Introduction: H2 antagonists are a class of antiulcer drugs that block histamine H2 receptors on gastric parietal cells, reducing intracellular cAMP and inhibiting the H+/K+ ATPase-mediated acid secretion. Key topics for B.Pharm students include classification (imidazole vs non-imidazole derivatives), structure–activity relationships (SAR: heterocyclic/aromatic ring, chain length, guanidine or sulfamoyl moiety), mechanism of action, pharmacokinetics, clinical uses (peptic ulcer disease, GERD, Zollinger–Ellison syndrome, stress ulcer prophylaxis), adverse effects and drug interactions (notably cimetidine and CYP inhibition). Important drugs are cimetidine, ranitidine, famotidine and nizatidine, each differing in potency, safety and metabolic profile. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. Which H2 antagonist contains an imidazole ring and is known for anti-androgenic side effects?
- Cimetidine
- Ranitidine
- Famotidine
- Nizatidine
Correct Answer: Cimetidine
Q2. The primary mechanism by which H2 antagonists reduce gastric acid secretion is:
- Inhibition of gastric proton pump directly
- Antagonism of histamine H2 receptors on parietal cells
- Neutralization of gastric acid in the lumen
- Blockade of muscarinic M3 receptors
Correct Answer: Antagonism of histamine H2 receptors on parietal cells
Q3. Which functional group in H2 antagonists increases binding affinity by mimicking histamine’s side chain and often improves potency?
- Imidazole ring
- Guanidine or substituted guanidine (or sulfamoyl) group
- Carboxylic acid group
- Hydroxyl group
Correct Answer: Guanidine or substituted guanidine (or sulfamoyl) group
Q4. Among common H2 antagonists, which is considered the most potent per mg in reducing acid secretion?
- Cimetidine
- Ranitidine
- Famotidine
- Nizatidine
Correct Answer: Famotidine
Q5. Which SAR feature is critical for H2 antagonists to interact with the H2 receptor binding pocket?
- A long rigid steroidal backbone
- An aromatic or heterocyclic ring linked by a flexible chain to an ionizable group
- A peptide-like chain of amino acids
- An aliphatic hydrocarbon chain with no polar groups
Correct Answer: An aromatic or heterocyclic ring linked by a flexible chain to an ionizable group
Q6. Which H2 antagonist was widely withdrawn or restricted due to NDMA contamination concerns?
- Cimetidine
- Ranitidine
- Famotidine
- Nizatidine
Correct Answer: Ranitidine
Q7. The downstream intracellular messenger reduced by H2 receptor blockade in parietal cells is:
- IP3 (inositol trisphosphate)
- cAMP (cyclic adenosine monophosphate)
- cGMP (cyclic guanosine monophosphate)
- Calcium influx only
Correct Answer: cAMP (cyclic adenosine monophosphate)
Q8. Which adverse effect is most characteristically associated with cimetidine due to endocrine interference?
- Nephrotoxicity
- Gynecomastia and impotence
- Severe hypertension
- Hypoglycemia
Correct Answer: Gynecomastia and impotence
Q9. Famotidine’s distinctive SAR includes which important group that contributes to its high potency?
- Hydroxyl group
- Sulfamoyl (sulfonamide-like) group
- Methyl ester
- Phenylalanine side chain
Correct Answer: Sulfamoyl (sulfonamide-like) group
Q10. Which H2 antagonist is most associated with clinically significant cytochrome P450 inhibition and drug interactions?
- Famotidine
- Cimetidine
- Nizatidine
- Ranitidine
Correct Answer: Cimetidine
Q11. H2 antagonists are most effective in suppressing which component of acid secretion?
- Meal-stimulated acid secretion only
- Nocturnal basal acid secretion
- Acid secretion caused by cholinergic stimulation exclusively
- All gastric secretions equally
Correct Answer: Nocturnal basal acid secretion
Q12. Which pharmacokinetic property commonly requires dose adjustment of famotidine in patients with renal impairment?
- Hepatic metabolism to inactive metabolites
- Primary renal excretion of unchanged drug
- Extensive first-pass metabolism
- Excretion via bile only
Correct Answer: Primary renal excretion of unchanged drug
Q13. In the SAR of H2 antagonists, shortening or lengthening the flexible chain between ring and ionizable group typically:
- Has no effect on activity
- Alters receptor binding and can reduce potency
- Always increases potency
- Converts drug to a PPI
Correct Answer: Alters receptor binding and can reduce potency
Q14. Which clinical condition is NOT an approved indication for H2 antagonists?
- Peptic ulcer disease
- GERD (gastroesophageal reflux disease)
- Zollinger–Ellison syndrome as monotherapy when very severe
- Stress-related mucosal bleeding prophylaxis
Correct Answer: Zollinger–Ellison syndrome as monotherapy when very severe
Q15. Which H2 antagonist has the least potential for drug–drug interactions mediated by hepatic CYP enzymes?
