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BDS 1st Year Pharmacology - Exam Answers (KU)

ANS (Autonomic Nervous System) - 5 Marks Each

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Q1. Classify Anticholinergic Drugs. Write briefly mechanism of action, indications and adverse effects of the prototype anticholinergic drug (Atropine).

Classification of Anticholinergic Drugs

• Atropine, Scopolamine (Hyoscine)

• Homatropine, Ipratropium, Tiotropium

• Dicyclomine, Glycopyrrolate, Pirenzepine

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Atropine - Prototype Anticholinergic

• Atropine is a competitive antagonist of muscarinic (M1, M2, M3) receptors.
• It blocks the action of acetylcholine (ACh) at muscarinic receptors, preventing the parasympathetic effect.
• It does NOT block nicotinic receptors.

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Indications (Uses):

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Adverse Effects:

• Dry as a Bone - Dry mouth, reduced secretions, constipation, urinary retention
• Blind as a Bat - Blurred vision, mydriasis, cycloplegia
• Red as a Beet - Flushing of skin (vasodilation)
• Hot as a Hare - Hyperthermia (reduced sweating)
• Mad as a Hatter - CNS: restlessness, hallucinations, delirium (especially with high doses)

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

(a) Beta-Adrenergic Blocking Agents

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(b) Organophosphate Poisoning

• OPs irreversibly inhibit acetylcholinesterase (AChE)
• AChE normally breaks down ACh
• ACh accumulates at all cholinergic synapses

• Salivation, Lacrimation, Urination, Defecation, GI distress, Emesis

1. Atropine - blocks muscarinic effects (high doses, 2-4 mg IV, repeated)
2. Pralidoxime (2-PAM) - reactivates AChE if given early (before "aging")
3. Supportive: Diazepam for seizures, airway management

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Q3. Uses and Adverse Effects of Atropine

Uses of Atropine:

1. Organophosphate/Anticholinesterase poisoning - Drug of choice, given in large doses
2. Bradycardia - Sinus bradycardia, AV block
3. Pre-anaesthetic medication - Reduces bronchial and oral secretions
4. Ophthalmology - Mydriasis for fundus examination; cycloplegia for refraction testing
5. Antispasmodic - Peptic ulcer, biliary/renal colic, irritable bowel syndrome
6. Reversal - Counteracts bradycardia caused by neostigmine

Adverse Effects of Atropine:

• Dry mouth (xerostomia) - important in dentistry
• Blurred vision, photophobia, mydriasis
• Urinary retention (contraindicated in BPH)
• Constipation, bloating
• Tachycardia, palpitations
• Hyperthermia (anhidrosis)
• CNS: Restlessness, confusion, delirium (atropine toxicity)
• Acute angle-closure glaucoma (dangerous - contraindicated)

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Q4. List Reversible Cholinesterase Inhibitors. Write uses and adverse effects.

Reversible Cholinesterase Inhibitors:

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Uses:

1. Myasthenia Gravis - Neostigmine, Pyridostigmine (treatment of choice)
2. Glaucoma - Physostigmine (eye drops)
3. Alzheimer's disease - Donepezil, Rivastigmine, Galantamine
4. Diagnosis of Myasthenia Gravis - Edrophonium (Tensilon test)
5. Post-operative - Neostigmine reverses non-depolarizing NMJ blockade
6. Atony of bladder/gut - Neostigmine (post-surgical ileus/urinary retention)
7. Antidote - Physostigmine for anticholinergic (atropine) overdose

Adverse Effects (SLUDGE - cholinergic excess):

• Salivation, lacrimation, miosis, bradycardia
• Nausea, vomiting, diarrhea, abdominal cramps
• Bronchospasm, increased bronchial secretions
• Muscle fasciculations (nicotinic effect)
• CNS (physostigmine/donepezil): headache, dizziness

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Q5. Classify Beta-Adrenergic Blockers with one example. Write uses, adverse effects and contraindications.

