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PHARMACOLOGY — BDS 1st Year

Kathmandu University | Exam Answer Sheet

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Q1. Classify Anticholinergic Drugs. Write Briefly Mechanism of Action, Indication, and Adverse Effects of the Prototype Anticholinergic Drug (Atropine).

Classification of Anticholinergic (Antimuscarinic) Drugs

• Atropine (prototype)
• Scopolamine (hyoscine)
• Hyoscyamine

1. Quaternary amines (do not cross BBB): Ipratropium, Glycopyrrolate, Propantheline, Homatropine
2. Tertiary amines (cross BBB): Dicyclomine, Oxyphencyclimine

• Benztropine, Trihexyphenidyl (Benzhexol)

• Diphenhydramine, Promethazine

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Prototype: ATROPINE

• Dry mouth (xerostomia), reduced sweating, urinary retention
• Flushing of skin (cutaneous vasodilation)
• Blurred vision, photophobia (cycloplegia, mydriasis)
• Central: confusion, hallucinations, delirium (especially high doses)
• Hyperthermia (reduced sweating)
• Tachycardia, palpitations
• Constipation
• Contraindicated in: glaucoma, prostatic hypertrophy, pyloric stenosis

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Q2. Short Notes: (a) Beta-Adrenergic Blocking Agents (b) Organophosphate Poisoning

(a) Beta-Adrenergic Blocking Agents

1. Non-selective (β1 + β2): Propranolol, Timolol, Nadolol
2. Cardioselective (β1): Metoprolol, Atenolol, Bisoprolol
3. With ISA (Intrinsic Sympathomimetic Activity): Pindolol, Acebutolol
4. With alpha-blocking activity: Labetalol, Carvedilol

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(b) Organophosphate Poisoning

• D - Diarrhea/Defecation
• U - Urination
• M - Miosis, Muscle weakness
• B - Bradycardia, Bronchospasm, Bronchorrhea
• E - Emesis
• L - Lacrimation
• S - Salivation, Sweating, Seizures

1. Atropine - Blocks muscarinic effects; given in large doses (2-4 mg IV repeated until drying of secretions)
2. Pralidoxime (PAM/2-PAM) - Reactivates AChE if given early (before "ageing"); acts at both muscarinic and nicotinic sites

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Q3. Uses and Adverse Effects of Atropine [3 Marks]

Uses of Atropine:

1. Pre-anesthetic medication - reduces oral/respiratory secretions, prevents reflex bradycardia
2. Organophosphate/carbamate poisoning - antidote; counteracts DUMBELS symptoms
3. Ophthalmology - mydriasis and cycloplegia for eye examination
4. Bradycardia - sinus bradycardia, AV block
5. Antispasmodic - biliary and renal colic, irritable bowel syndrome
6. Reversal of neuromuscular blockade - given with neostigmine to prevent bradycardia

Adverse Effects of Atropine:

1. Dry mouth, difficulty in swallowing
2. Blurred vision, photophobia
3. Urinary retention (especially in males with BPH)
4. Constipation
5. Tachycardia
6. Hyperthermia (due to inhibition of sweating)
7. CNS: restlessness, excitement, hallucinations, delirium (high doses)
8. Flushing of face and neck

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Q4. List Reversible Cholinesterase Inhibitors. Write Their Uses and Adverse Effects. [3+2=5]

Reversible Cholinesterase Inhibitors:

Uses:

1. Myasthenia gravis - neostigmine, pyridostigmine (most common use)
2. Glaucoma - physostigmine (eye drops)
3. Post-operative ileus / urinary retention - neostigmine
4. Reversal of non-depolarizing neuromuscular block - neostigmine
5. Alzheimer's disease - donepezil, rivastigmine, galantamine
6. Diagnosis of myasthenia gravis - edrophonium (Tensilon test)
7. Atropine overdose antidote - physostigmine (crosses BBB)

Adverse Effects (due to excess ACh):

1. Increased salivation, lacrimation, sweating
2. Nausea, vomiting, diarrhea, abdominal cramps
3. Bradycardia, hypotension
4. Bronchospasm, increased bronchial secretions
5. Miosis
6. Muscle fasciculations, weakness (nicotinic excess)
7. CNS: anxiety, confusion (physostigmine)

Note: Atropine is given alongside neostigmine to counteract muscarinic side effects.