- Cimetidine
- Ranitidine
- Famotidine
- All have equal CYP inhibition
Correct Answer: Famotidine
Q16. The original design of H2 antagonists was based on modification of which endogenous molecule?
- Gastrin
- Histamine
- Acetylcholine
- Prostaglandin E2
Correct Answer: Histamine
Q17. Which statement about H2 antagonists and H. pylori therapy is correct?
- H2 antagonists eradicate H. pylori as monotherapy
- H2 antagonists replace antibiotics in eradication regimens
- H2 antagonists can be used adjunctively for symptomatic relief but are not primary eradication agents
- H2 antagonists increase H. pylori virulence
Correct Answer: H2 antagonists can be used adjunctively for symptomatic relief but are not primary eradication agents
Q18. Which adverse effect is a rare but reported hematological reaction to H2 antagonists?
- Aplastic anemia
- Thrombocytopenia
- Leukocytosis
- Polycythemia vera
Correct Answer: Thrombocytopenia
Q19. A patient on warfarin shows increased INR after starting an H2 antagonist. Which H2 antagonist is the most likely cause?
- Famotidine
- Cimetidine
- Nizatidine
- Ranitidine
Correct Answer: Cimetidine
Q20. Structure–activity studies showed that replacing an imidazole ring in cimetidine improved selectivity and reduced endocrine effects. Which drug exemplifies this improvement?
- Omeprazole
- Ranitidine
- Aluminum hydroxide
- Propranolol
Correct Answer: Ranitidine
Q21. Which H2 antagonist contains a furan ring as part of its heterocyclic structure?
- Cimetidine
- Famotidine
- Ranitidine
- Nizatidine
Correct Answer: Ranitidine
Q22. Which of the following effects is expected after H2 receptor blockade on parietal cells?
- Increased intracellular cAMP and increased acid secretion
- Decreased cAMP and decreased acid secretion
- Unchanged cAMP but increased potassium secretion
- Direct inhibition of pepsinogen release only
Correct Answer: Decreased cAMP and decreased acid secretion
Q23. For stress ulcer prophylaxis in ICU patients, H2 antagonists are used primarily to:
- Eradicate H. pylori
- Reduce gastric acidity and prevent mucosal bleeding
- Neutralize already formed ulcers
- Increase gastric motility
Correct Answer: Reduce gastric acidity and prevent mucosal bleeding
Q24. Which H2 antagonist has a chemical group resembling guanidine, contributing to receptor affinity?
- Cimetidine
- Famotidine
- Omeprazole
- Sucralfate
Correct Answer: Famotidine
Q25. Which parameter is most important when choosing between H2 antagonists and proton pump inhibitors (PPIs) for nocturnal acid breakthrough?
- H2 antagonist’s anti-H. pylori activity
- Ability to inhibit basal nocturnal acid secretion (H2 antagonists are effective)
- Speed of ulcer healing compared to antacids only
- H2 antagonists completely block meal-induced acid spikes like PPIs
Correct Answer: Ability to inhibit basal nocturnal acid secretion (H2 antagonists are effective)
Q26. Which pharmacodynamic property distinguishes famotidine from cimetidine clinically?
- Famotidine causes more CYP inhibition than cimetidine
- Famotidine is more potent and has fewer endocrine interactions
- Famotidine is an H1 receptor antagonist
- Famotidine primarily acts as a mucosal protectant
Correct Answer: Famotidine is more potent and has fewer endocrine interactions
Q27. Which drug class should be monitored for interactions when a patient is started on cimetidine?
- Drugs metabolized by hepatic CYP enzymes (e.g., warfarin, phenytoin)
- Inhaled bronchodilators only
- Topical antibiotics only
- Intravenous fluids
Correct Answer: Drugs metabolized by hepatic CYP enzymes (e.g., warfarin, phenytoin)
Q28. In SAR development, replacing the imidazole nucleus reduced which unwanted effect seen with early H2 antagonists?
- Gastrointestinal tolerance
- Anti-androgenic and endocrine side effects
- Anticholinergic toxicity
- Renal excretion issues
Correct Answer: Anti-androgenic and endocrine side effects
Q29. Which H2 antagonist is contraindicated or used cautiously in severe renal impairment without dose adjustment?
- Cimetidine (no adjustment needed)
- Famotidine (requires dose adjustment)
- Ranitidine (never adjusted)
- All H2 antagonists require no renal considerations
Correct Answer: Famotidine (requires dose adjustment)
Q30. Which experimental SAR modification would likely decrease H2 antagonist potency?
- Maintaining optimal chain length between ring and ionizable group
- Replacing the ionizable guanidine-like group with a neutral bulky nonpolar moiety
- Introducing a sulfamoyl group that can H-bond with receptor residues
- Using heteroaromatic rings compatible with receptor pocket
Correct Answer: Replacing the ionizable guanidine-like group with a neutral bulky nonpolar moiety
I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.
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