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Here are complete answers to all questions:

GROUP - A

Q1 (a) — Prodrug, Advantages, Proprietary vs Non-Proprietary Names (0.5+1.5+2)

Definition of Prodrug (0.5 marks): A prodrug is a pharmacologically inactive (or less active) compound that is converted in the body (by metabolic or chemical processes) into an active drug that produces the desired therapeutic effect.
  • Examples: Enalapril (prodrug) → Enalaprilat (active); Levodopa → Dopamine; Prednisone → Prednisolone; Codeine → Morphine.
Advantages of Prodrigs (1.5 marks):
  1. Improves oral bioavailability (e.g., enalapril is better absorbed than enalaprilat)
  2. Overcomes first-pass metabolism (e.g., levodopa crosses blood-brain barrier; dopamine cannot)
  3. Reduces local adverse effects (e.g., sulfasalazine releases 5-aminosalicylic acid in the colon, minimizing systemic toxicity)
  4. Prolongs duration of action (e.g., depot formulations)
  5. Improves patient acceptability - can mask unpleasant taste or smell
  6. Allows site-specific drug delivery (targeted release)
Proprietary vs Non-Proprietary Names (2 marks):
FeatureProprietary NameNon-Proprietary Name
Also calledBrand name / Trade nameGeneric name / INN (International Non-proprietary Name)
Who gives itPharmaceutical companyWHO / pharmacopoeia
ExampleCalpol, PanadolParacetamol
ExampleBrufenIbuprofen
CostHigherLower
PatentProtected by patentNo patent protection
ConsistencyMay vary between brandsStandardized globally
Memory aidOften catchy, easy to rememberReflects pharmacological class

Q1 (b) — Adrenergic Drugs by Receptor Selectivity + Adrenaline in Anaphylaxis (2+2)

Classification by Receptor Selectivity (2 marks):
A. Alpha (α) selective:
  • α1 selective: Phenylephrine, Methoxamine
  • α2 selective: Clonidine, Methyldopa
B. Beta (β) selective:
  • β1 selective: Dobutamine, Metoprolol (blocker)
  • β2 selective: Salbutamol (albuterol), Terbutaline, Salmeterol
C. Alpha + Beta (non-selective):
  • α + β: Adrenaline (Epinephrine), Noradrenaline (Norepinephrine)
  • β1 + β2: Isoprenaline (Isoproterenol)
D. Dopaminergic:
  • Dopamine (low dose - D1 receptors; higher doses activate β1, then α)
Role of Adrenaline in Anaphylactic Shock (2 marks):
Anaphylaxis is a severe, life-threatening systemic hypersensitivity reaction. Adrenaline is the DRUG OF CHOICE.
Actions that reverse anaphylaxis:
  1. α1 stimulation → Vasoconstriction → Reverses hypotension and peripheral vasodilation; reduces mucosal edema (reduces laryngeal edema)
  2. β1 stimulation → Positive inotropic + chronotropic effect → Increases cardiac output → Combats shock
  3. β2 stimulation → Bronchodilation → Reverses bronchospasm; also suppresses mediator release from mast cells
  4. Overall → Inhibits further release of histamine and other mediators from mast cells and basophils
Dose: 0.5 mg (0.5 mL of 1:1000 solution) IM into the anterolateral thigh - repeated every 5-15 minutes if needed.

Q1 (c) — Routes of Drug Administration + Drugs Not Given Orally (2+2)

Common Routes with Examples (2 marks):
Enteral Routes (GI tract):
  • Oral (PO) - Paracetamol tablets
  • Sublingual (SL) - Glyceryl trinitrate (GTN)
  • Buccal - Buprenorphine
  • Rectal - Diazepam suppositories
Parenteral Routes:
  • Intravenous (IV) - Morphine, antibiotics
  • Intramuscular (IM) - Adrenaline, vaccines
  • Subcutaneous (SC) - Insulin, heparin
  • Intradermal - BCG vaccine
Topical/Local Routes:
  • Transdermal - Nicotine patch, fentanyl patch
  • Inhalation - Salbutamol inhaler
  • Intrathecal - Spinal anaesthesia (bupivacaine)
  • Intraocular/nasal/ear drops
Three Drugs Not Given Orally + Reasons (2 marks):
DrugReason
InsulinDegraded by proteolytic enzymes in the GI tract (peptide hormone); given SC/IV
Adrenaline (Epinephrine)Extensively destroyed by first-pass metabolism in the gut wall and liver; very poor oral bioavailability; given IM/IV
HeparinLarge, highly charged molecule - not absorbed across GI mucosa; given SC or IV
(Bonus) StreptomycinNot absorbed from the gut due to its polarity; must be given IM/IV

