NRE Step 1 Pharmacology MCQs

Answer: Accumulation of bradykinin. ACE also breaks down bradykinin. Inhibiting ACE lets bradykinin (and substance P) build up in the airway, causing a dry cough in up to 1 in 10 patients — the same mechanism underlies angioedema. Switch to an angiotensin receptor blocker such as losartan, which does not affect bradykinin.

• Accumulation of angiotensin II: ACE inhibitors reduce angiotensin II formation, not increase it.
• Beta-receptor blockade in the airways: Lisinopril is an ACE inhibitor, not a beta-blocker, so it does not block airway beta-receptors.
• Hypokalaemia: ACE inhibitors tend to raise potassium, and hypokalaemia does not cause cough.

Answer: Labetalol. Labetalol (an alpha- and beta-blocker) is first-line for hypertension in pregnancy, with nifedipine and methyldopa as alternatives. ACE inhibitors and ARBs are contraindicated because they cause fetal renal damage, oligohydramnios and skull defects. Atenolol is associated with fetal growth restriction.

• Ramipril: Fetotoxic — contraindicated in pregnancy.
• Losartan: Fetotoxic — contraindicated in pregnancy.
• Atenolol: Atenolol is linked to fetal growth restriction, so labetalol, nifedipine or methyldopa are preferred in pregnancy.

Answer: Low-dose ICS–formoterol. Uncontrolled asthma (reliever ≥ 3 times a week or night waking) needs inhaled corticosteroid. GINA (2024) prefers low-dose ICS–formoterol as an anti-inflammatory reliever, stepping up to maintenance and reliever therapy (MART). LABA alone increases asthma deaths. Oral steroids are for exacerbations or severe disease.

• More frequent salbutamol: Over-reliance on SABA is linked to deaths.
• LABA alone: LABA without an inhaled steroid increases asthma deaths and must never be used alone.
• Montelukast alone: An add-on, not the preferred step.

Answer: Full blood count. Clozapine is the only antipsychotic proven for treatment-resistant schizophrenia (after two failed antipsychotics). It can cause agranulocytosis, so FBC is monitored weekly for 18 weeks, then fortnightly, then monthly. Other side effects: myocarditis (early), constipation (can be fatal ileus), hypersalivation, weight gain, diabetes, seizures. Smoking changes its levels (stopping smoking raises levels).

• Serum lithium levels: Lithium levels are monitored for lithium, not clozapine.
• Thyroid function tests: Thyroid function is not the main risk with clozapine; agranulocytosis is.
• ECG for QT interval: Myocarditis matters too, but FBC monitoring is mandatory.

Answer: Fibrates, macrolides, hypothyroidism. Statin-associated muscle symptoms range from myalgia (normal CK) to myositis and rhabdomyolysis (rare). Risk factors: high dose, drug interactions (CYP3A4 inhibitors with simvastatin/atorvastatin — macrolides, azoles, HIV protease inhibitors, amiodarone, diltiazem/verapamil, grapefruit; gemfibrozil; ciclosporin), hypothyroidism (check TSH), renal/hepatic impairment, older age, low body mass, alcohol, vitamin D deficiency. Management: if CK < 5× ULN and tolerable → consider continuing or reducing dose/switching; CK > 10× ULN or severe → stop. Pravastatin/rosuvastatin have fewer CYP3A4 interactions. Ezetimibe (cholesterol absorption inhibitor) and PCSK9 inhibitors are alternatives/add-ons. Statins: check LFTs at baseline, 3 and 12 months.

• Night-time dosing, hypertension: Timing of the dose does not affect myopathy risk.
• Pravastatin, regular exercise: Pravastatin is a lower-risk statin.
• ACE inhibitors, hypertension: ACE inhibitors and hypertension are not risk factors for statin myopathy.

Answer: Albendazole — β-tubulin. Benzimidazoles (albendazole, mebendazole) bind parasite β-tubulin → inhibit microtubule polymerisation and glucose uptake → worm death; used for Ascaris, hookworm, Trichuris, Enterobius (pinworm — treat household), hydatid disease (albendazole, prolonged), neurocysticercosis (with steroids). Avoid in first trimester. WHO school-based deworming: single-dose albendazole 400 mg periodically in endemic areas (children ≥ 1 year, 200 mg 12–23 months). Praziquantel: tapeworms (Taenia) and schistosomiasis. Ivermectin: Strongyloides, onchocerciasis, scabies.

• Ivermectin — β-tubulin: Ivermectin acts on chloride channels.
• Praziquantel — calcium influx: Praziquantel treats tapeworms and schistosomes.
• Pyrantel — depolarising block: Effective, but not used for mass deworming.

