)ote: Antacids should N O T given with sucralfate)
■V'SyyVV
Colloid bismuth: fes mucous and bicarbonate ^
Has anti H-pylori effect also
Adr: Prolonged use - bismuth toxicity Osteodystrophy, Encephalopathy

Ulcer healing drugs

Carbenoxolone sodium: f mucous production, Stimulates collagen activity at base of ulcer, and its
epithelisation.
ADR: Na+ and water retention, hypokalemia

Anti H-pylori drugs

3 drug regimen
PPI (Omeprazole) +Amoxicillin + Clarithromycin OR
PPI (Omeprazole) + Metronidazole + Clarithromycin OR
PPI (Omeprazole) + Amoxicillin + Metronidazole

4 drug regimen:
PPI + Tetracycline + Colloid bismuth + Metronidazole

24 HRS HELPLINE: 9891436206/9891334352

 DIAM S 62
2005 PHARMACOLOGY

|[ EMETICS & ANTIEMETICS]|

EMETICS ||
Apomorphine, Ipecacuanha

A N T IE M E T IC Sl
Anticholinergic: Hyoscine, Dicyclomine
H I antihislaminics: Promethazine, Cyclizine, Diphenhydramine, Cinnarizine
Neuroleptics: Chlorpromazine
Prokinetics: Metoclopramide, Domperidone, Cisapride
5HT3 antagonists: Ondansetron, Granisetron
Others: Dexamethasone, Cannabinoids

I h 'oscine: M ost effective drug for motion sickness

Dicyclomine: Morning sickness

C innarizine: Antivertigo drug and is also protective for motion sickness

N euroleptics: Block D2 receptors on CTZ

M etoclopram ide:
• D2 antagonist on CTZ, Cholinomimetic, 5-HT3 antagonism
• Prokinetic & | tone o f lower esophageal sphincter^
• ADR: Parkinsonism, Galctorrhoea, Gynecomastia, Sedation, dizziness
Abolishes therapeutic effect o f levodopa
• USES: Antiemetic - postoperative, drug induced, etc
For emergency general anaesthesia in a patient who has food food < 4 hrs before
Useful in GERD

D om peridone:
• D2 antagonist
• Does not cross BBB, so no extrapyramidal effects & does affect action o f levodopa

C isapride:
• 5HT4 receptor agonist
• ADR: Diarrhea, Torsades de pointes with erythromycin / clarithromycin / ketoconazole

O ndensetron, G ranisetron:
• 5HT3 antagonists
• Useful as antiemetic in chemotherapy, Radiotherapy induced vomitings

D IG E ST A N T Sl
M ethyl polysiloxane
A silicon polymer - ‘Antifoaming agent’ reduces surface tension and collapses froth.
Used in acid peptic disease, flatulence, GERD
24 HRS HELPLINE: 9891436206/9891334352
 DIAMS 63
2005 PHARMACOLOGY

GALL STONE DISSOLVING DRUGS]|

Chenodiol (chenodeoxycholic acid) - j, cholesterol synthesis in liver (inhibits HMGCO-A reductase)

Ursodiol (Ursodeoxycholic acid) - J, absorption o f cholesterol in intestine

Criteria for medical t/t o f gall stones:

• Radioulcent stone (cholesterol stone)
• Smaller stones < 1 5 mm size
• Functioning gall bladder
C/I o f medical t/t: PREGNANCY

24 HRS HELPLINE: 9891436206/9891334352

 DIAMS 64
2005 PHARMACOLOGY

ANTIMICROBIALS

GENERAL CONSIDERATIONS

CLASSIFICATION OF ANTIMICROBIALS
I. Based on MOA

Inhibitors of DNA
Inhibitors O f Metabolism Function
SULFONAMIDES QUINOLONES
TRIMETHOPRIM PABA DNA RIFAMPICIN
PYRIMETHAMINE METRONIDAZOLE
DAPSONE
METHOTREXATE
THFA Cause Cell M embrane

Inhibitors O f Cell Wall

Synthesis
oooa Leakage
POLYMIXIN
COLISTIN
PENICILLINS AMPHOTERICIN B
CEPHALOSPORINS NYSTATIN
VANCOMYCIN Inhibitors O f Protein Synthesis HAMYCIN
CYCLOSERINE TETRACYCLINES
BACITRACIN AMINOGLYCOSIDES
MACROLIDES * A A 'A
ERYTHROMYCIN \
CLINDAMYCIN
II. Based on type of action

BacterioSTATIC BacterioCIDAL

• Penicillin
• Sulfonamides • Cephalosporins
• Etambutol • Aminoglycosides
• Erythromycin • Cotrimoxazole
• Chloramphenicol • Ciprofloxacin
• Tetracycline • INH, RIF, PYZ
• Vancomycin

III. Based on source of derivation

FUNGI ACTINOMYCETES BACTERIA

Penicillins Tetracyclines Polymixin
Cephalosporins Aminoglycosides Colistin
Griseofulvin Macrolides Bacitracin

24 HRS HELPLINE: 9891436206/9891334352

 DIAMS 65
2005 PHARMACOLOGY

INHIBITORS OF CELL WALL SYNTHESIS ||

I. B-LACTAMS ANTIBIOTICS

PENICILLINS CEPHALOSPORINS MONOBACTUMS

Limited spectrum First Generation

Penicillin G (parenteral) Cephalexin Aztreonam
• Procaine Pen G Cephadroxil
• Benzathine Pen G Cefazolin
Penicillin V (oral)
Second generation
Penicillinase resistant Cefiiroxime
Methicillin Cefaclor CARBEPENEMS
Nafcillin Cefamandole
Oxacillin Cefofetan Imipenem/cilastatin
Cloxacillin Cefoxitin Meropenem

Wider spectrum Third Generation

Aminopenicillins : A m picillin Cefotaxime
A m oxycillin Ceftazidime
jparboxypenicillins: Carbenicillin Ceftriaxone
i Ticarcillin Ceftriaxone
Ureidopenicillins: Azlocillin Cefaperazone
M ezlocillin c£efixime
Piperacillin Cefdinir
Mecillinam Moxalactum

P-lactamase inhibitors Fourth Generation

Clavulanic acid Cefepime
Salbuctam Cefpirome

II. OTHERS: Vancomycin, Teicoplanin, Bacitracin

PENICILLINS 1
----------------------
• Binds to penicillin binding proteins (PBPs) o f bacterial cell wall —» inhibition of
Transpeptidase—^formation of spheroplast or long filaments a b a c te ria l lysis
• Very rapid RENAL excretion
• Spectrum: Gram +ve cocci and bacilli mainly, meningococci
• 1 gm = 1.6 m illion Units OR 1 MU = 0.6 gm

ADR: Penicillin G: Allergy-anaphylaxis, may cause Jarisch Herxheimer reaction in syphilis

Methicillin: interstitial nephritis
Oxacillin: Hepatitis
Nafcillin: N eutropenia
Ampicillin- diarrhea, produces rash in EBV infection, in AIDS, Pseudomembranous colitis

24 HRS HELPLINE: 9891436206/9891334352

 DIAMS 66
2005 PHARMACOLOGY
Uses:
Penicillin G
• DOC in Menningococcal meningitis, Syphilis, Streptococcal infections (Pharyngitis, Otitis
media, Scarlet fever, SABE and Rheumatic fever), Yaws, Anthrax, Actinomycosis, Listeria
infection, Rat bite fever.
• Prophylatic uses: Rheumatic fever, syphilis, Infective endocarditis
Penicillinase resistant penicillins (Methicillin) are the DOC for penicillinase producing
staphylococcal infections.
Ampicillin is the DOC for UTI in pregnancy.
Used in t/t o f typhoid carriers & cholecystitis (attaines a higher concentration level in GB)
Antipseudomonas drugs: Carbenicillin, Ticarcillin, Piperacillin. Azlocillin.

CEPH A LOSPO RIN S

ADR:
• Thrombocytopenia, Hypoprothrombonemia / Disulfram like reaction-
cephalosporins containing MTT ring:-Cefamandole, Cefoperazone, Cefofetan,
Moxalactum)
• Nephrotoxicity: (Cephaloridine-Most nephrotoxic)
• Diarrhea (Cefoperazone)
• Cholelithiasis (Cefoperazone, Ceftriaxone)
• Neutropenia (Ceftazidime)
USES:
• Spectrum o f 1st generation:- penicillinase producing staphylococci and streptococci
• Spectrum of 2nd generation:- spectrum of 1st generation + gram negative but NOT active
against pseudomonas. N‘
• Spectrum of 3rd generation:- broad spectrum, gram A iegative rods (Klebsiella, Proteus,
Enterobacter, Hemophilus) and hospital acquired infections, less activity against gram +ve, but
no activity against methicillin resistant staphylococci, enterococcus.
• A ntipseudom anal drugs: Ceftazidime, Cefoperazone, Ceflpime
• Ceftriaxone is DOC in t/t o f bacterial meningitis (Meningococcal, Hemophilus), Gonorrohea,
Chancroid, salmonellosis and typhoidfever in children.