Q1 (d) — Anticholinesterase Drugs + OPC Poisoning (1.5+1.5+1)

Anticholinesterase Drugs (1.5 marks):
These are drugs that inhibit the enzyme acetylcholinesterase, thereby increasing the levels of acetylcholine at synapses.
A. Reversible (Short-acting):
  • Physostigmine (Eserine) - crosses BBB; used in glaucoma
  • Neostigmine - does not cross BBB; used in myasthenia gravis, post-op urinary retention
  • Pyridostigmine - used in myasthenia gravis
  • Edrophonium - very short acting; used for diagnosis of myasthenia gravis (Tensilon test)
  • Rivastigmine, Donepezil, Galantamine - used in Alzheimer's disease
B. Irreversible (Organophosphates - OPC):
  • Malathion, Parathion, Diazinon - used as pesticides/insecticides
  • Echothiophate - used in glaucoma
  • Sarin, Tabun - nerve agents
Signs and Symptoms of OPC Poisoning (1.5 marks):
Remembered by the mnemonic SLUDGE (muscarinic effects) + central + nicotinic:
Muscarinic (SLUDGE):
  • Salivation, Lacrimation, Urination, Defecation, Gastric cramps, Emesis
  • Also: Miosis (pin-point pupils), bronchospasm, bradycardia, hypotension, sweating
Nicotinic (neuromuscular junction):
  • Muscle fasciculations, weakness, paralysis
  • Hypertension and tachycardia (initial)
Central Nervous System:
  • Anxiety, restlessness, seizures, coma, respiratory failure (the main cause of death)
Drug Management of OPC Poisoning (1 mark):
  1. Atropine (Drug of choice for muscarinic effects)
    • Large doses: 2-4 mg IV, repeated every 5-10 min until secretions dry up (atropinization)
    • End-point: Dry mouth, clear chest, heart rate >80/min
  2. Pralidoxime (2-PAM, Oximes) - Reactivates the inhibited cholinesterase if given EARLY (before "ageing" of enzyme)
    • Dose: 1-2 g IV slowly; reverses nicotinic effects (muscle paralysis)
  3. Supportive: Diazepam for seizures, oxygen, airway support

Q1 (e) — Adverse Drug Reactions (ADRs): Definition + Types (1+3)

Definition (1 mark): An Adverse Drug Reaction (ADR) is defined as "any response to a drug which is noxious and unintended, and which occurs at doses normally used in humans for prophylaxis, diagnosis, or treatment of disease, or for modification of physiological function" (WHO definition).
Types of ADRs with Examples (3 marks):
Type A - Augmented (Predictable):
  • Dose-dependent, related to pharmacological action
  • Most common type (~80% of all ADRs)
  • Example: Hypoglycemia with insulin; bradycardia with beta-blockers; peptic ulcer with NSAIDs
Type B - Bizarre (Unpredictable):
  • Not dose-related, idiosyncratic, immunological
  • Rare but serious
  • Example: Penicillin anaphylaxis; malignant hyperthermia with halothane; aplastic anemia with chloramphenicol
Type C - Chronic/Continuous:
  • Related to long-term use (cumulative effect)
  • Example: Adrenal suppression with prolonged corticosteroid use; dependence with opioids
Type D - Delayed:
  • Appears after long delay
  • Example: Carcinogenesis with alkylating agents; tardive dyskinesia with antipsychotics
Type E - End-of-use (Withdrawal):
  • Occurs on stopping the drug
  • Example: Rebound hypertension on stopping clonidine; seizures on stopping benzodiazepines
Type F - Failure:
  • Unexpected failure of therapy
  • Example: Oral contraceptive failure with rifampicin (enzyme induction)