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Q5. Classify Beta-Adrenergic Blockers with One Example. Write Down Uses, Adverse Effects, and Contraindications. [Mopunolol]

Classification of Beta Blockers:

• Propranolol, Nadolol, Timolol, Sotalol

• Metoprolol, Atenolol, Bisoprolol, Acebutolol

• Labetalol, Carvedilol

• Pindolol, Oxprenolol

Uses (Example: Propranolol):

1. Hypertension
2. Ischemic heart disease (angina, post-MI)
3. Cardiac arrhythmias (SVT, atrial fibrillation)
4. Heart failure (carvedilol, bisoprolol)
5. Hyperthyroidism (symptom control - palpitations, tremor)
6. Migraine prophylaxis
7. Glaucoma (timolol eye drops)
8. Anxiety/performance tremor (propranolol)
9. Pheochromocytoma (with alpha blocker)

Adverse Effects:

1. Bradycardia, heart block
2. Bronchospasm (dangerous in asthmatics - β2 blockade)
3. Cold extremities (peripheral vasoconstriction)
4. Fatigue, lethargy
5. Impotence (sexual dysfunction)
6. Masking of hypoglycemia symptoms in diabetics
7. CNS: nightmares, depression (lipophilic ones - propranolol)
8. Rebound hypertension/angina on abrupt withdrawal

Contraindications:

1. Bronchial asthma / COPD
2. Second or third degree AV block
3. Severe bradycardia
4. Cardiogenic shock / acute decompensated heart failure
5. Uncontrolled diabetes mellitus
6. Peripheral vascular disease / Raynaud's phenomenon
7. Pheochromocytoma (used only with prior alpha blockade)

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Q6. Write Down the Therapeutic Classification of Adrenergic Drugs with Examples. List Any Two Common Uses and Adverse Effects of Adrenaline.

Therapeutic Classification of Adrenergic Drugs:

• α1 agonist: Phenylephrine, Methoxamine
• α2 agonist: Clonidine, Methyldopa

• β1 agonist: Dobutamine
• β2 agonist: Salbutamol (albuterol), Terbutaline, Salmeterol
• β1 + β2 agonist: Isoprenaline

• Adrenaline (Epinephrine) - α1, α2, β1, β2
• Noradrenaline (Norepinephrine) - α1, α2, β1

• Dopamine (at low doses: D1, D2; high doses: α, β)

• Amphetamine, Tyramine, Ephedrine (release stored catecholamines)

• Ephedrine (direct + indirect)

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Adrenaline (Epinephrine):

1. Anaphylactic shock - Drug of choice; given IM (0.5 mg of 1:1000 solution); reverses bronchospasm, hypotension, urticaria
2. Cardiac arrest - IV 1 mg (1:10,000); stimulates cardiac contractions via β1

1. Palpitations, tachycardia, arrhythmias
2. Hypertensive crisis (excessive α1 stimulation)
3. Headache, tremor, restlessness, anxiety
4. Pallor (vasoconstriction)
5. Pulmonary edema (in overdose)
6. Hyperglycemia (glycogenolysis via β2)
7. Tissue necrosis at injection site (due to intense vasoconstriction)

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Q7. Write the Mechanism of Action, Uses, and Adverse Effects of Neostigmine [1+1+1]

Mechanism of Action:

• Nicotinic receptors (NMJ) - increases muscle strength
• Muscarinic receptors - produces parasympathomimetic effects (bradycardia, increased secretions, miosis, etc.)