MONOBACTUMS
Aztreonam:
• Active against gram negative and pseudomonas, no activity against gram +ve
• Lack of cross sensitivity with other B-lactams, so can be used in patients allergic to penicillin
or Cephalosporins.

CARBAPENEMS
Imipenem: Rapid hydrolysis by the enzyme dihydropeptidase I o f renal tubular cells so given in
combination with cilastatin (inhibitor of dihydropeptidase I) Antipseudomonal activity

VANCOMYCIN
DOC for Methicillin resistant staphylococcus aureus (MRSA)
Also used fox Antibiotic associated Pseudomembranous colitis (DOC is Metronidazole)
ADR: Red man sydrome (Flushing and erythema of head and upper torso, pruritus)
Hepatotoxic, Ototoxic
24 HRS HELPLINE: 9891436206/9891334352
 DIAMS 67
2005 __________________________________PH A R M A C O ,OGY
INHIBITORS OF PROTEIN SYNTHESIS

TETRACYCLINES A M IN O G LY C O SID ES M A C R O LID ES CH LO RAM PH EN ICOL

Tetracycline Streptomycin CLINDAM YCIN
Erythromycin
Doxycycline Gentamycin Clarithromycin
Minocycline Amikacin Azithromycin
Demiclocycline N etilm ycin
Tobramycin

CHAIN ELONGATION TRANSLOCATION

1. AMINOGLYCOSIDES:
• Freeze initiation of protein
• Binds to 30S and Prevent polysome formation
• Misreading of m-RNA (Translation)

2. TETRACYCLINE:
• Binds to 30S and Prevents attachment of aminoacyl tRNA to A site.

3. CHLORAMPHENICOL
• Interferes with peptide bond formation
• Binds to 50S and Interfere with transfer of peptide chain from P—» A site

4. ERYTHRO/ CLINDAM YCIN

• Premature chain term ination
• Binds to 50S and Interfere with translocation of peptide chain back from A—»P site

Pneumonic “buy AT 30, CEL at 50”

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 DIAMS 68
2005_______________ PHARM ACOLOGY
TETRACYCLINES

Uses: Veneral diseases:

• Lymphogranuloma venerum (LGV)
• Granuloma inguinale
Brucellosis (Doxycycline + Rifampin)
Relapsing fever
Lyme disease
Rickettsial diseases
Plague prophylaxis
Cholera prophylaxis
Mycoplasmic infections (Atypical pneumonia) -^Second DOC to Erythromycin
Chlamydial infections (Trachoma, urethritis, pneumonia) —» Second DOC to Azithromycin
SIADH (Demiclocycline causes Diabetes insipidus)
Other uses: Pleurodesis, As an adjuvant in Malaria, Amoebiasis

A D R : Hepatotoxicity
Nephrotoxicity: Fancony syndrome (acute tubular acidosis)
Phototoxicity (highest with Demiclocycline)
Teeth & bone discoloration (permanent anterior dentition in children < 5 yrs)
Vestibular toxicity (highest with Minocycline)
Superinfection: Pseudomembranous colitis, Candidiasis

> Tetracycline are the M/C antibiotics to cause superinfection (Pseudomembranous colitis,
candidasis)
> Tetracyclines are contraindicted in hepatic failure ^yppalfailure, pregnancy, lactation and in
children < 8 yrs. ‘ \
> Doxycycline is only tetracycline, which can be safely given in renal failure.
> M/C mode o f developing resistance by gram-ve bacteria is a plasmid encoded active reflux
pump.

C H LO R A M PH EN IC O L

Uses: Active against Salmonella, H. influenza, meningitis

Primarily conjugated as glucuronide

A dr: Bone marrow suppression (idiosyncratic aplastic anaemia and dose related)
Gray baby syndrome
Resistance by acetyl transferase produced by bacteria

AM INOGLYCOSIDES
Uses:
> Streptomycin (first aminoglycoside to be discovered (Waksman)
• Used as Antitubercular drug
• DOC for Plague & Tularemia
> Amikacin- no cross-resistance, most potent against inactivating enzymes o f bacteria.
> Genta/Tobra/Amikacin are antipseudomonal drugs.
> Hepatic coma (Neomycin)

24 HRS HELPLINE: 9891436206/9891334352

 DIAMS 69
2005 PHARM ACOLOGY

ADR: Ototoxicity - Cochlear -progressive permanent deafness

Vestibular nausea, tinnitus, vertigo
Nephrotoxicity
Neurom uscular blockage: 4- Ach release (curare like reaction)
Increases myasthenic weakness

TOXICITY M O ST LEAST

OTOTOXIC Amikacin Netilmicin

VESTIBULOTOXIC Streptomycin Amikacin

NEPHROTOXIC Genta/Tobra Streptomycin

NEUROMUSCULAR Neomycin/Strepto Tobramycin

BLOKADE

N O TE : Penicillins and other cell wall inhibitors increase the uptake o f aminolycosides by a number o f
bacteria and enhance their transport (synergistic action) and thus decrease their toxicity.

tM A C R O L ID E S

Erythrom ycin (discovered by Me Gurfefjs. D O C for

• Atypical pneumonia (MycoplasmicJ ■»,
• Whooping cough
• Chancroid (one o f DOC as effective as Cotrimoxazole/Ceftriaxone)
• Campylobacter jejuni
Others: Chlamydial, prophylaxis for diphtheria,
ADR:
o GIT disturbance (due to binding o f erythromycin to motilin receptors)
o Cholestatic jaundice in pregnancy- Estolates
o Enzyme inhibition —> Rises the levels o f Theophylline, antiepileptics, Anticoagulants,
antihistaminics
o Torsades de pointes (Polymorphic ventricular arrythmia)- caused by
(Erythro/Clarithro/Ketoconazole/Itraconazole + Terfenadine/Astemizole/Cisapride)

Clarythro/A zithrom ycin are DO C for

• First line drugs in combination regimens for MAC in AIDS
• Legionnaire’s pneumonia
• Chlamydial infections (pneumonia, trachoma, nonspecific urethritis)
• Component of triple regimen for H. Pylori

24 HRS HELPLINE: 9891436206/9891334352

 DIAMS 70
2005 PHARM ACOLOGY
INHIBITION OF METABOLISM

PABA agonists: Sulfonamides

DHFRase inhibitors: Trimethoprim
Pyrimethamine
Methotrexate.

FOLATE METABOLISM

PABA -> FOLIC ACID THFA -> DNA; RNA

DHPSase DHFRase synthesis
A

Sulfonamide Trimethoprim, Pyrimethamine, Mtx

SULFONAMIDES

MOA: inhibition of bacterial folate synthetase.

Metabolism by acetylation and excreted by kidney.

Short acting Intermediate acting Long acting Special purpose

sulfonamides
Sulfadiazine Sulfamethoxazole Sulfadoxine Sulfacetamide
Sulfamethizole Sulfamoxole Sulfamethopyrazi ne Sulfasalazine
Mafenide

ADRi
• Crystalluria, hematuria
• Hypersensitivity- rash, drug fever, urticaria, SJ syndrome
• Hepatitis
• Hemolysis in G6PD deficiency
• Kernicterus in newborn.

