BCSE Pharmacology and Toxicology 5 — Questions and Answers
Question 1: A patient taking isoniazid for tuberculosis develops peripheral neuropathy. What is the mechanism of this adverse effect?
- Isoniazid competes with pyridoxine (vitamin B6) for binding to apoenymes (Correct answer)
- Isoniazid induces CYP2E1 producing hepatotoxic metabolites that damage peripheral nerves
- Isoniazid directly inhibits myelin basic protein synthesis in Schwann cells
- Isoniazid chelates magnesium required for axonal conduction
Correct answer: Isoniazid competes with pyridoxine (vitamin B6) for binding to apoenymes
Isoniazid forms hydrazones with pyridoxal phosphate (active B6), depleting the coenzyme needed for GABA synthesis and amino acid metabolism in peripheral neurons, causing neuropathy preventable with B6 supplementation.
Question 2: Which class of drugs causes hyperkalemia by blocking aldosterone's action in the collecting duct?
- Potassium-sparing diuretics (spironolactone) (Correct answer)
- Loop diuretics (furosemide)
- Thiazide diuretics (hydrochlorothiazide)
- Osmotic diuretics (mannitol)
Correct answer: Potassium-sparing diuretics (spironolactone)
Spironolactone competitively antagonizes aldosterone receptors in the collecting duct, preventing sodium reabsorption and potassium secretion, leading to potassium retention and hyperkalemia.
Question 3: Which toxic effect is associated with methanol poisoning but not ethanol poisoning?
- Severe metabolic acidosis with visual disturbances and blindness (Correct answer)
- Central nervous system depression and respiratory failure
- Wernicke encephalopathy due to thiamine depletion
- Hypoglycemia due to NAD+ depletion
Correct answer: Severe metabolic acidosis with visual disturbances and blindness
Methanol is metabolized to formaldehyde and formic acid by alcohol dehydrogenase; formate accumulates in the retina and optic nerve, causing irreversible blindness and severe anion-gap metabolic acidosis.
Question 4: Beta-blockers are contraindicated in patients with reactive airway disease primarily because they:
- Block beta-2 receptors in bronchial smooth muscle, causing bronchoconstriction (Correct answer)
- Inhibit beta-1 receptors in sinoatrial node, worsening hypoxia-induced tachycardia
- Reduce mucociliary clearance by inhibiting beta-2-mediated secretion
- Decrease hypoxic pulmonary vasoconstriction by vasodilating pulmonary vessels
Correct answer: Block beta-2 receptors in bronchial smooth muscle, causing bronchoconstriction
Non-selective beta-blockers block beta-2 adrenergic receptors in bronchial smooth muscle, preventing epinephrine-mediated bronchodilation and triggering potentially life-threatening bronchoconstriction in asthmatic patients.
Question 5: Cyclosporine prevents organ rejection by blocking which step in T-cell activation?
- Inhibiting calcineurin, preventing NFAT-mediated IL-2 transcription (Correct answer)
- Blocking mTOR signaling and halting T-cell proliferation
- Inhibiting inosine monophosphate dehydrogenase and depleting guanosine nucleotides
- Blocking CD80/CD86-CD28 co-stimulation pathway
Correct answer: Inhibiting calcineurin, preventing NFAT-mediated IL-2 transcription
Cyclosporine binds cyclophilin, and this complex inhibits calcineurin phosphatase, preventing dephosphorylation and nuclear translocation of NFAT, thereby blocking IL-2 gene transcription essential for T-cell clonal expansion.
Question 6: A patient presents with pinpoint pupils, coma, and respiratory depression after suspected heroin overdose. What is the correct first-line management?
- Intravenous naloxone (Correct answer)
- Intravenous flumazenil
- Activated charcoal via nasogastric tube
- Intravenous physostigmine
Correct answer: Intravenous naloxone
Naloxone is a competitive mu-opioid receptor antagonist that rapidly reverses opioid-induced CNS and respiratory depression; its short half-life may require repeated dosing for long-acting opioids.
Question 7: Which mechanism accounts for aspirin's irreversible inhibition of platelet aggregation?
- Acetylation of serine residue on COX-1, permanently blocking thromboxane A2 synthesis (Correct answer)
- Competitive inhibition of ADP P2Y12 receptor on platelets
- Phosphodiesterase inhibition raising cAMP and preventing platelet activation
- Blockade of GPIIb/IIIa fibrinogen receptor on activated platelets
Correct answer: Acetylation of serine residue on COX-1, permanently blocking thromboxane A2 synthesis
Aspirin irreversibly acetylates serine-529 of COX-1 in platelets, permanently inhibiting thromboxane A2 production; since platelets lack nuclei, they cannot synthesize new COX-1 for their entire lifespan (~7–10 days).
BCSE Pharmacology and Toxicology 5
A patient taking isoniazid for tuberculosis develops peripheral neuropathy.
What is the mechanism of this adverse effect?