Uses:

1. Myasthenia gravis - symptomatic treatment; increases ACh at NMJ to improve muscle strength
2. Reversal of non-depolarizing neuromuscular blockers (e.g., pancuronium, vecuronium) post-surgery
3. Post-operative urinary retention / paralytic ileus - stimulates smooth muscle
4. Diagnosis of myasthenia gravis (edrophonium preferred, but neostigmine also used)

Adverse Effects:

1. Bradycardia
2. Increased salivation, sweating, lacrimation
3. Nausea, vomiting, diarrhea, abdominal cramps
4. Bronchospasm, increased bronchial secretions
5. Miosis
6. Muscle cramps and fasciculations
7. Urinary urgency

Atropine is always co-administered to block unwanted muscarinic side effects.

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Q8. List Any Two Common Uses and Adverse Effects of Propranolol.

Two Common Uses:

1. Hypertension - reduces cardiac output (β1 blockade) and reduces renin release; effective as monotherapy or in combination
2. Angina pectoris - reduces heart rate and myocardial oxygen demand; prevents exercise-induced angina

Adverse Effects of Propranolol:

1. Bradycardia and heart block
2. Bronchospasm (β2 blockade - dangerous in asthmatics)
3. Cold extremities (reduced peripheral circulation)
4. Fatigue and exercise intolerance
5. Masking of hypoglycemia in diabetics (blunts tachycardia warning sign)
6. CNS effects: depression, nightmares, sleep disturbances (propranolol is highly lipophilic and crosses BBB)
7. Impotence (sexual dysfunction)
8. Rebound effect on abrupt withdrawal: angina, myocardial infarction

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Q9. Role of Adrenaline in Anaphylactic Shock

Pathophysiology of Anaphylactic Shock:

• Severe vasodilation and hypotension
• Bronchospasm (life-threatening)
• Urticaria, angioedema
• Cardiovascular collapse

Why Adrenaline is the Drug of Choice:

Dose and Route:

• Drug: Adrenaline 1:1000 (1 mg/mL)
• Dose: 0.5 mg (adult) IM in the anterolateral thigh
• Repeat every 5-15 min as needed
• IV route reserved for refractory shock with cardiac monitoring

Supporting Measures:

• Oxygen, IV fluids
• H1 antihistamines (chlorpheniramine)
• Corticosteroids (hydrocortisone) - prevent biphasic reaction
• β2 agonists (salbutamol) for persistent bronchospasm

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Q10. Classify Cholinergic Receptor Agonists. Write Down the Mechanism of Action of Pilocarpine and Mention Its Two Uses.

Classification of Cholinergic Receptor Agonists:

• Choline esters: Acetylcholine, Methacholine, Carbachol, Bethanechol
• Alkaloids: Pilocarpine, Muscarine, Arecoline

• Nicotine, Succinylcholine (at NMJ)

• Reversible: Neostigmine, Physostigmine, Edrophonium
• Irreversible: Organophosphates (malathion, tabun), Carbamates

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Pilocarpine - Mechanism of Action:

• Eye: Stimulates M3 receptors of the circular (sphincter) muscle of iris → miosis (pupil constriction); stimulates ciliary muscle → increases outflow of aqueous humor through trabecular meshwork → reduces intraocular pressure (IOP)
• Exocrine glands: Stimulates salivary and sweat glands → profuse sweating and salivation

Two Uses of Pilocarpine:

1. Glaucoma (Open-angle and closed-angle) - reduces IOP by increasing aqueous humor drainage; applied as eye drops (1-4%)
2. Dry mouth (Xerostomia) - stimulates salivary glands; used in Sjogren's syndrome and radiation-induced xerostomia (oral pilocarpine tablets)

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Q11 / Q12. Write Down the Mechanism of Organophosphorous Poisoning and Mention Its Antidotes [2+1=3]

Mechanism of Organophosphorous Poisoning:

• Muscarinic synapses (postganglionic parasympathetic)
• Nicotinic synapses (NMJ, autonomic ganglia)
• CNS synapses