USES:
. • UTI
• Chlamydial infections
• Nocardial infections
• Topical for bums (Silver Sulphadiazine, Mafenide)
• Ulcerative colitis, RA (Sulphasalazine)
• Toxoplasmosis (Sulphadiazine + Pyrimethamine)
• Malaria (Sulphadoxine + Pyrimethamine)

24 HRS HELPLINE: 9891436206/9891334352

 DIAMS
PHARM ACOLOGY
CQTRIM OXAZOLE
Sslphamethoxazole (SMZ) + Trimethoprim (TMP)
SMZ: TMP = 5:1 (oral) and 20:1 (Plasma)
Bactericidal
Sequencial block; synergistic.combination

Uses: DOC for PCP in AIDS

DOC for Chancroid (Other DOC: Erythromycin, Ceftriaxone)
UTI and respiratory tract infections
Traveller’s diarrhea
Prostatitis (Trimethoprim accumulates in prostate)

ADR: Megaloblastic anemia

Rash, Drug fever esp in AIDS
Teratogenic risk (antifolate)

INHIBITION OF DNA FUNCTION |

Fluroquinolones,
Metronidazole,
Rifampicin

. FLUROQUINOLONES

Inhibits DNA gyrase >

Digestion of DNA by endonucleases
Spectrum: Gram Negative Enterobactercea, Neiseria
No activity against obligate anaerobes
Antipseudomonal: Ciprofloxacin, Levofloxacin

ADR: CNS side effects - (insomnia, dizziness, convulsions)

Photosensitivity (Highest with Spar- and Pefloxacin)
Cartilage & tendon damage
Increases Theophyllin levels , |e s toxicity
Arrythmia (Sparfloxacin+ Terfenadine/Ketoconazole)

USES: UTI
Typhoid (DOC)
Gonorrhoea
Chancroid
Shigellosis
MDR TB

Contraindication: Pregnancy (teratogenic to fetus)

Children <17 yrs (because o f cartilage damage in developing joint)
Atheletes

24 HRS HELPLINE: 9891436206/9891334352

 DIAMS 72
2005 PHARM ACOLOGY
ANTIPSEUDOMONAL DRUGS
Penicillins C ephalosporins O th er p-lactum s
• Carbencillin Ceftazidime Imipenem
• Ticarcillin Cefoperazone Aztreonam
• Azlocillin Cefepime
• Mezlocillin
• Piperacillin
Quinolones
• Ciprofloxacin, Levofloxacin
Aminoglycosides
• Gentamycin, Tobramycin, Amikacin
Polypeptides
• Polymixin, Colistin

CHEMOPROPHYLAXIS
Meningococcal meningitis - Rifampicin
Hemophilus influenzae meningitis - Rifampicin
Plague - Tetracyline
Cholera - Tetracycline
Diptheria - Erythromycin
Pertusis - Erythromycin

DRUG OF CHOICE
• Streptococcal infections (Pharyngitis, Otitis media, Scarlet fever, SABE and RF) - Penicillin
• Staphylococcal infections - N afcillin, M cthicillinjT’enicillanase resistant)
Vancomycin (MRSA)
Quinupristin / Dalfopristin, Lirifezolid (VRE or VISA)
• Meningococcal infections - Penicillin (Penicillin sensitive)
Ceftriaxone - 3rd gen cephalosporins (Penicillin resistant)
• Gonococcal infections - Ceftriaxone OR Ciprofloxacin
• Hemophilus influenza infections - Ceftriaxone OR Co-trimoxazole
• Hemophilus Ducreyi (Chancroid) - Ceftriaxone, Azithromycin, Erythromycin, Ciprofloxacin
• Enteric fever - Ciprofloxacin OR Ceftriaxone {Typhoid carriers - Ampicillin)
• Mycoplama infections - Erythromycin
• Pertusis - Erythromycin
• Campylobacter infections - Erythromycin
• Leionella’s infections - Azithromycin
• Chlamydial infections - Azithromycin
• MAC in AIDS - Clarithro / Azithromycin
• PCP in AIDS - Co-trimoxazole
• Plague - Streptomycin
• Tularemia - Streptomycin
• Shigellosis - Quinolones
• Brucellosis - Doxycyclinc + Rifam pin OR Doxycycline + Aminoglycoside
• LGV - Doxycyline
• Donovaniasis - Doxycycline
• Syphilis, Yaws, Listeriosis, Anthrax, Actinomycosis - Penicillin (DO C)
24 HRS HELPLINE: 9891436206/9891334352
 DIAMS 73
2005 PHARM ACOLOGY
|1 ANTITUBERCULAR DRUGS 11

First line drugs Second line Drugs

Isoniazid (H) Amikacin, Newer drugs
Rifampicin (R) Kanamycin Ciprofloxacin
Pyrazinamide (Z) Ethionamide Ofloxacin
Ethambutol (E) Thiacetazone Clarithromycin
Streptomycin (S) Cycloserine Azithromycin
Capreomycin Rifabutin / Rifapin
PAS
ISONIAZID (INH)
Bactericidal
M O A : Inhibits mycolic acid synthesis
M etabolised in liver by acetylation (slow), Penetrates all body tissues, also CSF
ADR:
• Peripheral neuropathy —> Treated with PYRIDOXINE (Vit B6)
• Hepatitis
• Hemolysis in G6PD deficiency
• Neurological (mental disturbances, convulsions)
Used for treatment of TB along with other drugs
Used in chemoprophylaxis

RIFAMPICIN
Bactercidal, Resistance develops due to mutation o f rpoB gene
M O A : Inhibits DNA dependent RNA p,ol^merase & inhibits RNA synthesis
M etabolised in liver, excreted in bile, Peftbtrht&§ gll body tissues, also CSF
ADR:
• Red-orange discoloration of secretions and urine
• GI disturbance (M/C)
• Hepatitis
• Flu like syndrome
• Thrombocytopenic purpura
• POTENT MICROSOMAL ENZYME INDUCER: f effects of OCP, anticoagulants,
Hypoglycemics, Antivirals, Steroids, digoxin.
USES:
• Tuberculosis along with other agents
• Leprosy along with other agents
• Prophylaxis of Menningococcal and H.influenza and carrier state
• First line therapy of Brucellosis (Rifampicin + Doxycycline)
• Second/ third choice drug for MRS A, Staphylococcal endocarditis, along with other b-lactam s,

PYRAZINAMIDE
Bactericidal, MOA similar to INH, Most active in acidic pH
Good penetration to CSF
ADR: Hepatotoxicity
Hyperuricemia —>Arthralgia

24 HRS HELPLINE: 9891436206/9891334352

 DIAM S 74
2005 PH A R M A C O LO G Y
ETH A M BU TO L
BACTERIOSTATIC.
MOA: Inhibits nucleic acid synthesis (D-arabinose —>arabinogalacton)
Excreted in urine, distributed widely, but penetrates CSF incompletely
ADR:
• OPTIC NEURITIS, leading to loss o f visual acuity and red-green colour vision
(Not recommended for children < 6 yrs)
• Hyperuricemia
• Peripheral neuritis.

STREPTOM Y CIN
Bacteriocidal, aminoglycoside, Given by IM
Does not penetrate CSF
ADR:
Ototoxic (C/I in pregnancy —> causes perm anent deafness o f fetus)
Nephrotoxic

TREATM ENT
R ecom m ended dose of A TT
P (Pyrazinamide) 25 mg/kg (20-30)
E (Ethambutol) 15 mg/kg (15-20)
S (Streptomycin) 15 mg/kg (12-18)
R (Rifampicin) 10 mg/kg ( 8- 12)
I (Isoniazid) 5 mg/kg (4-6)

P opulation O f MTB '' A ctive D rugs

Rapidly growing with high bacillary load \ -► H
Slow growing intracellular bacilli (in m acrophages & inflamed sites) -> Z
Semidormant/persisters (within caseous material) -> R
Dormant -> NO DRUG

R N T C P guidelines
TB Category Initial phase Continuation phase
CATEGORY I
■ New smear positive 2HRZE 4HR
■ Seriously ill - sputum smear positive
■ Seriously ill - Extrapulmonary
CATEGORY H
■ Sputum smear positive- Relapse 2HRZES 5HRE
■ Sputum smear positive- Treatment failure
1HRZE
■ Sputum smear positive- Treatment after default
CATEGORY HI
■ Sputum smear negative-not seriously ill 2HRZ 4HR
■ Extrapulmonary- not seriously ill

24 HRS HELPLINE: 9891436206/9891334352

 DIAM S 75
2005 PHARMACOLOGY
TB in Pregnancy
• Avoid Streptomycin —> causes permanent deafness of fetus.
• HRZ and E are safe in pregnancy
• 2HRZ + 4HR —> safe regimen in pregnancy

TB in Liver disease
AntiTB Drugs Safe in Liver Disease
• STREPTOMYCIN
• ETHAMBUTOL
• RIFABUTIN
Avoid Pyrazinamide (Z) and Rifcimpicin (R) —> hepatotoxic

TB In Renal disease
AntiTB drugs safe in Renal failure
• RIFAMPICIN
• RIFABUTIN
Avoid Streptomycin (S) —>Nephrotoxic

TB in AIDS
> M.Tuberculosis —» 2HRZE + 7HR
> M. Avium complex (MAC)
• Prophylaxis in AIDS Clarithromycin / Azithromycin
• Regimen for T/t Clarithromycin / Azithromycin + Ethambutol Rifabutin

Indications of Steroids in TB
e Tuberculous meningitis, pericarditis, laryngitis
• Miliary Tuberculosis ^
• Pleural tuberculosis with pleural effusion
• Hypoadrenalism (absolute indication)
• Massive lymphadenopathy with pressure effects
• In AIDS with severe manifestations

Note: Steroids are C/I in INTESTINAL TB, silent perforation can occur.

