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MUHS PHARMACOLOGY - 5 MARK ANSWERS

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UNIT 1: GENERAL PHARMACOLOGY

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Q1. Discuss Pharmacokinetics (5 Marks)

1. Absorption

• Movement of drug from site of administration into systemic circulation.
• Factors affecting absorption: route, lipid solubility, ionization (pH), surface area, blood flow.
• Oral drugs undergo first pass metabolism in liver before reaching systemic circulation.
• Bioavailability (F): Fraction of administered dose reaching systemic circulation unchanged.

2. Distribution

• Once absorbed, drug distributes to tissues via blood.
• Depends on: plasma protein binding, lipid solubility, tissue perfusion, blood-brain barrier.
• Volume of distribution (Vd): Apparent volume needed to contain total body drug at observed plasma concentration.
• Vd = Total amount of drug in body / Plasma drug concentration.

3. Metabolism (Biotransformation)

• Primarily in liver (also kidney, gut, lung).
• Phase I reactions: Oxidation, reduction, hydrolysis - via CYP450 enzymes - add functional group.
• Phase II reactions: Conjugation (glucuronidation, sulfation, acetylation) - make drug water-soluble.
• Result: Prodrug activation OR drug inactivation.

4. Excretion

• Renal excretion: Glomerular filtration + tubular secretion - tubular reabsorption.
• Biliary excretion: Large molecules excreted in bile; enterohepatic circulation prolongs action.
• Others: lungs, saliva, sweat, breast milk.

Key Parameters

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Q2. Discuss Routes of Administration (5 Marks)

A. Enteral Routes

B. Parenteral Routes

C. Other Routes

• Inhalation: Rapid onset, local effect in airways (salbutamol inhaler, general anaesthetics).
• Transdermal: Slow, sustained systemic effect, avoids first-pass (GTN patch, fentanyl patch).
• Topical: Local effect on skin/mucous membranes.
• Intrathecal/epidural: Direct CNS drug delivery.

Advantages of IV route:

1. 100% bioavailability
2. Rapid onset
3. Dose can be titrated
4. Large volumes possible

Disadvantages of IV route:

1. Irreversible - cannot withdraw drug
2. Risk of infection, embolism
3. Requires skilled personnel

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Q3. Discuss Adverse Drug Reactions (ADR) and Reporting (5 Marks)

Classification (Rawlins & Thompson)

• Related to pharmacological action of the drug.
• Dose-dependent, common, reversible on dose reduction.
• Example: Bleeding with warfarin, hypoglycemia with insulin.

• Not related to pharmacological action; idiosyncratic/immunological.
• Dose-independent, rare, potentially severe.
• Example: Anaphylaxis to penicillin, agranulocytosis with clozapine.

• Related to cumulative dose over long-term therapy.
• Example: HPA axis suppression with prolonged corticosteroids.

• Appear after a lag period; teratogenicity (thalidomide), carcinogenicity.

• Withdrawal reactions; Example: Rebound hypertension on stopping clonidine.

Common ADR Examples

• Opioids: Constipation, respiratory depression
• Aminoglycosides: Ototoxicity, nephrotoxicity
• Tetracycline: Discoloration of teeth in children
• NSAIDs: GI ulceration, renal impairment

ADR Reporting (Pharmacovigilance)

• Purpose: Detect, assess, understand, and prevent adverse effects.
• In India: Pharmacovigilance Programme of India (PvPI) - under CDSCO.
• Who reports: Doctors, nurses, pharmacists, patients.
• How: Yellow card (UK), MedWatch (USA), Vigiflow (WHO).
• Causality assessment tools: Naranjo Scale, WHO-UMC criteria.

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Q4. Discuss Factors Modifying Drug Effect (5 Marks)

1. Patient-Related Factors

• Neonates: Immature liver/kidneys, high % body water, reduced plasma proteins → higher drug sensitivity.
• Elderly: Reduced hepatic/renal clearance, polypharmacy, altered body composition.