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Antidotes:

• Mechanism: Competitively blocks muscarinic receptors, counteracts the DUMBELS features
• Dose: 2-4 mg IV every 5-10 min until drying of secretions (end-point)
• Does NOT reverse nicotinic (NMJ) effects - pralidoxime is needed for that
• Large doses required; no defined maximum

• Mechanism: Reactivates AChE by nucleophilic attack; displaces the phosphate group from the AChE serine site, freeing the enzyme
• Must be given early (within 24-48 hrs), before "ageing" occurs
• Effective at both muscarinic and nicotinic (NMJ) sites
• Dose: 1-2 g IV slowly over 15-30 min
• NOT effective for carbamate poisoning (carbamates spontaneously dissociate)

• For seizure control (CNS effects)
• Given as adjunct to atropine and PAM

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GENERAL PHARMACOLOGICAL PRINCIPLES

BDS 1st Year Pharmacology — Kathmandu University Board Exam

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Q1. Define Bioavailability. Explain the Different Factors Affecting Drug Absorption. [1+4=5]

Definition of Bioavailability:

• IV administration: Bioavailability = 100% (by definition)
• Formula: F = (AUC oral / AUC IV) × 100%
• It accounts for both absorption and first-pass metabolism.

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Factors Affecting Drug Absorption:

1. Lipid solubility - Highly lipid-soluble drugs (e.g., diazepam) are absorbed faster via passive diffusion
2. Degree of ionization - Unionized form is more lipid-soluble and better absorbed; governed by pH-partition hypothesis
3. Molecular size - Small molecules diffuse more readily
4. Solubility - Drug must dissolve before absorption; formulation affects this

1. Gastric pH - Affects ionization; acidic pH favors absorption of weak acids (aspirin), alkaline pH favors weak bases
2. Gastric emptying time - Faster emptying → drug reaches small intestine quickly → faster absorption
3. GI motility - Increased motility reduces absorption time; decreased motility may increase absorption of some drugs
4. Splanchnic blood flow - Greater blood flow at absorption site increases the concentration gradient
5. Surface area - Small intestine has villi/microvilli = large surface area, hence the primary site of absorption
6. Presence of food - Food may delay (tetracycline) or enhance (griseofulvin) absorption

1. Intravenous - 100% bioavailability; no absorption barrier
2. Sublingual - Bypasses first-pass; rapid absorption (e.g., nitroglycerine)
3. Oral - Subject to first-pass effect; most common route
4. Intramuscular/Subcutaneous - Good absorption; bypasses GI and liver

• Orally absorbed drugs pass through portal circulation to liver before reaching systemic circulation
• Drugs with high hepatic extraction ratio (e.g., morphine, lidocaine, propranolol) are extensively metabolized → low oral bioavailability
• This significantly reduces the effective dose reaching the target

1. Chelation - Tetracycline binds Ca²⁺, Mg²⁺ (milk/antacids) → insoluble complex → reduced absorption
2. Formulation - Tablet vs. liquid; particle size; enteric coating all affect rate of dissolution and absorption

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Q2. Short Notes on:

(a) Therapeutic Drug Monitoring (TDM)

1. Narrow therapeutic index drugs: digoxin, phenytoin, lithium, gentamicin, vancomycin, theophylline
2. Suspected toxicity or therapeutic failure
3. Patient compliance monitoring
4. Drugs with unpredictable pharmacokinetics (e.g., phenytoin - zero-order kinetics)
5. Organ failure (renal/hepatic) altering drug metabolism

• Trough level - drawn just before next dose; reflects minimum plasma level
• Peak level - drawn at expected peak; reflects maximum plasma level
• Steady state - achieved after ~4-5 half-lives

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(b) First-Pass Metabolism (First-Pass Effect)

• Drugs with high first-pass effect require much higher oral doses than parenteral doses (e.g., morphine: oral:IV ratio = 6:1)
• Some drugs are completely inactivated (e.g., lidocaine cannot be given orally)
• Can be bypassed by sublingual (nitroglycerine), rectal, transdermal, or intravenous routes