24 HRS HELPLINE: 9891436206/9891334352

 DIAM S 76
2005 PHARM ACOLOGY

ANTILEPROTICS

DAPSONE
Structurally related to sulphonamides (Folate antagonist)
Metabolised in liver by acetylation, Concentrated in skin.
ADR:
• Gastric intolerance
• Hemolysis in G6PD deficiency
• Cutaneous reactions: fever, rash, pruritis, phototoxicity
• Methemoglobinemia
• Hepatitis
• Lepra reaction
• Agranulocytosis
USES:
• Leprosy
• PCP
• Dermatitis herpetiformis
• Chloroquine resistant malaria
• M adura foot

CLOF AZ AMINE
Dye, with leprostatic and anti-inflammatory effect.
Acummulates in tissues esp fat.
ADR: ^ v
• REDDISH BLACK discolouration o f skin and secretions^ "s
• Dryness o f skin, itching, Icthiosis
• GI intolerance

RIFAMPICIN
Most potent & Fastest acting bactericidal drug against mycobacterium leprae.
OTHER NEW DRUGS
MINOCYCLINE, OFLOXACIN, PEFLOXACIN, CLARITHROMYCIN, ETHIONAMIDE.

MULTIBACILLARY PAUCIBACILLARY
RIFAMPICIN 600 mg once a mth supervised 600 mg once a mth supervised
DAPSONE 100 mg daily self adm inistered 100 mg daily self administered
CLOFAZAMINE 300 mg once a mth supervised
50 mg daily self administered
Duration 24 mths 6 mths

R O M regim en
RIFAMPICIN 600 mg + OFLOXACIN 400 mg + M INOCYCLINE 100 mg is used for Single Skin
Lesion Without Nerve Involvement

DOC for Lepra reaction type I: STERIODS (Alternative: Clofazamine)

DOC for Lepra reaction type II: THALIDOMIDE (Alternative: Clofazamine, Steriods in severe cases

24 HRS HELPLINE: 9891436206/9891334352

 DIAM S 77
2005 PHARMACOLOGY
IfANTIFUNGALS II

Drugs for sysytemic mycosis

• Polyenes: Amphotericin B
• Pyrimidines: Flucytosine
• Azoles: Ketoconazole, Fluconazole, Itraconazole
Drugs for superficial infections
• Griseofulvin
• Terbinafine
• Azoles
Drugs for topical or local use
• Nystatin
• Miconazole
• Clotrimazole
• Tolnaftate

A M PH O T E R IC IN B
MOA: Bind to ERGOSTEROL present in fungal m em brane—> ARTIFICIAL PORES —» f cell
membrane permeability —> leakage of intracellular com ponents —> leads to cell death.
Used I/V or Intrathecally.
Metabolised in liver
USES: Most Imp drug for systemic mycosis.
' • DOC for Aspergillosis, Mucormycosis, Cryptococcus, Extracutaneous Sporothricosis
disseminated Candiasis
Blastomycosis, Histoplasmosis) (^<(:(d^odomycosis,Paracoccidiodomycosi:
(Rapidly progressive or involving CN§)X ^
Leishmaniasis (in resistant cases and M ucocutaneous forms)
ADR:
• Acute reaction:- Anaphylactic shock, chills, rash, dyspnea,tachycardia
• Nephrotoxicity:- Azotemia, acidosis, hypokalemia, decrease GFR
• Anemia, Thrombocytopenia
• CNS toxicity-.- Headache, arachnoiditis, convulsions

New formulations o f Amphotericin B

a) Am photericin B lipid complex (ABLC)
b) Am photericin B colloidal dispersion (ABCD)
c) Liposom al Amphotericin B
They produce milder acute reaction, lower nephrotoxicity, minimal anemia

FLU CY TOSIN E (5-FC)

Related to 5-FU (antimetabolite)
Good penetration to CSF
MOA: Inhibits THYM IDYLATE SYNTHASE which is used for nucleic acid synthesis
Used in combination w ith Amphotericin B for Cryptococcus, Candida, Chromoblastomycosis.

24 HRS HELPLINE: 9891436206/9891334352

 DIAMS 78
2005 PHARMACOLOGY
AZOLES
MOA: Inhibit conversion of LANOSTEROL -»• ERG O STERO L

Ketoconazole
Poorly absorbed from GIT, CSF penetration poor
ADR:
• Gynecomastia, menstrual irregularities, j, libido and potential (Inhibits steroid biosynthesis)
• Hepatitis
• Teratogenicity (C/I in Pregnancy)
• P450 cytochrome Enzyme Inhibitor (increase blood levels o f anticoagulants, anticonvulsants,
steroids, hypoglycemics)
• Torsades-De-Pointes (Ventricular arrhythmia) w hen given terfenadine, astemizole, cisapride
USES:
• Chronic Mucocutaneous Candidiasis
• Dermatophytosis (griseofulvin resistant)
• Cushing’s disease (inhibits steroid synthesis)
• Precocious puberty in boys (inhibits testosterone syntheis)

Fluconazole
Good penetration in CSF, preferred drug in Fungal m eningitis.
Oral and I/V
USES:
• DOC for Esophageal and Oropharyngeal Candidiasis
• Cryptococcal / Coccidioidal Meningitis in immunocompromised

Itraconazole
USES:
® DOC for Chromomycosis, Paracoccidioidomycosis
• Non-meningeal (not involving CNS) Histoplasmosis, Blastomycosis
• Cutaneous Sporotrichosis
• Aspergillosis (alternative to AMB)
• Also used for Dermatophytosis, Onychomycosis

GRISEOFULVIN
Fungistatic, (Topically NOT effective)
Ultramicrosize formulations —»• better absorbed
Absorption aided by high fa t diet & by microfining the drug particles.
Gets distributed to stratum comeum —* binds to keratin
MOA: Interferes with microtubule function o f mitotic spindle (but does not cause metaphase arrest)
USES: Restricted to DERMATOPHYTOSIS, skin, hair, nail
(NOT effective against CANDIDA and TINEA VERSICOLOR)
ADR: Headache, confusion, Photosensitivity, Disulfiram like reaction

TERBINAFINE
Fungicidal
MOA: Inhibits'enzyme ‘SQUALENE EPOXIDE’
USE: More effective than Griseofulvin for Dermatophytosis, including Onychomycosis
ADR: GI upset, taste disturbance.
24 HRS HELPLINE: 9891436206/9891334352
 DIAMS 79
2005 PHARMACOLOGY

DISEASE DOC

CANDIDIASIS
Oralpharyngeal / vaginal / cutaneous F L U /N Y S
Disseminated AMB

CRYPTOCOCCUS AMB ± 5-FC / FLU

ASPERGILLOSIS AMB

MUCORMYCOSIS AMB

HISTOPLASMOSIS
Rapidly progressive or Disseminated or CNS AMB
Non CNS ITR

BLASTOMYCOSIS
Rapidly progressive or Disseminated or CNS AMB
Non CNS, indolent ITR

COCCIDIOMYCOSIS
Rapidly progressive or Disseminated AMB
Meningeal FLU / AMB

CHROMOMYCOSIS ITR

P a r a c o c c id io id o m y c o s is ITR

24 HRS HELPLINE: 9891436206/9891334352

 DIAMS 80
2005 PH A R M A C O L O G Y
ANTIMALARIALS

gs?®
| Female mosquito picks
g§ Infected mosquito rugs citcetive against up gamecocytes from
injects sporozoites 'coerythrocytic from: the infected individual

Blood
contaminated
neddle
§| Rupture of RBC
releases merozoites
which can infect other
red hlood cells
Dams eifectivc aizainst
\tic form
ErythrocytjcTprrh
CHLOROQ (JIN E
QUININEf-’ ' '
M EFLO ^^^;
» PYRtMETFIAMINJEl

A. Blood Schizonticides (Act on erythrocytic stage of schizogony in blood)

Fast acting Intermediate acting Slow acting
Chloroquine Mefloquine Proguanil
Artemether (fastest) Quinine Pyrimethamine
Halofanthrine Sulfonamides
Tetracyclines
B. Tissue schizonticides (Act on Preerythrocytic or exoerythrocytic stages in liver)
Primaquine —> Preerythrocytic & Exoerythrocytic
Proguanil —> Preerythrocytic
Pyrimethamine —> Exoerythrocytic
Tetracyclines —>• Preerythrocytic

C. Gametocides (Kill gametocytes in blood)

Primaquine, Artemisinin --> Kill Falciparum gametocytes
Primaquine, Artemisinin, Chloroquine, Quinine —>Kill Vivax gametocytes

D. Sporontocides (Do not kill gametocytes but render them non-infective in the mosquito)
Pyrimethamine, Proguanil

24 HRS HELPLINE: 9891436206/9891334352

 ANTIVIRAL DRUGS

ANTI-HERPES VIRUS AGENTS J

Acyclovir
Convened to Acyclovir triphosphate —> inhibits viral DNA-polymerase.
USES:
• Herpes Simplex virus (H SY ) infection (Genital herpes, Severe herpetic gingivostomatitis,
„ HSV encephalitis. Mucocutaneous HSV, Herpetic keratoconjunctivitis)
« Chicken pox
« Herpes zoster in immunodeficient hosts.
ADR:
Renal toxicity
Neurological (tremors, delirium , seizures, hallucinations)

Ganciclovir .
Inhibits DNA-polymerase o f CM Y & HSV.
DOC for CMV retinitis in AIDS
ADR: Severe neutropenia, thrombocytopenia, anemia. (Myelotoxicity when given with Zidovudine !