Answer: Guanethidine. Adrenergic neurone blockers (guanethidine, bretylium): taken up by NET (uptake-1) into sympathetic nerve terminals, block noradrenaline release → postural/exercise hypotension, diarrhoea, failure of ejaculation; tricyclics block uptake-1 and antagonise their effect. Reserpine depletes vesicular stores (VMAT inhibition — depression). Clonidine: central α2 agonist (rebound hypertension on stopping). Methyldopa: false transmitter/central α2 (pregnancy). Now largely historical except guanethidine for regional sympathetic block.

• Clonidine: Clonidine is a central α2 agonist.
• Prazosin: Prazosin is an α1 blocker.
• Reserpine: Reserpine depletes vesicular stores (VMAT).

Answer: Inhibits bacterial β-lactamase. β-lactamase inhibitors (clavulanic acid, sulbactam, tazobactam, avibactam) bind and inactivate β-lactamases, protecting the partner β-lactam (amoxicillin, ampicillin, piperacillin, ceftazidime) and extending cover to β-lactamase-producing organisms (H. influenzae, Moraxella, S. aureus (MSSA), anaerobes, some Enterobacterales). Co-amoxiclav: cholestatic jaundice (especially older men, longer courses), diarrhoea. MRSA resistance is via altered PBP2a (mecA) — inhibitors don’t help.

• Blocks penicillin-binding proteins: Blocking PBPs is amoxicillin’s action.
• Increases renal excretion: Clavulanate does not increase renal excretion.
• Inhibits bacterial protein synthesis: It does not inhibit protein synthesis.

Answer: Stabilises mast cells. Cromones (sodium cromoglicate, nedocromil): stabilise mast cell membranes, preventing release of histamine and other mediators — prophylactic only (no effect in acute attacks), very safe; used in allergic conjunctivitis (eye drops), allergic rhinitis, exercise-induced asthma (largely superseded by ICS). Other allergy drugs: antihistamines (H1), leukotriene receptor antagonists (montelukast — neuropsychiatric effects), corticosteroids, omalizumab (anti-IgE).

• Blocks H1 histamine receptors: H1 blockade is how antihistamines act.
• Blocks leukotriene receptors: Leukotriene blockade is how montelukast acts.
• Stimulates β2 adrenoceptors: β2 stimulation is how salbutamol acts.

Answer: Slow acetylator phenotype. N-acetyltransferase 2 (NAT2) polymorphism: slow acetylators (≈ 50% of South Asians and Europeans) accumulate drugs → drug-induced lupus (hydralazine, procainamide, isoniazid — anti-histone antibodies, spares kidneys and CNS), isoniazid peripheral neuropathy (give pyridoxine), sulfonamide toxicity; rapid acetylators — lower INH levels and possible treatment failure with intermittent regimens. Other pharmacogenetics: G6PD deficiency (haemolysis), TPMT (azathioprine), HLA-B*15:02 (carbamazepine SJS), pseudocholinesterase deficiency (suxamethonium apnoea), CYP2C19 poor metabolisers (clopidogrel failure).

• Rapid acetylator phenotype: Rapid acetylators have a lower risk.
• CYP2D6 ultra-rapid metaboliser: CYP2D6 ultra-rapid metabolism affects codeine.
• TPMT deficiency: TPMT deficiency affects azathioprine.

Answer: It may precipitate seizures. Flumazenil: competitive GABA-A benzodiazepine-site antagonist; reverses benzodiazepine sedation (e.g. after procedural sedation). In mixed overdoses (especially TCAs — wide QRS — or other proconvulsants) or in benzodiazepine-dependent patients, removing benzodiazepine protection can precipitate seizures and arrhythmias; short half-life → resedation. Benzodiazepine overdose alone is rarely fatal — supportive care (airway, ventilation) is preferred. Naloxone for opioids is safer and widely used.

• It causes respiratory depression: Flumazenil does not cause respiratory depression.
• It is ineffective for benzodiazepines: Flumazenil does reverse benzodiazepines.
• It worsens hypoglycaemia: Flumazenil does not worsen hypoglycaemia.

Answer: Retinopathy. Hydroxychloroquine: antimalarial and DMARD (SLE — reduces flares and mortality; RA, Sjögren); toxicity — irreversible retinopathy (bull’s-eye maculopathy) related to dose (> 5 mg/kg real body weight/day) and duration (risk after ~5 years) — baseline exam and annual screening after 5 years (OCT, visual fields); also skin pigmentation, GI upset, cardiomyopathy (rare), QT prolongation, hypoglycaemia. Safe in pregnancy and lactation.

• Pulmonary fibrosis: Pulmonary fibrosis is caused by methotrexate or amiodarone.
• Peripheral neuropathy: Neuropathy is uncommon.
• Haemorrhagic cystitis: Haemorrhagic cystitis is caused by cyclophosphamide.