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(c) Nomenclature of Drugs with Example

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(d) Adverse Drug Reactions (ADR) with Examples

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(e) Antagonist

1. Competitive (surmountable) - binds to same site as agonist; can be overcome by increasing agonist concentration (e.g., atropine vs. ACh; naloxone vs. morphine)
2. Non-competitive (insurmountable) - binds to allosteric site or irreversibly; cannot be overcome (e.g., phenoxybenzamine)
3. Physiological antagonist - two drugs with opposing actions at different receptors (e.g., histamine vs. adrenaline)
4. Chemical antagonist - direct chemical interaction (e.g., protamine neutralizes heparin)

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(f) Superinfection

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(g) Tachyphylaxis

1. Receptor downregulation or desensitization
2. Depletion of mediators (e.g., ephedrine depletes noradrenaline stores)
3. Substrate depletion

• Ephedrine: repeated doses show diminishing bronchodilation
• Nitroglycerine: tolerance develops rapidly (relieved by nitrate-free intervals)
• LSD: rapid tolerance to psychedelic effects

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(h) Biotransformation

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(i) Drug Dependence

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(j) Plasma Half-Life and its Importance

1. Determines dosing interval - drugs with short t½ require more frequent dosing
2. Predicts time to steady state - achieved after 4-5 half-lives
3. Estimates duration of action
4. Guides dose adjustment in renal/hepatic failure
5. Determines time for drug washout

• Short t½: Penicillin G (30 min) - needs 4-6 hourly dosing
• Long t½: Digoxin (36-48 hr), Amiodarone (weeks) - once daily dosing

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(k) NSAID Adverse Drug Reactions (Type A)

1. GI: Peptic ulcer, GI bleeding, nausea (most common)
2. Renal: Acute kidney injury, sodium/water retention
3. Cardiovascular: Hypertension, increased MI risk (selective COX-2 inhibitors - rofecoxib)
4. Hematological: Platelet inhibition (aspirin - irreversible)
5. Hepatotoxicity (rare)
6. Hypersensitivity: Aspirin-induced asthma, urticaria
7. Reye's syndrome: Aspirin in children with viral illness

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Q3. List Different Routes of Drug Administration with an Example of Each. Write Two Advantages and Two Disadvantages of Sublingual Route. [4+2=6]

Routes of Drug Administration:

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Sublingual Route - Two Advantages:

1. Bypasses first-pass effect - drug is absorbed directly into systemic venous circulation via sublingual veins; therefore, a much smaller dose is needed (e.g., nitroglycerin 0.5 mg SL vs large oral dose)
2. Rapid onset of action - very high vascularity under the tongue allows fast absorption; nitroglycerin acts within 1-2 minutes, making it ideal for acute angina attacks

Sublingual Route - Two Disadvantages:

1. Limited to potent, lipophilic drugs - only drugs that are highly lipid-soluble and required in small doses can be given this way; bulky or water-soluble drugs cannot be administered sublingually
2. Inconvenient for repeated dosing - tablet must be held under tongue without swallowing saliva; not suitable for long-term or high-dose treatment; patient discomfort and local irritation possible

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Q4. Define Drug Absorption. Enlist Various Factors Affecting Drug Absorption. [1+4=5]

Definition of Drug Absorption:

1. Physicochemical - lipid solubility, ionization, molecular size
2. Physiological - GI pH, motility, surface area, blood flow
3. Pharmacological - first-pass effect, food-drug interactions
4. Formulation - dosage form, particle size, coating
5. Route of administration

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Q5. Define Biotransformation. Describe Phase I Reactions. [1+4=5]

Definition of Biotransformation:

• Active drug → inactive metabolite (most common; e.g., diazepam → inactive)
• Active drug → active metabolite (e.g., codeine → morphine)
• Inactive prodrug → active drug (e.g., enalapril → enalaprilat)
• Active drug → toxic metabolite (e.g., paracetamol → NAPQI)