Q1 (f) — Compare Agonist & Antagonist; Alkaloid & Glycoside (2+2)

i) Agonist vs Antagonist (2 marks):
FeatureAgonistAntagonist
DefinitionDrug that binds to receptor AND produces a responseDrug that binds to receptor but does NOT produce a response
EfficacyHas intrinsic activity (efficacy > 0)Zero intrinsic activity
ActionMimics the endogenous ligandBlocks the action of agonist
Full agonistProduces maximum response-
Partial agonistProduces submaximal response even at max dose-
TypesFull agonist, partial agonist, inverse agonistCompetitive (reversible), non-competitive (irreversible)
ExampleMorphine (opioid agonist), salbutamol (β2 agonist)Naloxone (opioid antagonist), atropine (muscarinic antagonist)
Clinical useTo stimulate a deficient pathwayTo block excessive stimulation
ii) Alkaloid vs Glycoside (2 marks):
FeatureAlkaloidGlycoside
DefinitionNitrogen-containing organic compound of plant origin with basic reactionCompound containing a sugar (glycone) attached to a non-sugar (aglycone) component
Chemical natureBasic (contains N in ring structure)Not necessarily basic; sugar + aglycone
TasteUsually bitterVariable
ExamplesMorphine, Atropine, Quinine, Caffeine, Cocaine, CodeineDigoxin, Digitoxin (cardiac glycosides); Sennoside (laxative); Salicin
Pharmacological actionCNS effects, anticholinergic, analgesic, antimalarialCardiac stimulation (cardiac glycosides), laxative, antitumor
SourceAlkaline plant extractsPlants (foxglove, senna)
Clinical importanceWide range - analgesics, antihypertensives, CNS drugsDigoxin for heart failure and atrial fibrillation

GROUP - B

Q2 (a) — HTN + T2DM: Drug Choice, Antihypertensives List, MOA/AEs/CIs (2+2+2+1+1)

Suitable Drug + Rationale (2 marks):
The most suitable antihypertensive drugs in a patient with hypertension AND type 2 diabetes mellitus are:
1st choice: ACE Inhibitors (e.g., Ramipril, Enalapril) OR ARBs (e.g., Losartan, Valsartan)
Rationale:
  • Provide RENOPROTECTION by reducing intraglomerular pressure (dilate efferent arteriole > afferent)
  • Reduce proteinuria - slow progression of diabetic nephropathy
  • Do not adversely affect glucose metabolism or lipid profile
  • Reduce cardiovascular mortality in diabetic patients
  • ARBs are preferred if ACE inhibitor causes dry cough (bradykinin-mediated)
Drugs to AVOID:
  • Thiazide diuretics (at high doses): Worsen hyperglycemia and dyslipidemia
  • Beta-blockers (non-selective): Mask hypoglycemic symptoms (except tachycardia), impair insulin release, worsen peripheral circulation
Common Antihypertensive Drugs (2 marks):
  1. Diuretics: Hydrochlorothiazide, Frusemide (loop), Spironolactone
  2. Beta-blockers: Atenolol, Metoprolol, Propranolol
  3. ACE Inhibitors: Enalapril, Ramipril, Lisinopril
  4. ARBs (Angiotensin Receptor Blockers): Losartan, Valsartan, Telmisartan
  5. Calcium Channel Blockers (CCBs): Amlodipine, Nifedipine, Diltiazem, Verapamil
  6. Centrally acting: Methyldopa, Clonidine
  7. Alpha-1 blockers: Prazosin, Doxazosin
  8. Direct vasodilators: Hydralazine, Minoxidil
Mechanism of Action of ACE Inhibitors (2 marks):
ACE (Angiotensin-Converting Enzyme) catalyzes the conversion of Angiotensin I → Angiotensin II. ACE Inhibitors block this step, resulting in:
  • Reduced Angiotensin II → Vasodilation (decreased peripheral resistance) → BP reduction
  • Reduced aldosterone secretion → Reduced sodium and water retention
  • Increased bradykinin (not broken down) → Further vasodilation
Adverse Effects of ACE Inhibitors (1 mark):
  • Dry persistent cough (most common - due to bradykinin accumulation)
  • Hyperkalemia
  • First-dose hypotension
  • Renal impairment (in bilateral renal artery stenosis)
  • Angioedema (rare but dangerous)
  • Fetotoxic (teratogenic - contraindicated in pregnancy)
Contraindications of ACE Inhibitors (1 mark):
  • Bilateral renal artery stenosis
  • Pregnancy (causes fetal renal agenesis, oligohydramnios)
  • Hyperkalemia
  • Previous history of angioedema with ACE inhibitors
  • Severe aortic stenosis

Q2 (b) — Neurotransmitter: Definition, Classification, Criteria of Ideal (2+2)