• Slow acetylators (INH toxicity) vs. fast acetylators.
• G6PD deficiency → hemolysis with primaquine/dapsone.
• CYP2D6 poor metabolizers → toxicity with codeine.

2. Physiological Factors

• Pregnancy: Altered Vd, hepatic metabolism increases, avoid teratogenic drugs.
• Disease states: Liver disease impairs metabolism; renal disease impairs excretion.

3. Pharmacological Factors

• Tachyphylaxis (rapid) - amphetamines
• Chronic tolerance - opioids, nitrates

• Pharmacokinetic (one drug alters ADME of another): Enzyme induction (rifampicin reduces OCP efficacy).
• Pharmacodynamic (additive, synergism, antagonism): Alcohol + sedatives → CNS depression.

4. Environmental Factors

• Smoking: Induces CYP1A2 → reduces plasma levels of theophylline, clozapine.
• Diet: Grapefruit juice inhibits CYP3A4 → increases levels of statins, calcium channel blockers.

5. Route and Dose

• Higher dose → greater effect (up to ceiling).
• IV > IM > SC > oral in speed of onset.

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UNIT 2: CNS DRUGS

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Q5. Alcohols + Sedatives & Hypnotics (5 Marks)

A. ETHYL ALCOHOL (Ethanol)

• Enhances GABA-A receptor activity (CNS depression).
• Inhibits NMDA glutamate receptors.
• Inhibits adenylyl cyclase.

• 30-80 mg%: Euphoria, disinhibition
• 80-200 mg%: Ataxia, slurred speech
• 200-300 mg%: Stupor

• 400 mg%: Coma, respiratory failure, death

B. SEDATIVES AND HYPNOTICS

1. Benzodiazepines: Diazepam, lorazepam, temazepam, nitrazepam
2. Non-benzodiazepine hypnotics (Z-drugs): Zolpidem, zopiclone, zaleplon
3. Barbiturates: Phenobarbitone (now mainly anticonvulsant)
4. Others: Melatonin, ramelteon

• Bind to BZD site on GABA-A receptor → increase frequency of Cl- channel opening → hyperpolarization → CNS depression.

• Insomnia (short-term)
• Anxiety disorders
• Status epilepticus (IV diazepam/lorazepam)
• Alcohol withdrawal
• Preoperative medication

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Q6. Anti-convulsants (5 Marks)

Classification

Phenytoin - Detailed

• Mechanism: Prolongs inactivation of Na+ channels; reduces repetitive neuronal firing.
• Uses: Tonic-clonic and partial seizures; status epilepticus (IV).
• Side effects: Gingival hyperplasia, hirsutism, ataxia, nystagmus, teratogenicity (fetal hydantoin syndrome), zero-order kinetics (narrow TI).

Sodium Valproate - Detailed

• Mechanism: Blocks Na+ channels + inhibits GABA transaminase → increases GABA levels.
• Uses: Broad spectrum - absence, tonic-clonic, myoclonic, Lennox-Gastaut.
• Side effects: Hepatotoxicity, pancreatitis, weight gain, teratogenicity (neural tube defects), tremor, alopecia.
• Contraindicated in pregnancy (use lamotrigine/levetiracetam instead).

Status Epilepticus Management

1. IV lorazepam (first-line)
2. IV phenytoin/fosphenytoin
3. IV phenobarbitone
4. Thiopentone anesthesia (refractory)

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Q7. Drug Therapy in Parkinsonism (5 Marks)

Drug Classification

• Trihexyphenidyl (Benzhexol), Procyclidine.
• Useful for tremor and rigidity.
• Side effects: Dry mouth, constipation, urinary retention, confusion, glaucoma.
• Avoid in elderly due to cognitive effects.

• Peripheral: Nausea, vomiting, hypotension, cardiac arrhythmias (minimized by carbidopa).
• Central: Dyskinesias, on-off phenomena, hallucinations, psychosis.