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Phase I Reactions (Functionalization Reactions):

• Catalyzed by Cytochrome P450 (CYP450) enzymes in the smooth ER of hepatocytes
• Types:
  • Aromatic hydroxylation (benzene ring → phenol): Phenytoin
  • Aliphatic hydroxylation: Pentobarbital
  • N-dealkylation: Morphine, diazepam
  • O-dealkylation: Codeine → Morphine
  • Deamination: Amphetamine
  • Sulfoxidation: Chlorpromazine

• Less common; involves adding H₂ or removing O₂
• Example: Chloral hydrate → Trichloroethanol; Halothane reduction

• Cleavage of ester or amide bonds by esterases/amidases
• Example: Aspirin → Salicylic acid + Acetic acid; Procaine hydrolysis; Succinylcholine by plasma cholinesterase

• Enzyme induction (rifampicin, phenobarbitone) → faster metabolism → reduced drug effect
• Enzyme inhibition (erythromycin, ketoconazole) → slower metabolism → drug toxicity

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Q6. Advantage and Disadvantage of Oral and Parenteral Route / Intravenous Route. [8 Marks]

Oral Route:

Parenteral (IV) Route:

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Q7. Define Bioavailability and Bioequivalence. Mention the Clinical Significance of Therapeutic Half-Life. [2+1]

Bioavailability:

Bioequivalence:

Clinical Significance of Therapeutic Half-Life:

1. Dosing frequency - t½ < 4 hr (penicillin): 4-6 hourly; t½ > 24 hr (amiodarone): once daily
2. Time to steady state - 4-5 × t½ to reach steady-state plasma level; important for loading dose decisions
3. Duration of drug effect - longer t½ = longer duration
4. Drug accumulation - drugs with long t½ accumulate with repeated dosing → toxicity risk
5. Dose adjustment - in renal failure, t½ prolonged → reduce dose or increase interval

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Q8. Define Pharmacokinetics and Pharmacodynamics. Discuss Any Four Major Factors Affecting Drug Response. [1+1+4=6]

Pharmacokinetics (PK):

Pharmacodynamics (PD):

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Four Major Factors Affecting Drug Response:

• Neonates/Infants: Immature liver enzymes (CYP450 deficient); reduced renal function; higher body water content → altered Vd; increased BBB permeability
  • Example: Chloramphenicol → "Grey baby syndrome" (neonates cannot conjugate the drug)
• Elderly: Reduced hepatic blood flow and enzyme activity; reduced renal function; increased body fat (altered Vd for lipophilic drugs); polypharmacy and drug interactions
  • Example: Benzodiazepines in elderly → excessive sedation, falls

• Obese patients have increased Vd for lipophilic drugs (e.g., diazepam, thiopental)
• Dose of many drugs calculated per kg body weight (e.g., heparin, gentamicin)
• Lean body weight used for drugs that do not distribute into fat (e.g., digoxin)

• Genetic polymorphisms in drug-metabolizing enzymes alter response:
  • CYP2D6 poor metabolizers - codeine → no morphine conversion; β-blockers accumulate
  • Slow acetylators (NAT2 gene) - isoniazid → peripheral neuropathy
  • G6PD deficiency - primaquine, dapsone → hemolytic anemia
• These explain individual differences in drug efficacy and toxicity

• Hepatic disease: Reduced metabolism of high first-pass drugs (morphine, propranolol) → increased plasma levels → toxicity; reduced protein synthesis → reduced protein binding → increased free drug
• Renal disease: Reduced excretion of renally cleared drugs (digoxin, aminoglycosides, lithium) → drug accumulation
• Thyroid disease: Hyperthyroidism increases digoxin clearance; hypothyroidism slows metabolism
• Cardiac failure: Reduced hepatic blood flow → reduced first-pass metabolism; reduced renal perfusion → drug accumulation