Classification:

• Propranolol, Timolol, Nadolol, Sotalol

• Atenolol, Metoprolol, Bisoprolol, Acebutolol

• Pindolol, Acebutolol

• Labetalol, Carvedilol

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Uses (of Propranolol - prototype):

1. Hypertension
2. Angina pectoris (reduces O2 demand)
3. Cardiac arrhythmias (AF, SVT)
4. Post-MI - reduces mortality
5. Heart failure (carvedilol, bisoprolol)
6. Hyperthyroidism - controls symptoms
7. Migraine prophylaxis
8. Anxiety (stage fright) - reduces palpitations
9. Glaucoma (timolol eye drops)
10. Pheochromocytoma (with α-blocker)

Adverse Effects:

• Bradycardia, heart block
• Bronchospasm (avoid in asthma - due to β2 blockade)
• Cold extremities (peripheral vasoconstriction)
• Hypoglycemia masking (masks tachycardia of hypoglycemia - dangerous in diabetics)
• Fatigue, lethargy
• Nightmares, depression
• Rebound hypertension on sudden withdrawal
• Sexual dysfunction

Contraindications:

• Asthma / COPD
• Uncontrolled heart failure
• AV block (2nd, 3rd degree)
• Bradycardia
• Hypoglycemia-prone diabetics
• Peripheral vascular disease
• Prinzmetal (vasospastic) angina

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Q6. Therapeutic Classification of Adrenergic Drugs with Examples. List two common uses and adverse effects of Adrenaline (Epinephrine).

Classification of Adrenergic Drugs:

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Two Common Uses of Adrenaline:

1. Anaphylactic shock - Drug of CHOICE; IM 0.5 mg (1:1000); reverses bronchospasm, hypotension, angioedema
2. Cardiac arrest - IV 1 mg (1:10,000); increases coronary and cerebral perfusion pressure during CPR

Adverse Effects of Adrenaline:

• Palpitations, tachycardia, arrhythmias (ventricular fibrillation risk)
• Hypertension (risk of hemorrhagic stroke)
• Tremor, anxiety, restlessness
• Headache
• Pallor, cold extremities
• Hyperglycemia (β2-mediated glycogenolysis)
• Pulmonary edema (with overdose)

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Q7. Mechanism of Action, Uses and Adverse Effects of Neostigmine

Mechanism of Action:

• Neostigmine is a reversible, competitive inhibitor of acetylcholinesterase (AChE)
• It contains a carbamyl group that binds to the esteratic site of AChE
• This prevents breakdown of ACh, leading to accumulation of ACh at synapses
• It acts at both muscarinic and nicotinic receptors
• Does NOT cross the blood-brain barrier (quaternary ammonium compound)
• Duration of action: 2-4 hours

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Uses of Neostigmine:

1. Myasthenia Gravis - increases ACh at NMJ, improves muscle strength
2. Reversal of non-depolarizing NMJ block (after surgery, e.g., after tubocurarine/vecuronium)
3. Post-operative ileus - stimulates GI motility
4. Urinary retention - (atony of detrusor)
5. Glaucoma (physostigmine preferred)

Adverse Effects:

• Muscarinic: Bradycardia, excessive salivation, lacrimation, nausea, vomiting, abdominal cramps, diarrhea, bronchospasm (give atropine to counteract)
• Nicotinic: Muscle fasciculations, cramps, weakness at high doses
• Overdose causes cholinergic crisis (severe weakness mimics myasthenic crisis)

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Q8. Two Common Uses and Adverse Effects of Propranolol

Two Common Uses:

1. Hypertension - reduces cardiac output by blocking β1 receptors in the heart
2. Angina pectoris - reduces heart rate and myocardial O2 demand

Adverse Effects:

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Q9. Role of Adrenaline in Anaphylactic Shock

What is Anaphylactic Shock?