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Q8. Analgesics and Antipyretics - Gout and Rheumatoid Arthritis (5 Marks)

A. ANALGESICS & ANTIPYRETICS - NSAIDs

1. Non-selective COX inhibitors: Aspirin, ibuprofen, naproxen, diclofenac, indomethacin.
2. Selective COX-2 inhibitors (Coxibs): Celecoxib, etoricoxib.
3. Preferential COX-2: Nimesulide, meloxicam.

• Low dose (75-150 mg): Antiplatelet (irreversible TXA2 inhibition).
• Analgesic/antipyretic dose: 600 mg.
• Anti-inflammatory: 2-4 g/day.
• Side effects: GI ulceration, bleeding, Reye's syndrome (children), tinnitus (salicylism).

B. DRUGS FOR GOUT

• Colchicine: Inhibits tubulin polymerization → impairs neutrophil migration. Side effects: Diarrhea, nausea.
• NSAIDs: Indomethacin, naproxen (drug of choice in acute gout).
• Corticosteroids: For patients who cannot use NSAIDs.

• Allopurinol (xanthine oxidase inhibitor): Reduces uric acid synthesis. Side effects: Rash, Stevens-Johnson syndrome, GI upset.
• Febuxostat: Selective xanthine oxidase inhibitor (alternative to allopurinol).
• Probenecid: Uricosuric agent - blocks uric acid reabsorption in renal tubules.

C. DRUGS FOR RHEUMATOID ARTHRITIS (RA)

• Anti-TNF: Infliximab, etanercept, adalimumab.
• IL-6 inhibitor: Tocilizumab.
• CD20 (B-cell): Rituximab.

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Q9. Psycho-therapeutics (5 Marks)

A. ANTIPSYCHOTICS (Neuroleptics)

• Mechanism: Block D2 dopamine receptors (mesolimbic pathway).
• Uses: Schizophrenia (positive symptoms), mania, antiemetic.
• Side effects: EPS (extrapyramidal symptoms) - dystonia, akathisia, parkinsonism, tardive dyskinesia; sedation; hyperprolactinemia.

• Mechanism: Block D2 + 5-HT2A receptors (lower EPS risk).
• Clozapine: Most effective for refractory schizophrenia. Risk: Agranulocytosis (mandatory WBC monitoring).
• Side effects: Metabolic syndrome, weight gain, sedation.

B. ANTIDEPRESSANTS

C. ANXIOLYTICS

• Benzodiazepines (short-term): Alprazolam, lorazepam.
• Buspirone (5-HT1A partial agonist): Non-sedating, no dependence, delayed onset (2 weeks).
• SSRIs: First-line for GAD long-term.

D. MOOD STABILIZERS

• Lithium: For bipolar disorder; narrow therapeutic index (0.6-1.2 mEq/L); side effects: tremor, polyuria, thyroid dysfunction, nephrogenic DI, teratogenicity (Ebstein's anomaly).
• Alternatives: Valproate, carbamazepine, lamotrigine (bipolar depression).

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Q10. Local Anaesthetics and Counterirritants (5 Marks)

A. LOCAL ANAESTHETICS (LA)

• Block voltage-gated Na+ channels in the inactive state.
• Prevent depolarization → block nerve conduction in sequence: autonomic > sensory (pain, temp, touch) > motor.
• Act better in unionized form (penetrate nerve membrane) but bind receptor in ionized form.
• More effective in alkaline pH; less effective in infected (acidic) tissue.

• Causes vasoconstriction → delays absorption → prolongs action.
• Reduces systemic toxicity.
• Contraindicated for ring block (fingers, toes, penis, nose, pinna) - risk of ischemia.

• Surface/topical anesthesia (EMLA cream, cocaine for nasal surgery).
• Infiltration anesthesia.
• Nerve block (dental, regional).
• Epidural/spinal anesthesia.
• IV regional (Bier's block).