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Q9. Explain Various Types of Drug Antagonism with Suitable Examples. [5]

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Types of Drug Antagonism:

• Antagonist competes with agonist for the same receptor binding site
• Reversible; effect overcome by increasing agonist dose
• Shifts dose-response curve to the right (higher EC50) but Emax unchanged
• Example: Atropine vs. acetylcholine (muscarinic receptor); Naloxone vs. morphine (opioid receptor); Propranolol vs. adrenaline (β-receptor)

• Antagonist binds to an allosteric (different) site or binds irreversibly to the receptor
• Cannot be overcome by increasing agonist concentration
• Shifts dose-response curve to the right with reduced Emax
• Example: Phenoxybenzamine (irreversible α-blocker); Aspirin (irreversible COX inhibition)

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• Two drugs produce opposite physiological effects by acting on different receptors or systems
• Net effect is reduction or cancellation
• Example:
  • Histamine (vasodilation, bronchospasm) vs. Adrenaline (vasoconstriction, bronchodilation)
  • Insulin (lowers blood glucose) vs. Glucagon (raises blood glucose)

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• The antagonist directly reacts chemically with the drug/poison, neutralizing it
• Occurs outside the body (in vivo chemical reaction)
• Example:
  • Protamine sulfate neutralizes heparin (antidote)
  • Chelating agents (EDTA, desferrioxamine) bind heavy metals
  • Dimercaprol (BAL) binds arsenic, mercury

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• One drug reduces plasma concentration of another by altering its ADME (absorption, distribution, metabolism, excretion)
• Not a direct receptor interaction
• Examples:
  • Activated charcoal reduces absorption of paracetamol/aspirin
  • Rifampicin induces CYP450 → reduces plasma levels of warfarin, OCP → treatment failure
  • Antacids reduce absorption of tetracycline (chelation)

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• A partial agonist has lower intrinsic activity (efficacy) than a full agonist; in the presence of a full agonist it acts as a functional antagonist
• Example: Buprenorphine (partial μ-opioid agonist) displaces morphine (full agonist) → precipitates withdrawal and reduces morphine effect

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SAQ Answers:

(a) Enterohepatic Circulation

1. Prolongs drug action - drug is not eliminated but recycled (morphine, oestrogens, chloramphenicol)
2. Accounts for long plasma half-life (ethinyl estradiol: OCP)
3. Interruption by antibiotics (which kill intestinal bacteria) reduces drug levels - e.g., rifampicin reduces OCP effectiveness
4. Example: Digoxin, Leflunomide (A77 1726 metabolite), Morphine

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(b) Agonist and Antagonist

• Full agonist - produces maximum response: Morphine, Salbutamol
• Partial agonist - produces submaximal response: Buprenorphine, Pindolol

• Has affinity but zero intrinsic activity
• Examples: Naloxone (opioid), Atropine (muscarinic), Propranolol (β-adrenergic)

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(c) Fluconazole (Short Note)

1. Oropharyngeal and esophageal candidiasis (HIV patients)
2. Vaginal candidiasis
3. Cryptococcal meningitis (in AIDS)
4. Systemic candidiasis (candidemia)
5. Prophylaxis in immunocompromised patients
6. Tinea versicolor, onychomycosis (off-label)

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(d) Propranolol (Short Note)

1. Hypertension
2. Angina pectoris
3. Arrhythmias (SVT, AF)
4. Hyperthyroidism (tremor, palpitations)
5. Migraine prophylaxis
6. Essential tremor and performance anxiety
7. Post-MI (reduces reinfarction)

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(e) Pralidoxime (2-PAM) (Short Note)

1. Organophosphate insecticide poisoning (malathion, parathion)
2. Nerve agent poisoning (sarin, tabun) - military use
3. Always given with atropine (Atropine handles muscarinic effects; PAM reverses both muscarinic and nicotinic/NMJ effects)

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(f) Advantages of Atenolol over Propranolol

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(g) Types of Antagonist

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