.-'esearnet
nnihit? DNA-polymerase and Reverse transcriptase
■p
'■ Acs: a C.’MV retinitis.in AIDS, as an alternative to wgancyclovir
; c Acyclovir resistant H erpes infection.

. aesuridinc, T rifluridine X
Topically used in Herpetic keratoconjunctivitis. % «' %

Samciclovir, Penciclovir
, sod in Localised Herpes Zoster (as an alternative to acyclovir)
Chronic Hepatitis B (as an alternative to Lamivudine)

ANTIRETROVIRALS AGENTS [j

.: Nuc eoside Reverse transcriptase 2) Non-nucleoside RTI 3) Protease inhibitors 4 }Nucleotide

inhibitors (NRTI) . analogs
Zidovudine Nevaripine Indinavir Tenofovir
Didanosine Delaviridine R itonavir Adenofovir
Stavudine Efavirenz Saquinavir
Zalcitabine N elfinavir
Lantuvudine Amprenavir
Abacavir

5i Fusion Inhibitor —> Enfuviritide

\'O TE Initiate IIAART when

CD4 < 200/p.l
Viral load i.e. HIV-RNA level > 50,000 by PCR
Zidovudine
Inhibit? viral jreverse transcriptase (RNA dependent DNA polymerase) o f HIV 1 & HIV 2
USES: Used in combinations for t/t o f H IV
Prophylaxis o f needleprick injuries
Prophylaxis for vertical transm ission to neonate in pregnant HIV +ve women
ADR: Anemia, Neutropenia, Myopathy

D idanosinc, Stavudine, Zalcitabine

ADR: Peripheral neuropathy
pancreatitias.

Lam ivudinc
Least toxic among NRTIs
Does NOT cause Peripheral neuropathy and Pancreatitis
Most effective in chronic Hepaitis B

PROTEASE INHIBITORS
Mo*t significant adr effect is LIPODYSTROPY SYNDROME
Oi'nei aui Gi uiMuiuances, Hyperglycemia, nephrolithiasis (indinavir)

A NTHNFLUENZA VIRUS AGENTS ‘

.Amantadine
inhibits adsorption, penetration and uncoating
i )OC for prophylaxis and treatment in INFLUENZA TYPE A
Also as an ANTIPARKINSONISM DRUG (Dopamine facilitator)
ADR: Ankle edema .
^ Av
’ ••pi.
Neurological (Nightmares, Hallucinations, Insomnia)
Cardiac arrhythmia, Livedo reticularis

N QN-SELECTIVE ANTIVIRAL DRUGS

R ibavarin
l !scd in aerosol form for RESPIRATORY SYNCITIAL VIRUS bronchiolitis in infants and children
Also used in Influenza and measles

Interferons
Host specific, not virus specific
E R a —> produced by leukocytes A
ini' Ji -* produced by fibroblasts
in f y produced by immune cells (lymphocytes)

USES: ’
Chronic hepatitis B & C
AIDS related Kaposi Sarcoma
i iairy cell leukemia
Condyloma acuminata
 ! DIAMS 81
m l5 PHARM ACOLOGY
m fE :-
j» Blood Schizonticides are used for SUPPRESSIVE PROPHYLAXIS and for acute attack i.e.
i they produce CLINICAL CURE in P. Vivax & P.Ovale, P.Falciparum and RADICAL CURE
in P.Falciparum (no exoerythrocytic stage)
• Tissue schizonticides are used for RADICAL CURE in P.Vivax & P.Ovale i.e. to prevent
relapses (exoerythrocytic stage) and also for CASUAL PROPHYLAXIS (Preerythrocytic
stage) i.e. prevent the invasion o f erythrocytes and further clinical attacks.
• Gametocides & Sporontocides are used for preventing transmission o f m alaria to mosquito

CHLOROQUINE
Blood schizonticide & Gametocidal to vivax
M O A : Inhibits digestion of hemoglobin by the parasites
l DNA synthesis of parasite
A D R: GI irritation
Visual disturbances (Retinopathy, Corneal deposits, Bull’s eye maculopathy)
Pruritus & dermatitis, lichenoid eruptions
Myopathy
Intravenous route:- CVS - Hypotension, arrhythmia, ECG abnormalties
CNS - Convulsions in children, Mental disturbances
DOC for Malaria in PREGNANCY
Other uses:
• Extraintestinal amebiasis
• Rheumatoid arthritis
1 • Discoid lupus erythmatosus
• Lepra reaction
® Photogenic reactions \ x
• Porphyria cutanea tarda v '■
• Infectious mononucleosis

QUININE
Blood Schizonticide & Gametocidal to vivax
USES:
• DOC for Severe forms o f chloroquine resistant or mulitidrug reisitant falciparum malaria
• DOC in cerebral malaria
• Used in nocturnal leg cramps
• Babesiosis —>Quinine + Clindamycin
ADR: Cinchonism - tinnitus, high tone hearing loss, disturbed color vision, GI irritation, Syncope
Hypoglycemia
Hemolysis in G6PD deficiency —>Black water fever
QT prolongation

MEFLOQUINE
DOC for quinine resistant falcifarum malaria.
Prophylactic agent o f choice for chloroquine resistant Falciparum and other strains.
ADR: Neuropsychiatric (psychosis, hallucinations, depression, seizures)

PRIMAQUINE
Tissue schizonticide (Preerythrocytic and Exoerythrocytic) & Gametocide
24 HRS HELPLINE: 9891436206/9891334352
 DIAMS 82
2005 PHARMACOLOGY
DOC for radical cure of P.Vivax and P.Ovale
ADR: GI distress, Hemolysis in G6PD deficiency, Methemoglobinemia.

ANTIFOLATE DRUGS
Pyrimethamine + Sulphadoxine (Fansidar)
Used for chloroquine resistant strains.

ARTEMISININ, ARTEMETHER
Newer agents with wider stage specificity
Uses: Chloroquine resistant strains
Acute attacks of severe falciparum m alaria including Cerebral malaria.
ADR: Reticulopenia, drug fever, allergy.

PROGUANIL
Slow acting erythrocytic schizontici.de, Preerythrocytic tissue schizonticide.
Use is restricted to prophylaxis of chloroquine resistant falciparum

ANTIBIOTICS USEFUL IN MALARIA

Sulphonamides (Sulphadoxine, Sulphadiazine, Dapsone)
Doxycycline,
Azithromycin,
Clindamycin

AT OVAQU ONE
Newer agent (Blood schizonticide for Falciparum)
Second line choice for P. Carinii & T.Gondii 5
\l\ A.
'N $ \
C asual Prophylaxis
a) Proguanil
b) Primaquine
Suppressive Prophylaxis
i) Chloroquine sensitive P.Vivax, P.Ovale, P.Malariae & P.Falciparum :- CHLOROQUINE
ii) Chloroquine resistant P.falciparum :- MEFLOQUINE / PROGUANIL / DOXYCYCLINE