• CNS: Perioral numbness, tinnitus, convulsions, coma.
• CVS: Hypotension, arrhythmias, cardiac arrest.

B. COUNTERIRRITANTS

1. Rubefaction (redness, warmth)
2. Vesication (blister formation)
3. Pustulation
4. Escharotic (tissue destruction)

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UNIT 3: ANS DRUGS

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Q11. Adrenergic Drugs (5 Marks)

Adrenergic Receptor Types

Classification of Adrenergic Drugs

• Actions: ↑HR, ↑BP (systolic), bronchodilation, mydriasis, hyperglycemia, ↑metabolic rate.
• Uses: Anaphylaxis (IM 0.5 mg of 1:1000), cardiac arrest (IV 1 mg of 1:10,000), acute severe asthma, with LA.
• Side effects: Palpitations, hypertension, arrhythmias, cerebral hemorrhage.

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Q12. Cholinergic Drugs (5 Marks)

Cholinergic Receptors

Classification of Cholinergic Drugs

1. Direct-acting Muscarinic:
   • Acetylcholine (ACh): Non-selective, rapid hydrolysis.
   • Pilocarpine: M3 agonist - used for glaucoma (miosis, reduces IOP), dry mouth (Sjogren's).
   • Carbachol, bethanechol: Postoperative urinary retention, paralytic ileus.
2. Anticholinesterases (Indirect-acting):
   • Inhibit AChE → ACh accumulates at all cholinergic synapses.
   • Reversible: Physostigmine (glaucoma, atropine OD antidote), neostigmine (myasthenia gravis, reversal of NDMR), pyridostigmine (myasthenia gravis), edrophonium (Tensilon test).
   • Irreversible (Organophosphates): Malathion, parathion - insecticides; tabun, sarin - nerve agents. Toxicology: SLUD (Salivation, Lacrimation, Urination, Defecation) + muscle paralysis, seizures.
   • Treatment of OP poisoning: Atropine (large doses, IV) + Pralidoxime (PAM, 2-PAM) - regenerates AChE if given early.

• Atropine (prototype):
  • Mechanism: Competitive block of muscarinic receptors.
  • Effects: ↑HR, bronchodilation, decreased secretions, mydriasis + cycloplegia, decreased GI motility, urinary retention.
  • Uses: Premedication, bradycardia, organophosphate poisoning (antidote), irritable bowel syndrome, cycloplegic refraction.
  • Side effects: Dry mouth, tachycardia, blurred vision, urinary retention, constipation, confusion in elderly.
  • Contraindications: Glaucoma, BPH, constipation.
• Other anticholinergics: Scopolamine (motion sickness), Glycopyrrolate, Ipratropium (COPD - inhaled), Oxybutynin (overactive bladder), Benztropine (Parkinsonism).

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Q13. Skeletal Muscle Relaxants (5 Marks)

Classification

1. Non-depolarizing (Competitive) Blockers:
   • Mechanism: Compete with ACh at N (nicotinic) receptors at NMJ; do NOT depolarize.
   • Examples: Tubocurarine (prototype), Pancuronium, Vecuronium, Rocuronium, Atracurium, Cisatracurium.
   • Reversed by: Neostigmine + atropine (or sugammadex for rocuronium/vecuronium).
   • Uses: Surgical muscle relaxation, mechanical ventilation, ECT.
2. Depolarizing Blockers:
   • Mechanism: Activate NMJ (cause initial fasciculations) → persistent depolarization → flaccid paralysis.
   • Succinylcholine (Suxamethonium): Only clinically used drug; shortest acting (5-10 min).
   • Onset: 30-60 seconds - used for rapid sequence intubation (RSI).
   • Cannot be reversed; wait for plasma cholinesterase to metabolize it.
   • Side effects: Hyperkalemia (dangerous in burns, crush injury, denervation), malignant hyperthermia (treat with dantrolene), prolonged apnea in pseudocholinesterase deficiency, postoperative myalgia, raised IOP/ICP.