Definition and Classification (2 marks):
A neurotransmitter is a chemical substance released from presynaptic nerve terminals in response to an action potential, which crosses the synaptic cleft and binds to specific receptors on the postsynaptic membrane to either excite or inhibit it.
Classification:
A. By chemical nature:
  • Amines: Acetylcholine, Dopamine, Noradrenaline, Adrenaline, Serotonin (5-HT), Histamine
  • Amino acids: GABA (inhibitory), Glutamate, Glycine (inhibitory), Aspartate (excitatory)
  • Peptides: Substance P, Enkephalins, Endorphins, Somatostatin, VIP
  • Purines: ATP, Adenosine
  • Gases: Nitric oxide (NO), Carbon monoxide (CO)
B. By action:
  • Excitatory: Glutamate, Acetylcholine, Noradrenaline
  • Inhibitory: GABA, Glycine
Criteria of an Ideal Neurotransmitter (2 marks):
For a chemical substance to be accepted as a neurotransmitter, it must fulfill these criteria:
  1. Presence - The substance must be present in the presynaptic terminal
  2. Synthesis - The enzymes for its synthesis must be present in the neuron
  3. Storage - It must be stored in synaptic vesicles in adequate amounts
  4. Release - It must be released from presynaptic terminal on stimulation (nerve impulse), in a calcium-dependent manner
  5. Receptor - Specific receptors for it must be present on the postsynaptic membrane
  6. Postsynaptic action - Interaction with the receptor must produce a physiological response
  7. Mechanism of removal - There must be a mechanism to terminate its action (reuptake, enzymatic degradation, or diffusion)
  8. Drug mimicry - Application of the substance (or its agonists/antagonists) to the synapse must mimic/block the natural response

Q2 (c) — Bronchial Asthma Drugs + Role of Steroids (2+2)

Drugs Used in Bronchial Asthma (2 marks):
A. Bronchodilators:
  • β2 Agonists (SABA): Salbutamol (albuterol), Terbutaline - for quick relief
  • β2 Agonists (LABA): Salmeterol, Formoterol - for long-term control
  • Methylxanthines: Aminophylline, Theophylline (IV in acute; oral for chronic)
  • Anticholinergics: Ipratropium bromide, Tiotropium (especially useful in COPD + asthma)
B. Anti-inflammatory Drugs:
  • Inhaled Corticosteroids (ICS): Beclomethasone, Budesonide, Fluticasone - mainstay of prophylaxis
  • Systemic corticosteroids: Prednisolone (oral), Hydrocortisone (IV in acute severe asthma)
  • Leukotriene antagonists: Montelukast, Zafirlukast
  • Mast cell stabilizers: Sodium cromoglycate, Nedocromil (prophylaxis)
C. Biologics (newer):
  • Omalizumab (anti-IgE), Mepolizumab (anti-IL5) - for severe refractory asthma
Role of Steroids in Bronchial Asthma (2 marks):
Corticosteroids are the most effective anti-inflammatory drugs in asthma. Their mechanisms include:
  1. Reduce airway inflammation - Inhibit synthesis of prostaglandins, leukotrienes, and cytokines (by inducing lipocortin which inhibits phospholipase A2)
  2. Decrease mucosal edema - Reduce vascular permeability
  3. Reduce mucus secretion - Decrease goblet cell hyperplasia
  4. Decrease bronchial hyperreactivity - Reduce airway responsiveness to stimuli
  5. Upregulate β2 receptors - Prevent downregulation caused by prolonged β2 agonist use
  6. Reduce eosinophil infiltration - Decrease the eosinophilic inflammation characteristic of asthma
Routes:
  • Inhaled (preferred): Beclomethasone, Budesonide - minimal systemic side effects; for maintenance
  • Oral: Prednisolone - for moderate-severe attacks and step-up therapy
  • Intravenous: Hydrocortisone (100-200 mg IV) - for acute severe/life-threatening asthma

Q2 (d) — Diuretics Classification by Efficacy + Frusemide Uses & AEs (2+1+1)