Why Adrenaline is the Drug of Choice:

Dosing:

• Adult: 0.5 mg IM (1:1000 solution) into anterolateral thigh
• Repeat every 5 minutes as needed
• IV only in cardiac arrest (1 mg of 1:10,000)

Additional Treatment:

• Antihistamines (chlorphenamine) - adjunct
• Hydrocortisone - prevents late-phase reaction
• IV fluids, oxygen
• Salbutamol nebulization for bronchospasm

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Q10. Classify Cholinergic Receptor Agonists. Mechanism of Action of Pilocarpine and its Two Uses.

Classification of Cholinergic Agonists:

• Acetylcholine (ACh) - endogenous
• Carbachol, Bethanechol, Methacholine

• Pilocarpine (M1, M3 agonist)
• Muscarine
• Arecolinee

• Reversible: Neostigmine, Physostigmine, Edrophonium, Donepezil
• Irreversible: Organophosphates (malathion, parathion), DFP

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Mechanism of Action of Pilocarpine:

• Pilocarpine is a direct-acting muscarinic agonist (M1 and M3 receptors)
• It mimics ACh at muscarinic receptors
• In the eye:
  • Stimulates M3 receptors on ciliary muscle → contraction → opens trabecular meshwork → increases aqueous humor outflow → reduces intraocular pressure (IOP)
  • Stimulates iris sphincter muscle → miosis (pupil constriction)
• Also stimulates exocrine glands (salivary, lacrimal, sweat glands)

Two Uses of Pilocarpine:

1. Glaucoma (open-angle and angle-closure) - reduces IOP by increasing aqueous drainage; administered as eye drops
2. Xerostomia (dry mouth) - in patients with Sjögren's syndrome or after head/neck radiation therapy; stimulates salivary glands (oral tablet, 5 mg)

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Q11. Mechanism of Organophosphate Poisoning and Its Antidotes

Mechanism of Organophosphate Poisoning:

• Muscarinic sites (parasympathetic effector organs, sweat glands)
• Nicotinic sites (NMJ, autonomic ganglia)
• CNS (brain, spinal cord)

Clinical Features - Remember "DUMBELS":

• Defecation/Diarrhea
• Urination
• Miosis
• Bradycardia, Bronchospasm, Bronchorrhea
• Emesis
• Lacrimation
• Salivation/Sweating

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Antidotes:

• Dose: 2-4 mg IV every 5-10 min until secretions dry
• Blocks muscarinic effects
• Does NOT reverse NMJ paralysis

• Must be given EARLY (before aging occurs, within 24-48 hours)
• Reactivates AChE by displacing OP from the enzyme
• Reverses NMJ paralysis (nicotinic effect)
• Dose: 1-2 g IV slowly

• Controls seizures (CNS effect)

• Airway management, ventilatory support
• Decontamination (remove clothes, wash skin)

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Quick Memory Summary Table

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Sources: Goodman & Gilman's Pharmacological Basis of Therapeutics; Katzung's Basic and Clinical Pharmacology, 16e; Lippincott Illustrated Reviews: Pharmacology.

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General Pharmacological Principles - BDS 1st Year (KU)

5 Marks Each

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Q1. Define Bioavailability. Explain the different factors affecting drug absorption. [1+4=5]

Definition of Bioavailability:

• IV route = 100% bioavailability (reference standard)
• Oral route = less than 100% (due to first-pass metabolism)
• Formula: F = (AUC oral / AUC IV) × 100

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Factors Affecting Drug Absorption:

1. Physicochemical Properties of the Drug

• Lipid solubility: More lipid-soluble drugs cross membranes easily (e.g., diazepam absorbed well)
• Molecular size: Smaller molecules absorbed faster
• Solubility: Drug must dissolve before absorption (dissolution rate)

2. Ionization (pH and pKa - Henderson-Hasselbalch)

• Non-ionized form is lipid soluble → absorbed easily
• Acidic drugs (aspirin, pKa 3.5) - absorbed in acidic stomach (non-ionized)
• Basic drugs (morphine) - absorbed in alkaline intestine
• "Acid in Acid, Base in Base" - absorbed best in same pH environment

3. Route of Administration

• IV > IM > SC > Oral > Rectal > Skin (transdermal slowest)