Treatment
i) Chloroquine sensitive P.Vivax, P.Ovale, P.Malariae & P.Falciparum
a) Clinical cure :- CHLOROQUINE
b) Radical cure :- P.Vivax, P.Ovale —> PRIMAQUINE
P.Falciparum —>No further t/t required (No exoerythrocytic stage)

ii) Chloroquine resistant P.Falciparum or Multidrug resistant strains and other severe malaria
One of the following regimens can be used:-

a) QUININE ALONE or QUININE + FANSIDAR or QUININE + TETRACYCLINE

b) ARTESUNATE / ARTEETHER7 ARTEMISININ
c) MEFLOQUINE
d) HALOFANTHRINE
e) ATOVAQUONE AND PROGUANIL

24 HRS HELPLINE: 9891436206/9891334352

 DIAMS 83
2005 PHARMACOLOGY

ANTIAMOEBIC DRUGS & ANTIPROTOZOAL DRUGS

1. Tissue amoebicides
a) For both intestinal and extraintestinal amoebiasis
• M etronidazole, Tinidazole, Secnidazole
• Emetine, Dehydroemetine

b) For extraintestinal amoebiasis only

Chloroquine

2. Luminal amoebicides
• Diloxanide furoate
• Iodoquinol, Quiniodochlor
• Tetracyclines, Parmomycin

Metronidazole
MOA: inhibit DNA synthesis
USES:
• First line drug for all forms of amoebic infection (mild to severe intestinal amoebiasis and also
in extraintestinal amoebiasis)
• DOC for TRICHOMONIASIS, GIARDIASIS, PSUEDOMEMBRANOUS COLITIS
• DOC for GUINEA WORM INFESTATION

24 HRS HELPLINE: 9891436206/9891334352

 DIAM S 84
2005 PHARMACOLOGY
• Anaerobic bacterial infections
• H.pylori infection
• Ulcerative gingivitis
ADR: M etallic taste, GI disturbance, Leukopenia
Disulfiram like reaction with alchohol.

Emetine
ADR: Cardiovascular toxicity, Muscle weakness. (Seldom used)

Diloxanide furoate
Luminal amoebicide, kills trophozoites responsible for the production of cysts.
DOC for asymptomatic (carrier) amoebiasis
ADR: Flatulence (M/C)

Treatment of amoebiasis
Asymptomatic (carrier) intestinal amoebiasis —» DILOXANIDE FUROATE
Mild to severe intestinal amoebiasis —> METRONIDAZOLE ± DILOXANIDE FUROATE
Extraintestinal (Hepatic) amoebiasis —> METRONIDAZOLE ± CHLOROQUINE

DRUGS FOR GIARDIASIS

DOC for Giardiasis METRONIDAZOLE

DRUGS FOR TRICHOMONIASIS

DOC for Trichomoniasis —► METRONIDAZOLE

DRUGS FOR LESHMANIASIS - \

DOC for Leshmaniasis (Kala Azar) —►Sodium stibogluconate (Pentavalent antimony)•

• Antimonials: Sodium Stibogluconate, M eglumine antimonite

• Diamidine : Pentamidine
• Others: Amphotericin, Ketoconazole, Allopurinol, Miltefosine

DRUGS FOR TRYPANOSOMIASIS

a) African Trypanosomiasis (Sleeping sickness)

i) DOC for early hemolymphatic stage —> SURAMIN
ii) DOC for late meningoencephalitic stage —» MELARSOPROL

b) American Trypanosomiasis (Cbaga’s disease) —» NIFURTIMOX.

DRUGS FOR TOXOPLASMOSIS

DOC for Toxoplasmosis -> SULPHADIAZINE + PYRIMETHAMINE
DOC for Toxoplasmosis in Pregnancy —> SPIRAMYCIN

24 HRS HELPLINE: 9891436206/9891334352

 I ANTIHISTAMI.NI.CS |
i
..
'• - -------------- :~ --------------------^

First gcueralian anlihistam inies

• Highly sedative: Promethazine, Diphenhydramine, Dimenhydrinate

* Moderately sedative: Pheniramine. Cyproheptadine, M eclizine, Cinnarizine

« Mild sedative: Chlorpheniramine, Cyclizine, Clemastine

Second generation anlihistaminies (Non-sedative): Terfinadiue, Fexofenadine. Astemizole

Loratidine, Cetrizine, Azelastine

Actions:
1st generation: Anlihislamintc, Antiallergic, Anticholinergic, am i Sedative (cross BBB)
2nd generation: Antihistaminic. Antiallergic (NO anticholinergic, NO sedative action)

T crl’in adine
Most rapid onset
Adr: Torsades de pointes (polymorphic ventricular arrvhthmia) when given with
Frythromycin ■Clarithromycin / Ketoeonazole / Itraconazole
(Note: Azithrom ycin <T Fluconazole are safe)

Fexofenadine: Active metabolite of terfinadine, does not cause cardiac arrhythmia

Astemizole: 1.ongc.st dura lion o f action. It causes cardiac arrhythmia like terfinadine

Loratidine: Lacks CNS depression eftehts'fN^edation)

Cetrizine: Not metabolized

Azelastine: Best topical activity

USES:
• Allergic disorders (itching, urticaria, seasonal rhinitis, angioedenia, atopic dermatitis,
anaphylaxis)
• Idiopathic pruritides (DOC)
• Common cold
• Motion sickness (Promethazine, diphenhydramine, cyclizine)
• Vertigo (Cinnarizine)
• Parkinsonism (Promethazine)
• Preanacslhotie medication, as sedative (Promethazine)
« As sedative, hypnotic, anxiolytic

SHF ‘‘Drugs lor peptic ulcer"

 ANTIHELMINTICS ||

DRUGS M OA
Albendazole, Mebendazole, Thiabendazole l glucose uptake & loss o f intracellular microtubules
Pyrental pamoate Spastic paralysis
Piperazine Flaccid paralysis
Ivermectin Tonic Paralysis (Stimulate release of GABA)
Levamisole Tonic paralysis ■
Praziquantel Contracture & Paralysis
Diethyl carbamazine (DEC) Promotes phagocytosis o f worms.

SAFE in pregnancy —» Piperazine, Pyrantel pamoate, Niclosamide

C/I in pregnancy —» Albendazole, Mebendazole, Thiabendazole.

DRUGS FOR NEM ATODES

• Ascaris lumbricoides -» ALBENDAZOLE / M EBENDAZOLE / PYRANTEL
• Enterobius vermicularis —>MEBENDAZOLE / PYRANTEL / ALBENDAZOLE
• Necator Americans / Ankylostoma duodenale —>MEBENDAZOLE
• Trichuris trichura —►MEBENDAZOLE
• Trichinella spirallis —» ALBENDAZOLE
• Strongyloides stercoralis —> IVERMECTIN
• Wucheria bancrofti —> DEC
T • W .loaloa -> DEC . :
• Oncocera volvulus —»■IVERMECTIN
• Drancunculus m edinensis —^ 'METRONIDAZOLE
• Cutaneous larva migrans —>■ Tl'lIA iN DAZ OI.E / IVERMECTIN
• Visceral larva m igrans —> STERIODS

DRUGS FOR TREM ATODES

• Schistosomes —» PRAZIQUANTEL
• Paragonimus westermani —> PRAZIQUANTEL
• Fasciola hepatica —» TRICLABENDAZOLE; BITHINOL

DRUGS FOR C E ST O D E S
® Taenia solium, Taenia Saginata, D.Latum, H.Nana —» PRAZIQUANTEL
• ' Neurocysticercosis —> ALBENDAZOLE
• Echinococcus (Hydatid disease) —> PAIR treatment + ALBENDAZOLE
(Percutaneous needle Aspiration, Injection of scolicidal
' agent & Reaspiration) •
 DIAMS 86
2005 PHARMACOLOGY

ANTICANCER DRUGS |

1. ALKYLATING D R U G S
• Nitrogen mustards'. - Cyclophosphamide, Ifosfamide, Chlorambucil, Melphalan
• Nitrosureas: - Streptozocin, Carmustine, Lomustine
• Busulfan
• Dacarbazine
• Thio-TEPA

2. A N TIM ETA B O LITES

1. Folate antagonists
• Methotrexate
2. Purine antagonists
• Mercaptopurine
• Azathiaprine
• Fludarabine, Cladribine, Pentostatin
3. Pyrimidine antagonists
• 5-Fluorouracil (5-FU)
• Cytarabine (Cytosine arabinoside)
• Gemcitabine

3. VINCA ALKALOIDS
Vincristine (Oncovin)
Vinblastine

4. ANTIMALIGNANT ANTIBIOTICS
Anthracyclines: - Daunorubicin, Doxorubicin (Adriamycin) l
Others: Bleomycin, M itom ycin C, Actinomycin D, Plicamycin (Mithramycin)

5. OTHERS
Topoisomerae I inhibitors: Topotecan, Irinotecan
Topoisomerae II inhibitor: Etoposide
Taxenes: Paclitaxel
Miscellaneous: Hydroxyurea, Cisplatin, Procarbazine, L-asparginase