• Dantrolene: Blocks Ca2+ release from sarcoplasmic reticulum (ryanodine receptor).
• Uses: Malignant hyperthermia (emergency), neuroleptic malignant syndrome, spasticity.

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UNIT 4: CVS DRUGS

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Q14. Anti-hypertensive Drugs (5 Marks)

Classification of Anti-hypertensives

• Thiazides (Hydrochlorothiazide, chlorthalidone): First-line for uncomplicated HTN. Side effects: Hypokalemia, hyperuricemia, hyperglycemia.
• Loop diuretics (Furosemide): For HTN with CKD/CHF.

• ACE Inhibitors (Ramipril, enalapril, lisinopril): Block ACE → reduce Ang II → vasodilation + decreased aldosterone. First-line in diabetic nephropathy, post-MI. Side effects: Dry cough, hyperkalemia, angioedema.
• ARBs (Losartan, valsartan, telmisartan): Block AT1 receptor. Same indications as ACEi; no cough. Side effects: Hyperkalemia, teratogenic.

• Dihydropyridines (Amlodipine, nifedipine): Vascular selective → vasodilation → lower BP. Side effects: Ankle edema, reflex tachycardia.
• Non-dihydropyridines (Verapamil, diltiazem): Also reduce HR. Used in HTN + angina.

• Atenolol, metoprolol: Reduce CO + renin release → lower BP.
• Preferred in HTN + angina, post-MI, heart failure.
• Avoid in asthma, COPD, AV block.

• Prazosin, doxazosin: Useful in HTN + BPH. Risk: First-dose hypotension.

• Methyldopa (α-methylnorepinephrine, α2 agonist): Drug of choice in pregnancy-induced hypertension.
• Clonidine: α2 agonist, reduces sympathetic outflow. Rebound HTN on sudden withdrawal.

• Hydralazine: Arteriolar dilation; used in hypertensive emergencies in pregnancy.
• Sodium nitroprusside: Hypertensive emergencies; releases NO.
• Minoxidil: Severe refractory HTN; side effect: Hypertrichosis (used topically for baldness).

• IV labetalol, IV hydralazine (in pregnancy), IV sodium nitroprusside, IV GTN.

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Q15. Antianginal Drugs, Antiplatelet Drugs, and Myocardial Infarction (5 Marks)

A. ANTIANGINAL DRUGS

• GTN (Glyceryl trinitrate, Nitroglycerin): Sublingual tablet/spray - onset 2 min; duration 30 min.
• Isosorbide dinitrate (ISDN), Isosorbide mononitrate (ISMN): Oral, longer duration.
• Mechanism: Released as NO → activates guanylate cyclase → ↑cGMP → smooth muscle relaxation → venodilation (predominantly) → reduced preload → reduced myocardial O2 demand.
• Side effects: Headache, flushing, postural hypotension.
• Nitrate tolerance: Develops with continuous use; prevented by nitrate-free interval.
• Contraindication: Phosphodiesterase inhibitors (sildenafil) - severe hypotension.

• Reduce HR and contractility → reduce myocardial O2 demand.
• Drug of choice in stable angina + HTN.
• Avoid in Prinzmetal's angina (may worsen coronary spasm).

• Dihydropyridines (amlodipine): Reduce afterload.
• Verapamil/diltiazem: Also reduce HR.
• Drug of choice in Prinzmetal's/vasospastic angina.

B. ANTIPLATELET DRUGS

C. MYOCARDIAL INFARCTION TREATMENT (MONA)

• Morphine: Pain relief, venodilation.
• Oxygen: If SpO2 < 94%.
• Nitrates: Sublingual GTN.
• Aspirin: 300 mg stat + Clopidogrel/Ticagrelor (DAPT).
• Heparin (anticoagulation).
• Reperfusion: Primary PCI (preferred) or thrombolysis (streptokinase, alteplase).
• Long-term: Aspirin + ACEi + β-blocker + statin.