Classification of Diuretics by Efficacy (2 marks):
High Efficacy Diuretics (produce 15-25% Na+ excretion):
  • Loop diuretics: Frusemide (Furosemide), Bumetanide, Ethacrynic acid, Torsemide
  • Site: Thick ascending loop of Henle
  • Mechanism: Inhibit Na+/K+/2Cl- (NKCC2) cotransporter
Moderate Efficacy Diuretics (5-10% Na+ excretion):
  • Thiazides: Hydrochlorothiazide (HCTZ), Chlorthalidone, Metolazone
  • Site: Early distal convoluted tubule
  • Mechanism: Inhibit Na+/Cl- cotransporter
Low Efficacy Diuretics (1-3% Na+ excretion):
  • Potassium-sparing diuretics:
    • Aldosterone antagonists: Spironolactone, Eplerenone
    • Non-aldosterone: Amiloride, Triamterene
  • Carbonic anhydrase inhibitors: Acetazolamide (also low efficacy)
  • Osmotic diuretics: Mannitol (special category - not used for BP)
Clinical Uses of Frusemide (1 mark):
  1. Acute pulmonary edema (IV - drug of choice)
  2. Congestive heart failure (chronic)
  3. Hypertension (especially with renal impairment)
  4. Edema of hepatic cirrhosis and nephrotic syndrome
  5. Hypercalcemia (forced diuresis with IV saline)
  6. Hyperkalemia
  7. Acute renal failure (to maintain urine output)
  8. Hypertensive emergency
Adverse Effects of Frusemide (1 mark):
  • Electrolyte disturbances: Hypokalemia, hyponatremia, hypomagnesemia, hypocalcemia
  • Metabolic alkalosis (loss of H+ and Cl-)
  • Ototoxicity: Tinnitus, deafness (especially with IV use or aminoglycosides)
  • Hyperuricemia → Precipitates gout
  • Hyperglycemia (less than thiazides)
  • Dehydration and hypovolemia
  • Hyperlipidemia
  • Allergy (sulfonamide-based structure)

Q2 (e) — Glaucoma Drugs by MOA + Why Atropine is Contraindicated (3+1)

Drugs Used in Glaucoma According to Mechanism of Action (3 marks):
Glaucoma involves raised intraocular pressure (IOP). Treatment reduces IOP either by decreasing aqueous humor production or increasing its outflow.
A. Drugs that Decrease Aqueous Humor Production:
  1. Beta-blockers (Topical): Timolol, Betaxolol, Levobunolol
    • Block β2 receptors in ciliary body → Reduce aqueous secretion
  2. Alpha-2 Agonists: Brimonidine, Apraclonidine
    • Decrease aqueous production AND increase uveoscleral outflow
  3. Carbonic Anhydrase Inhibitors:
    • Topical: Dorzolamide, Brinzolamide
    • Systemic: Acetazolamide
    • Inhibit carbonic anhydrase in ciliary epithelium → Reduce HCO3- → Reduce aqueous production
B. Drugs that Increase Aqueous Humor Outflow:
  1. Prostaglandin Analogues (most effective IOP-lowering): Latanoprost, Bimatoprost, Travoprost
    • Increase uveoscleral outflow
    • Given once daily at night; first-line in open-angle glaucoma
  2. Miotics (Cholinomimetics): Pilocarpine (direct), Physostigmine (indirect)
    • Contract ciliary muscle → Opens trabecular meshwork → Increases drainage
    • Also constrict pupil (miosis)
  3. Sympathomimetics: Epinephrine, Dipivefrine
    • Increase trabecular and uveoscleral outflow
Why Atropine is Contraindicated in Glaucoma (1 mark):
Atropine is a muscarinic (anticholinergic) antagonist that causes:
  • Mydriasis (pupillary dilation) by blocking sphincter pupillae
  • The dilated pupil causes the peripheral iris to bunch up/thicken, narrowing the iridocorneal angle
  • This obstructs the trabecular meshwork at the angle of the anterior chamber
  • This impairs drainage of aqueous humor from the eye
  • The result is a sudden, dangerous rise in intraocular pressure (acute angle-closure crisis)
Therefore, atropine is absolutely contraindicated in narrow-angle (closed-angle) glaucoma. Even in open-angle glaucoma, it should be used with caution. (Reference: Barash Clinical Anesthesia - "Atropine is contraindicated in patients with narrow-angle glaucoma; pupillary dilation thickens the peripheral iris, narrowing the iridocorneal angle, leading to impaired drainage of aqueous humor and increased IOP.")
Sources: Goodman & Gilman's Pharmacological Basis of Therapeutics | Katzung's Basic & Clinical Pharmacology 16e | Barash Clinical Anesthesia 9e | Harrison's Principles of Internal Medicine 22e
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