6. HORMONES
Glucocorticoids (Prednisolone)
Progestins
Estrogens
Antiestrogens (Tamoxifen)
Antiandrogen (Flutamide)
5a reductase inhibitor (Finasteride)
GnRH analogues (Buserelin, Naferelin, Leuprolide)
Somatostatin analogue (Octreotide)

24 HRS HELPLINE: 9891436206/9891334352

 DIAMS 87
2005 PHARMACOLOGY

a) Cell-cycle nonspecific d ru g s (Kill only resting and multiplying cells)

• Alkylating drugs
• Antibiotics
b) Cell-cycle specific d ru g s (Kill only actively dividing cells)
These drugs show phase selectivity
• G1 phase: Synthesis o f components for DNA sysnthesis - e.g. VINBLASTINE
• Sphase : DNA synthesis - e.g. ANTIMETABOLITES
• G2 phase: Synthesis o f components for mitosis - e.g. BLEOMYCIN, ETOPOSIDE
• Mphase : Mitosis - e.g. VINCA ALKALOIDS
• GOphase: Non-proliferative phase (resting phase)

ALKYLATING DRUGS
Cyclophosphamide
ADR: -Acute sterile Hemorrhagic cystitis (Due to metabolite ‘A crolein’)
(Treated with M ESNA and vigorous hydration)
-Bone marrow supression
-Alopecia
-Cardiotoxic
-Sterility, amenorrhea
Busulfan
ADR: Pulmonary fibrosis
Hyperuricemia
* Thrombocytopenia
Sterility, alopecia
DOC for Chronic Myeloid Leukemia '((CML).

Nitrosureas
Lomustine, Carmustine—» Crosses BBB, So used in Meningeal leukemias and brain tumours
Streptozocin —>DOC for Insulinoma

Melphalan: DOC for M ultiple myeloma

Chlorambucil: DOC for Chronic Lymphocytic leukemia

Dacarbazine: DOC for m alignant melanoma. Also used in H odgkin’s disease.

ANTIMETABOLITES
Methotrexate
MOA: Inhibits DHFRase
ADR: Bone marrow suppression —» Leucovorin(Folinic acid) rescue
Hepatotoxicity
Pulmonary fibrosis
Leucoencephalopathy (with intrathecal adrnn)
USES: Breast cancer
Choriocarcinoma
Rheumatoid arthritis
Severe psoriasis

24 HRS HELPLINE: 9891436206/9891334352

 DIAMS 88
2005 PHARMACOLOGY
Immunosupressant
Osteogenic sarcoma
Ectopic pregnancy
Part of combination therapy in ALL & Burkitt’s lymphoma

Mercarptopurine
Metabolism by XANTHINE OXIDASE
So inhibited by Allopurinol (te s toxicity)

Fludarabine:
Effective in CML, low grade lymphomas,
DOC for W aldenstorm’s macroglobulinemia

Cladribine: DOC for Hairy cell leukemia

Pentostatin
Inhibitor of enzyme adenosine deaminase
Second line DOC for Hairy cell leukemia.

5-Fluorouracil
Inhibits ‘Thymidylate synthase’ synthesis & leads to ‘thymineless death’ o f cells
ADR: Bone marrow suppression
Mucositis
Cardiotoxic (chest pain, MI)
Hand & foot syndrome

Cytarabine (Cytosine arabinoside)

MOA: Inhibits DNA polym erase -IS. >

Mainly used in ALL in children

Also used in Hodgkin and Non-hodgkin’s lymphoma

Gemcitabine: DOC for Pancreatic Cancer

VINCA ALKALOIDS
Vincristine
MOA: Inhibits microtubule assembly & hence disruption of m itotic spindle (Metaphase arrest occurs)
ADR: Peripheral neuritis
Alopecia

ANTIMALIGNANT ANTIBIOTICS
Doxorubicin (Adriamycin), Daunorubicin
MOA: Blocks DNA/RNA synthesis (Topoisomerase II inhibitors)
Generates hydroxyl free radicals which are highly cytotoxic.

ADR: Cardiotoxicity (Arrythmias, pericarditis, myocarditis, fatal CCF)

Bone marrow suppression
Severe alopecia, Stomatitis
Radiation recall reactions
Amifostine & Dexrazoxane (iron chelator) reduce cardiotoxicity.

24 HRS HELPLINE: 9891436206/9891334352

 DIAMS 89
2005 PHARM ACOLOGY

Bleomycin
ADR: Non-ishaemic chest like pain
Pulmonary fibrosis
Mucocutaneous toxicity (hyperpigmentation, ulceration, Skin rash, alopecia)
Raynaud’s phenomenon

Plicamycin: Used for treatment o f hypercalcemia associated with malignancy.

OTHERS
Topotecan, Irinotecan: Topoisomerase I inhibitors
Etoposide: Topoisomerase II inhibitor

Hydroxyurea:
DOC for CML.
DOC for Polycytemia vera.

Cisplatin
ADR: Vomiting (Most highly emetic anticancer drug)
Nephrotoxicity
Ototoxicity (tinnitus, deafness)
Hyperuricemia

•Procarbazine : MAO inhibitor, ADR: Disulfiram like reaction with alchohol

HORMONES x .
Steroids: Lymphocytic leukemia, I .ymph'ontivTIreast Ca
Antiandrogen (Flutamide): Prostate Ca
Estrogens: Prostate Ca, Male Breast ca
Antiestrogens (Tamoxifen): Breast Ca
Progestins: Endometrial Ca
Finasteride: Prostate Ca
GnRH analogues
• Leuprolide: Breast Ca
• Busereli: Prostate Ca
Octreotide: Carcinoid tumours, VIP secreting tumours,

CHEMOPREVENTION
Tamoxifen Breast Ca
Finasteride Prostate Ca

Isotretnoin
V itE U pper Aerodigestive tract including Ca lung &
Selenium prem alignant conditions (Leukoplakia)

NS AIDS -* Colon Ca
Calcium
Hepatitis-B vaccine —» Hepatomas

24 HRS HELPLINE: 9891436206/9891334352

 DIAMS 90
PHARM ACOLOGY

| TOXICITY AMELIORATION (DETOXICATION)

• Folinic acid rescue
• Mesna & acetylcysteine
• Ondansetron (antiemetic)
• Allopurinol
• Steroids
• Plicamycin
• Biphosphonates
• Calcitonin
• Lithium
• Amifostine & Dexrazoxane
• Biological response modifiers (recombinant GM-CSF / G-CSF)
• Platelet and or / granulocyte transfusion

DRUG OF CHOICE
a) Acute lymphatic leukemia (ALL)
. Induction: VINCRISTINE + PREDNISOLONE + ASPARGINASE ± DOXORUBICIN
• CNS prophylaxis: INTRATHECAL METHROTREXATE

b) Acute myelogenous leukem ia (AML): CYTARABINE ± DOXORUBICIN

c) Acute promyelocytic leukem ia (AML-M3): ALL TRANS RETINOIC ACID
d) Chronic lymphocytic lym phom a (CLL): CHLORAMBUCIL
e) Chronic myelogenous leukem ia (CML): INTERFERON A (DOC), HYDROXYUREA,
BUSULFAt'K
f) Hodgkin’s lymphoma: (ABVD) ADRIAMYCIN + BLEOMYCIN + VINBLASTINE +
DACARBAZINE
g) Non-hodgkin’s lymphoma:
• Diffhse large cell lymphoma: (CHOP) CYCLOPHOSPHAMIDE + DOXORUBICIN +
VINCRISTINE (ONCOVIN) + PREDNISONE
• Burkitt’s lymphoma: CYCLOPHOSPHAMIDE + VINCRISTINE + METHOTREXATE
h) Hairy cell leukemia: CLADRIBINE
i) Waldenstorm’s macroglobulinemia: FLUDARABINE
j) Breast Ca: (CMF) CYCLOPHOSPHAMIDE + METHOTREXATE + 5-FLUOROURACIL
k) Pancreatic Ca: GEMCITABINE
l) Adrenal Ca: MITOTANE
m) Thyroid Ca: RADIOIODINE I 131
n) Polycytemia vera: HYDROXYUREA
o) Choriocarcinoma: HYDROXYUREA
p) Multiple myeloma: M ELPHALAN or CYCLOPHOSPHAMIDE
q) Cancer Urinary bladder
• Local: Instillation o f BCG or DOXORUBICIN
• Systemic: (MVAC) METHOTREXATE + VINBLASTINE + DOXORUBICIN + CISPLATIN