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Q16. Congestive Cardiac Failure (CCF) - Drug Therapy (5 Marks)

Drug Classification

• Ramipril, enalapril, lisinopril.
• Reduce preload + afterload; prevent cardiac remodeling.
• Proven mortality benefit in all grades of HF.

• Carvedilol (α+β blocker), Bisoprolol, Metoprolol (succinate).
• Counteract excessive sympathetic activation; reduce sudden death.
• Start at low dose, gradually increase ("start low, go slow").

• Furosemide (loop diuretic): Reduces pulmonary and peripheral edema; most effective for congestion.
• Spironolactone/Eplerenone (aldosterone antagonist): Reduce mortality in moderate-severe HF; prevent fibrosis; risk: hyperkalemia.
• Thiazides: Mild HF only.

• Mechanism: Inhibits Na+/K+ ATPase pump → ↑intracellular Na+ → ↑intracellular Ca2+ via Na+/Ca2+ exchanger → positive inotropy.
• Also: Slows HR (vagal effect on AV node) - useful in AF + HF.
• Therapeutic range: 0.5-2 ng/mL (narrow therapeutic index!).
• Toxicity: Nausea, vomiting, yellow-green vision, arrhythmias (PVCs, heart block).
• Digoxin toxicity treatment: Stop digoxin, correct hypokalemia, Digibind (antidigoxin antibodies) for severe toxicity.
• Dose reduced in renal failure and elderly.

• Hydralazine + Isosorbide dinitrate: Alternative if ACEi/ARB intolerant; beneficial in African-Americans.

• Neprilysin inhibitor + ARB → increases natriuretic peptides; superior to ACEi in HFrEF.

• Newest class with proven mortality reduction in HFrEF even in non-diabetics.

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Q17. Drugs in Shock (5 Marks)

Types of Shock

1. Hypovolemic (hemorrhagic, dehydration)
2. Cardiogenic (MI, heart failure)
3. Distributive - Septic, Anaphylactic, Neurogenic
4. Obstructive (PE, tension pneumothorax)

Drug Treatment

• Low (1-5 mcg/kg/min): Renal vasodilation (D1).
• Moderate (5-10 mcg/kg/min): Cardiac stimulation (β1).
• High (>10 mcg/kg/min): Vasoconstriction (α1).

• Adrenaline IM 0.5 mg (1:1000) - FIRST and most important.
• IV fluids.
• IV antihistamines (chlorpheniramine).
• IV corticosteroids (hydrocortisone).
• Nebulized salbutamol for bronchospasm.

• IV fluids (30 mL/kg crystalloid bolus).
• Noradrenaline (vasopressor of choice).
• Broad-spectrum antibiotics (within 1 hour of recognition).
• Vasopressin as adjunct.

• Dobutamine (inotrope).
• Reperfusion (PCI for MI-related).
• IABP/mechanical support in refractory cases.

• Hydrocortisone 200 mg/day in refractory septic shock (relative adrenal insufficiency).

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Q18. Coagulants and Anticoagulants (5 Marks)

A. ANTICOAGULANTS

• Mechanism: Binds antithrombin III → accelerates inactivation of thrombin (IIa) + factor Xa (1000x).
• Route: IV (immediate) or SC.
• Monitoring: APTT (target 1.5-2.5x normal).
• Antidote: Protamine sulfate (1 mg neutralizes 100 units heparin).
• Side effects: Bleeding, HIT (Heparin-Induced Thrombocytopenia) - immune-mediated platelet activation.
• Uses: DVT/PE treatment, MI, cardiac surgery (CPB), renal dialysis, pregnancy.