4. First-Pass Effect (Hepatic)

• Oral drugs pass through liver before systemic circulation
• Extensive first-pass = low bioavailability (e.g., morphine, lidocaine, propranolol)
• Sublingual/rectal/IV avoid first-pass effect

5. GI Factors

• Gastric emptying: Faster emptying → faster absorption from intestine
• Gut motility: Increased motility reduces absorption time
• Gut flora: Can metabolize some drugs before absorption
• Presence of food: Can delay or reduce absorption (e.g., tetracycline with milk)

6. Blood Flow (Perfusion)

• High blood flow to site = faster absorption
• IM > SC (more blood supply)

7. Surface Area

• Small intestine has huge surface area (villi + microvilli) = main absorption site

8. Drug Formulation

• Tablet > capsule > liquid (dissolution rate matters)
• Enteric-coated and sustained-release tablets have modified absorption

9. Drug Interactions

• Antacids chelate tetracycline → reduce absorption
• Proton pump inhibitors change pH → affect drug absorption

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Q2. Short Notes on:

(a) Therapeutic Drug Monitoring (TDM)

• Drugs with narrow therapeutic index (NTI) - small difference between effective and toxic doses
• High inter-patient variability in drug metabolism

• Phenytoin, Aminoglycosides, Immunosuppressants (cyclosporine), Digoxin
• Carbamazepine, Lithium, Oral anticoagulants (warfarin), Theophylline

• Peak concentration (Cmax)
• Trough concentration (Cmin)
• AUC (area under curve)

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

• Morphine (oral bioavailability ~25%)
• Propranolol (~25%)
• Lidocaine (~3%) - cannot be given orally
• Nitroglycerine (~1%) - hence given sublingually
• GTN (glyceryl trinitrate)

• Sublingual (GTN, buprenorphine)
• Transdermal (GTN patches)
• Rectal
• IV/IM/SC
• Inhalation

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(c) Nomenclature of Drugs with Examples

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(d) Adverse Drug Reactions (ADR) with Examples

• Aspirin → gastric ulcer (Type A)
• Chloramphenicol → aplastic anaemia (Type B)
• Penicillin → allergy (Type B)
• Thalidomide → teratogenicity (Type D)

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(e) Agonist and Antagonist

• Full agonist: Produces maximal response (e.g., morphine at opioid receptors)
• Partial agonist: Produces submaximal response even at full receptor occupancy (e.g., buprenorphine)

• Competitive antagonist: e.g., naloxone (reverses morphine)
• Non-competitive antagonist: e.g., phenoxybenzamine (irreversible α-blocker)

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(f) Tachyphylaxis

• Receptor downregulation (decreased receptor number)
• Depletion of mediator (e.g., tyramine depletes noradrenaline stores)
• Desensitization of receptors (uncoupling from G-protein)

• Tyramine → repeated doses cause progressively less BP rise (NE depletion)
• Nitroglycerine → tolerance develops within 24 hours of continuous use
• Ephedrine → tachyphylaxis on repeated use
• Amphetamine

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(g) Superinfection

• Broad-spectrum antibiotics kill normal flora (commensals)
• Resistant organisms or fungi overgrow

• Oral candidiasis (thrush) with tetracycline/ampicillin use
• Pseudomembranous colitis (C. difficile) after clindamycin/ampicillin
• Vaginal candidiasis after ciprofloxacin

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(h) Biotransformation

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(i) Plasma Half-Life (t½) and Its Importance

• Digoxin: t½ = 36-48 hrs (once daily dosing)
• Penicillin: t½ = 30 min (frequent dosing needed)
• Amiodarone: t½ = 40-55 days (very long)

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(j) GPRA (G-Protein Receptor Agonism) / Drug Dependence

• Opioid withdrawal: diarrhea, sweating, muscle cramps, anxiety (opposite of opioid effects)

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

Routes of Drug Administration:

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Sublingual Route - Advantages:

1. Bypasses first-pass metabolism - drug absorbed directly into systemic circulation via sublingual veins → high bioavailability (e.g., GTN would be destroyed in liver if swallowed)
2. Rapid onset of action - highly vascular area under tongue; effects within 1-3 minutes (ideal for acute angina emergency)

Sublingual Route - Disadvantages:

1. Limited drug application - only small, lipid-soluble, potent drugs can be given sublingually; not suitable for large doses or water-soluble drugs
2. Local irritation and inconvenience - tablet must be held under tongue without swallowing; saliva can dissolve it prematurely; some patients find it uncomfortable; cannot eat or drink

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

Definition of Drug Absorption:

Factors Affecting Drug Absorption: (see Q1 above - same content)

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

Definition:

Phase I Reactions - "FUNCTI ON" reactions:

• Enzyme: CYP450 system (mainly CYP3A4)
• Location: Smooth ER of hepatocytes
• Example: Phenobarbitone → hydroxyphenobarbitone; Paracetamol → NAPQI

• Example: Chloramphenicol → arylamine

• Ester hydrolysis: Aspirin → salicylate + acetic acid
• Amide hydrolysis: Lidocaine (plasma esterases)

Phase II Reactions - Conjugation:

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Q6. Advantages and Disadvantages of Oral and Parenteral Routes, and Intravenous Route. [3+3 or similar]

Oral Route:

Parenteral (IM/SC) Route:

Intravenous (IV) Route:

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Q7. Define Bioavailability and Bioequivalence. Clinical Significance of Therapeutic Half-Life. [2+1=3... expanded to 5]

Bioavailability:

Bioequivalence:

• The same active ingredient
• Same dosage form and route
• Similar bioavailability - AUC, Cmax, and Tmax are within 80-125% of each other

Clinical Significance of Therapeutic Half-Life (t½):

1. Determines dosing frequency - Drug with short t½ (penicillin = 30 min) needs q4-6h dosing; long t½ (amiodarone = 40 days) needs once daily or less
2. Time to steady state - Steady state plasma concentration reached in 4-5 half-lives (important for starting drugs like digoxin, warfarin)
3. Duration of drug effect - Guides when drug effect will wear off
4. Time to complete elimination - ~5 half-lives to fully clear a drug (important before switching drugs, e.g., MAOIs)
5. Accumulation and toxicity - Drugs with long t½ can accumulate in renal failure (e.g., digoxin) requiring dose adjustment

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Q8. Define Pharmacokinetics and Pharmacodynamics. Discuss any four major factors affecting drug response.

Pharmacokinetics (PK):

• Study of: ADME = Absorption, Distribution, Metabolism, Excretion
• Parameters: Bioavailability, Vd, t½, clearance, AUC

Pharmacodynamics (PD):

• Study of: Mechanism of action, receptor interactions, dose-response relationships
• Parameters: EC50, Emax, potency, efficacy, therapeutic index

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Four Major Factors Affecting Drug Response:

1. Age

• Neonates/Infants: Immature liver enzymes (CYP450 underdeveloped), immature renal function → drug accumulation → toxicity. E.g., chloramphenicol → Grey Baby Syndrome
• Elderly: Reduced renal function, reduced hepatic blood flow, decreased albumin, increased fat → altered drug PK → use lower doses

2. Body Weight and Composition

• Obese patients: Increased Vd for lipid-soluble drugs (e.g., diazepam)
• Dose often calculated per kg body weight (especially in pediatrics)

3. Genetic Factors (Pharmacogenomics)

• Slow acetylators (INH - isoniazid) → peripheral neuropathy risk
• G6PD deficiency → hemolysis with primaquine, dapsone
• Poor CYP2D6 metabolizers → codeine accumulates

4. Disease States

• Hepatic failure: Reduced first-pass, reduced metabolism → drugs accumulate (e.g., morphine, warfarin)
• Renal failure: Reduced excretion of water-soluble drugs/metabolites (e.g., gentamicin, digoxin)
• Cardiac failure: Reduced liver and kidney perfusion → reduced drug clearance
• Hypoalbuminemia: Reduced protein binding → more free (active) drug → toxicity (e.g., phenytoin, warfarin)