24 HRS HELPLINE: 9891436206/9891334352

 DIAMS 91
PHARM A C O L O G Y
i
1
IIMMUNOPHARMACOLOGY |

IM M U N O SU PPR ESSA N TS^

1. Specific T-cell inhibitors ( Calcineurin inhibitors)

• Cyclosporine, Tacrolimus
2. Cytotoxic drugs (Antiproliferative drugs)
• Methotrexate, Cyclophosphamide, Azathioprine
3. Glucocorticoids
• Prednisolone
4. Antibodies
• Muromonab CD3, Antithymocyte globulin (ATG)
Rho (D) immunoglobin

T-cells as well as expression o f IL-2 and other cytokines by them

2. Cytotoxic drugs - Block proliferation and differentiation of T and B cells
3. Glucocorticoids - Inhibit MHC expression and 11-1, IL2, IL6 production so that helper T cells
are not activated
4. Antibodies like Muromonab CD3, ATG - Specifically bind to Helper T cells, prevent their
response and deplete them
24 HRS HELPLINE: 9891436206/9891334352
 DIAMS 92
2005 PHARM ACOLOGY
Cyclosporine
MOA: Binds to ‘cyclophillin’ —> inhibits Calcineurin, which is responsible for production o f cytokines
Inhibits synthesis o f IL-2 & antigen activated stimulation & proliferation o f helper T-cells
ADR: Nephrotoxic
Hirsutism
Cholelithiasis
Osteoporosis
Myopathy
USES: Most effective drug for prevention and treatment o f graft rejection (renal, hepatic, cardiac, bone
marrow)

Tacrolimus
• MOA: same as cyclosporine
• Adr: Nephrotoxicity, neurotoxicity, alopecia

Muromonab CD3
Monoclonal antibody against CD3 antigen on T-helper cells —►obstruction o f binding o f MHC-II
antigen to the T-cell receptor —> prevention o f participation o f T-cells in the immune response

Antithymocyte globulin (ATG)

• Polyclonal antibody against T-cells and depletes them

Anti-D immunoglobulin
• Human IgG antibody against Rh (D) antigen
• Used for Rh hemolytic disease

IM M U N O M O D U LA TO RSl ^V\

• Levamisole
• Aldeslukin
• BCG
• Filfrastim (G-CSF), Sargramostim (GM-CSF)
• Interferons
• Thymosin

Levamisole:
An antiparasitic drug
Uses: Nephrotic syndrome, HD, RA

BCG: Intravesical chemotherapy in superficial Urinary bladder Ca

G-CSF/GM-CSF: Biological response modifiers, Hastens recovery o f neutrophil count

Thymosin:
Protein hormone from thymus
Used in DiGeorge’s syndrome (Thymic aplasia)

24 HRS HELPLINE: 9891436206/9891334352

 DIAM S 93
2005 PHARMACOLOGY

IICHELATING AGENTS

1. DIMERCAPROL (BAL)
• Mainly used for As, Hg poisoning
• Also used in Au, BI, Ni, Sb
• C/l in Iron & Cadmium poisoning

2. CALCIUM DISODIUM EDTA (Ca N a2EDTA)

• DOC for Lead poisoning

3. PENICILLAMINE
• Copper poisoning & W ilson’s disease
• Mercury poisoning (As an alternative to Dimercaprol)
• Lead poisoning (As an adjuvant to CaNa2EDTA)
• Cystinuria & Cystine stones
• Scleroderma

ADR: Lupus like syndrome

Nephrotoxicity
Aplastic anemia
Myopathy

* 4. DESFERRIOXAMINE
• DOC for iron poisoning
• Also used in transfusion sidferpMs:
• Administered parenterally (i/m j'vVXX

5. DEFERIPRONE
• Orally active iron chelator

24 HRS HELPLINE: 9891436206/9891334352

 DIAMS 94
2005 PHARM ACOLOGY
l CLINICAL MANIFESTATIONS OF ADVERSE REACTIONS TO DRUGS 1

DRUGS CAUSING LUPUS LIKE SYNDROME

Procainamide Isoniazid
Phenytoin Hydralazine
Procarbazine Methyldopa
Phenolpthalein

DRUGS CAUSING DISULFIRAM LIKE REACTION

Cephalosporins (Cefamandole, Cefoperazone, Cefofetan)
Chlorpropramide
Metronidazole
Furazolidone
Griseofulvin

DRUGS CAUSING GYNECOMASTIA

Spironolactone Estrogens & testosterone
Cimetidine Ketoconazole
Digitalis CCBs
Antipsychotics

DRUGS CAUSING HIRSUTISM

Phenytoin
Cyclosporine Pneumonic “PCM”
Minoxidil

DRUGS CAUSING ADDISONIAN LIKE SYNDROME

Busulfan
Ketoconazole
Etomidate

DRUGS CAUSING HEMOLYTIC ANEM IA IN G6PD DEFICIENCY

Sulfonamides Aspirin
Dapsone Nalidixic acid
Primaquine, Quinine Nitrofurantoin
Isoniazid Vitamin K

DRUGS CAUSING AGRANULOCYTOSIS

Phenylbutazone Ticlopidine
Indomethacin Gold compounds
Propylthiouracil Cytotoxics
Methimazole Chloramphenicol
Clozapine Penicillamine

DRUGS CAUSING LEUKOCYTOSIS

Lithium
Corticosteroids

24 HRS HELPLINE: 9891436206/9891334352

 D IAM S 95
2005____________________________________________ PHARMACOLOGY
DRUGS CAUSING MEGALOBLASTIC ANEM IA
Co-trimoxazole Phenytoin
Folate antagonists Phenobarbitone
OCP Trimethoprim

DRUGS CAUSING METHEMOGLOBINAEMIA

Nitrates
Primaquine
Methylene blue
Dapsone

DRUGS CAUSING HYPERURICEMIA

Thiazides Aspirin
Furesemide Pyrazinamide
Ethacrynic acid Ethambutol
Busulphan Cyclosporine

DRUGS CAUSING HYPERGLYCEMIA |

Corticosteroids OCP
Glucagon Phenytoin
Growth hormone Thiazides
Adrenaline Diazoxide
Somatostatin Theophylline
Pentamidine

DRUGS CAUSING HYPOKAL EMIA

Alkali induced alkalosis ' ; Mfheralocorticoids
Amphotericin B P2 adrenergic agonists
Corticosteroids Tetracyclines
Diuretics (Furesemide, Thiazides) Laxatives (abused)
Insulin

DRUGS CAUSING HYPERKALEMIA

ACE inhibitors Pottasium salts
Spironolactone Pentamidine
Amiloride Succinylcholine

DRUGS CAUSING OSTEOPOROSIS

Glucocorticoids
Heparin
Thyroxine

DRUGS CAUSING MYOPATHY

Glucocorticoids Clofibrate
Zidovudine Gemfibrozil
Amphotericin B All statins
Chloroquine Cimetidine
Cyclosporine OCP
24 HRS HELPLINE: 9891436206/9891334352
 DIAM S 96
2005 PHARMACOLOGY

DRUGS CAUSING PANCREATITIS

Diuretics (Thiazide, furesemide, ethacrynic acid)
Antiviral (Didanosine, Zalcitabine, Stamivudine)
Anticancer (Azothiaprine, L-asparginase)
Antibiotics (Tetracyclines)
Steroids
Pentamidine

DRUGS CAUSING PSXJEDOMEMBRANOUS COLITIS

Tetracyclines Methyldopa
Clindamycin Reserpine
Ampicillin OCP
Colchicine

DRUGS CAUSING PULMONARY FIBROSIS 1

Busulfan Cyclophosphamide
Amiodarone
Methysergide Acyclovir
Melphalan Nitrofurantoin
Methotrexate

HUM AN TERATOGENIC DRUGS

Drug Abnormality
Thalidomide Phecomelia f ^ \
Androgens Virilization o f female offsprings
Lithium Foetal goiter, Ebstein’s anomaly
Phenytoin Hydantoin syndrome (Cleft lip / palate, Microcephaly)
Valproate Neural tube defects (spina bifida)
Warfarin Chondrodysplasia punctata
Indomethacin Premature closure o f ductus arteriosus
Stilboestrol Vaginal carcinoma in teenage female offspring
Isotretinoin Craniofacial, CNS & CVS defects (ASD)
Phenobarbitone Craniofacial & Cong, heart defects, Resp depression
ACE inhibitors Fetal damage, IUGR, renal damage
Ethanol Fetal alchohol syndrome (Craniofacial defects, Growth & mental
retardation)

24 HRS HELPLINE: 9891436206/9891334352