• Enoxaparin, dalteparin, tinzaparin.
• More anti-Xa than anti-IIa activity; more predictable pharmacokinetics.
• SC once/twice daily; no routine monitoring needed.
• Antidote: Protamine (partially reverses).
• Drug of choice in pregnancy (does not cross placenta).

• Monitoring: INR (target 2-3 for most indications; 2.5-3.5 for mechanical heart valves).
• Drug interactions: Many (CYP2C9 substrate).
• Avoid in pregnancy (crosses placenta - teratogenic in first trimester; risk of fetal hemorrhage).

• Streptokinase, alteplase (tPA), tenecteplase.
• Activate plasminogen → plasmin → fibrinolysis.
• Uses: MI, PE, ischemic stroke.
• Contraindications: Recent surgery, active bleeding, stroke history.

B. COAGULANTS (Hemostatic Agents)

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UNIT 5: RESPIRATORY DRUGS

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Q19. Drugs for Cough (5 Marks)

• Productive (wet) cough: Excess secretion - needs expectorants/mucolytics.
• Non-productive (dry) cough: No secretion - needs antitussives.

A. ANTITUSSIVES (Cough Suppressants)

• Codeine (prototype): Acts on cough center in medulla; also has analgesic and constipating effects. Dose: 10-20 mg. Side effects: Constipation, sedation, dependence.
• Pholcodine: Less addictive codeine analog.
• Dextromethorphan: NMDA antagonist; widely used OTC antitussive. No analgesic activity; safer. Abuse potential at high doses.

• Benzonatate: Local anesthetic action on peripheral cough receptors.
• Noscapine: Opioid derivative without analgesic/addictive properties.

B. EXPECTORANTS

• Mechanism: Increase bronchial secretions (reduce viscosity) or stimulate cough reflex.
• Guaifenesin (glyceryl guaiacolate): Most commonly used OTC expectorant; adequate hydration potentiates it.
• Ammonium chloride, potassium iodide: Reflex expectorants (irritate gastric mucosa → stimulate vagal reflex → bronchial secretion).
• Bromhexine: Mucolytic + expectorant; breaks mucopolysaccharide chains; active metabolite is ambroxol.

C. MUCOLYTICS

• Acetylcysteine (NAC): Breaks disulfide bonds of mucoproteins → reduces viscosity. Also antidote for paracetamol overdose (replenishes glutathione).
• Ambroxol: Active metabolite of bromhexine; stimulates surfactant production + mucolytic.
• Carbocisteine: Reduces sulfomucin, increases sialomucin → less viscous mucus.
• Dornase alfa (DNase): Breaks extracellular DNA in thick secretions (cystic fibrosis).

D. NASAL DECONGESTANTS (for cough due to post-nasal drip)

• Xylometazoline, oxymetazoline: α1 agonists; topical nasal sprays; avoid >3-5 days (rebound congestion/rhinitis medicamentosa).
• Pseudoephedrine: Oral decongestant; raises BP in hypertensives.

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Q20. Bronchial Asthma - Drug Treatment (5 Marks)

Classification of Anti-asthma Drugs

• Short-acting (SABA): Salbutamol (albuterol), terbutaline - onset 5 min, duration 4-6 hrs - reliever/rescue inhaler.
• Long-acting (LABA): Salmeterol, formoterol, indacaterol - duration 12-24 hrs - used as controller (always with ICS).
• Mechanism: Stimulate β2 receptors → ↑cAMP → bronchial smooth muscle relaxation.
• Side effects: Tremors, palpitations, hypokalemia, tolerance.

• Theophylline, aminophylline: PDE inhibitors → ↑cAMP + ↑cGMP → bronchodilation + anti-inflammatory.
• Narrow therapeutic index (10-20 mcg/mL).
• Side effects: Nausea, vomiting, headache, arrhythmias, convulsions at toxic levels.
• Drug interactions: Ciprofloxacin, erythromycin (inhibit CYP1A2 → ↑levels); smoking induces CYP1A2 → ↓levels.