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Q9. Explain Various Types of Drug Antagonism with Suitable Examples. [1+1+4=6 or 5]

Definition of Antagonism:

Types of Drug Antagonism:

1. Pharmacological (Receptor) Antagonism

• Antagonist competes with agonist for the SAME receptor
• Can be overcome by increasing agonist dose
• Shifts dose-response curve to RIGHT (no change in Emax)
• Example: Naloxone blocks morphine at opioid receptors; Atropine blocks ACh at muscarinic receptors; β-blockers block adrenaline

• Antagonist binds irreversibly or at a different allosteric site
• CANNOT be overcome by increasing agonist dose
• Shifts dose-response curve RIGHT with DECREASED Emax
• Example: Phenoxybenzamine (irreversible α-blocker); Aspirin (irreversible COX inhibitor)

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2. Physiological (Functional) Antagonism

• Example: Histamine (bronchoconstriction) vs. Adrenaline (bronchodilation) - opposite effects on bronchi
• Example: Insulin (lowers glucose) vs. Glucagon (raises glucose)

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3. Chemical Antagonism

• Example: Protamine sulfate neutralizes heparin (positive protamine binds negatively charged heparin)
• Example: Chelating agents (desferrioxamine chelates iron; EDTA chelates heavy metals)
• Example: Antacids neutralize gastric acid (not strictly a drug-drug interaction)

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4. Pharmacokinetic Antagonism

• Example: Rifampicin induces CYP450 → increases metabolism of oral contraceptives → OCP failure
• Example: Antacids reduce absorption of tetracycline (chelation)
• Example: Cholestyramine binds warfarin in gut → reduces absorption

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Summary Table:

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SAQ (Short Answer Questions):

(a) Enterohepatic Circulation

• Prolongs drug action (e.g., morphine, estrogens, digitoxin, chloramphenicol)
• If interrupted (by cholestyramine or antibiotics killing gut bacteria) → drug eliminated faster
• Enterohepatic recirculation contributes to the "secondary peaks" in plasma drug concentration curves

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(b) Agonist and Antagonist

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(c) Fluconazole

• Candidiasis (oral, vaginal, esophageal, systemic)
• Cryptococcal meningitis (with flucytosine)
• Prophylaxis in immunocompromised patients

• GI disturbance (nausea, abdominal pain)
• Hepatotoxicity
• Drug interactions (inhibits CYP2C9 - increases warfarin, phenytoin levels)
• QT prolongation

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(d) Propranolol

• Non-selective β-blocker (β1 + β2)
• Uses: Hypertension, angina, arrhythmia, hyperthyroidism, migraine, anxiety
• Adverse: Bronchospasm, bradycardia, hypoglycemia masking
• Contraindicated: Asthma, heart block, PVD

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(e) Pralidoxime (2-PAM)

• Organophosphates (OPs) bind to AChE irreversibly
• Pralidoxime contains an oxime (-NOH) group that has higher affinity for OP than AChE
• It displaces the OP from AChE → reactivates AChE → ACh broken down again
• Must be given EARLY (before "aging" - irreversible conformational change of OP-enzyme complex, which occurs within 24-48 hours)

• Organophosphate poisoning - given with atropine
• Atropine reverses muscarinic effects; Pralidoxime reverses nicotinic (NMJ) effects + muscarinic

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(f) Advantages of Atenolol over Propranolol

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(g) Types of Antagonist

1. Competitive (reversible) - Naloxone, β-blockers, atropine
2. Non-competitive (irreversible) - Phenoxybenzamine, aspirin
3. Physiological/Functional - Adrenaline vs histamine
4. Chemical - Protamine vs heparin, chelators
5. Pharmacokinetic - Rifampicin (inducer), antacids (absorption reducers)

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Master Memory Summary

Sources: Katzung's Basic and Clinical Pharmacology 16e; Goodman & Gilman's Pharmacological Basis of Therapeutics; Lippincott Illustrated Reviews: Pharmacology.