• Ipratropium bromide: Short-acting; inhaled; blocks M3 receptors → bronchodilation; used in acute severe asthma + COPD.
• Tiotropium: Long-acting (24 hrs); mainly in COPD; used as add-on in severe asthma.

• Beclomethasone, budesonide, fluticasone, ciclesonide.
• Mechanism: Reduce airway inflammation; suppress cytokines; reduce eosinophils.
• Side effects: Oropharyngeal candidiasis, dysphonia (use spacer + rinse mouth after use); minimal systemic effects at low-medium doses.

• Montelukast, zafirlukast: Block CysLT1 receptors → reduce bronchoconstriction + inflammation.
• Useful as add-on or in aspirin-sensitive asthma, exercise-induced asthma, allergic rhinitis with asthma.

• Cromoglycate (cromolyn sodium), nedocromil.
• Prevent degranulation of mast cells; used for prophylaxis, especially in exercise-induced or allergic asthma.
• Not useful in acute attacks.

• Step 1: SABA as needed.
• Step 2: Low-dose ICS + SABA prn.
• Step 3: Low-dose ICS + LABA.
• Step 4: Medium-high ICS + LABA.
• Step 5: Biologics / add-on therapy.

• Nebulized salbutamol (repeated)
• Ipratropium bromide (nebulized)
• IV/oral corticosteroids (prednisolone 40 mg or IV hydrocortisone)
• IV magnesium sulfate (bronchodilation)
• Oxygen (maintain SpO2 94-98%)

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Q21. Drugs for COPD (5 Marks)

Drug Management

• Tiotropium (once daily, 18 mcg): Blocks M1, M3 receptors → sustained bronchodilation.
• Aclidinium, Glycopyrronium, Umeclidinium: Other LAMA options.
• Reduce exacerbations, improve exercise tolerance.

• Salmeterol, formoterol, indacaterol, olodaterol.
• Used in combination with LAMA (LABA + LAMA = greater benefit than either alone in moderate-severe COPD).

• SABA: Salbutamol.
• SAMA: Ipratropium.

• Theophylline: Add-on therapy; modest benefit in COPD; narrow therapeutic index.

• Not first-line in COPD (unlike asthma).
• Indicated in GOLD Group E (frequent exacerbators) or eosinophil count ≥ 300 cells/μL.
• Used as triple therapy: ICS + LABA + LAMA (e.g., fluticasone/salmeterol/umeclidinium).
• Side effects: Pneumonia (risk increased with ICS in COPD).

• Roflumilast: Reduces exacerbations in severe COPD with chronic bronchitis.
• Side effects: Weight loss, nausea, diarrhea, psychiatric effects.

• Long-term oxygen therapy (LTOT): For PaO2 < 55 mmHg (or < 60 with cor pulmonale).
• 15-18 hrs/day; only intervention that improves mortality in COPD.
• Caution: O2 flow rates to maintain SpO2 88-92% (risk of hypercapnia with high flow O2 in COPD patients).

• N-Acetylcysteine (NAC): Mucolytic; may reduce exacerbation frequency.
• Azithromycin (prophylactic, 3x/week or daily): Reduces exacerbations in patients with frequent exacerbations.
• Vaccines: Influenza (annual), pneumococcal - reduce exacerbations.

COPD Exacerbation Management:

• SABA + SAMA (nebulized).
• Systemic corticosteroids (prednisolone 40 mg x 5 days).
• Antibiotics if: purulent sputum, increased volume, increased dyspnea (amoxicillin/azithromycin/doxycycline).
• Controlled oxygen.
• NIV (non-invasive ventilation) if PaCO2 ↑ with acidosis.

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Reference: Goodman & Gilman's The Pharmacological Basis of Therapeutics; KD Tripathi Essentials of Medical Pharmacology; Rang & Dale's Pharmacology.

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