Pharmacology of antihistamines and 5-HT antagonists MCQs With Answer

Introduction: This MCQ set on the pharmacology of antihistamines and 5‑HT antagonists is designed for M.Pharm students preparing for Advanced Pharmacology‑I examinations. The questions cover receptor pharmacology (H1–H4, 5‑HT subtypes), mechanisms (inverse agonism, ionotropic vs metabotropic signaling), pharmacokinetics (CYP metabolism, P‑glycoprotein transport), important clinical uses (allergy, peptic ulcer, antiemesis, migraine, appetite stimulation), and critical adverse effects and drug interactions (sedation, anticholinergic effects, QT prolongation, CYP inhibition). Each item emphasizes applied knowledge and reasoning so you can recognize clinical implications, choose appropriate therapies, and anticipate safety concerns in advanced practice and research.

Q1. Which histamine receptor subtype primarily mediates allergic bronchoconstriction and increased vascular permeability?

• H1 receptor
• H2 receptor
• H3 receptor
• H4 receptor

Correct Answer: H1 receptor

Q2. Most clinically used H1 antihistamines act pharmacologically as which of the following at the H1 receptor?

• Competitive neutral antagonists
• Inverse agonists that stabilize the inactive receptor conformation
• Full agonists that cause receptor activation
• Allosteric potentiators of histamine binding

Correct Answer: Inverse agonists that stabilize the inactive receptor conformation

Q3. Which first‑generation H1 antihistamine is most likely to produce pronounced sedation and antimuscarinic effects due to high CNS penetration?

• Diphenhydramine
• Cetirizine
• Loratadine
• Fexofenadine

Correct Answer: Diphenhydramine

Q4. Which second‑generation H1 antihistamine is predominantly excreted unchanged in feces and urine and has minimal CNS penetration due to P‑glycoprotein efflux?

• Fexofenadine
• Loratadine
• Cetirizine
• Desloratadine

Correct Answer: Fexofenadine

Q5. The antiemetic action of 5‑HT3 antagonists (e.g., ondansetron) primarily results from blockade of which type of receptor mechanism?

• G protein‑coupled receptor linked to adenylate cyclase
• Ligand‑gated cation channels on vagal afferents and central neurons
• Tyrosine kinase receptor signaling in the chemoreceptor trigger zone
• Intracellular nuclear receptor modulation of gene transcription

Correct Answer: Ligand‑gated cation channels on vagal afferents and central neurons

Q6. Which of the following is a clinically important adverse effect associated with several 5‑HT3 antagonists, especially at higher doses?

• QT interval prolongation and risk of torsades de pointes
• Severe extrapyramidal symptoms
• Marked sedation and coma
• Profound hypoglycemia

Correct Answer: QT interval prolongation and risk of torsades de pointes

Q7. Ondansetron is primarily metabolized by which cytochrome P450 isoenzyme that mediates many drug interactions?

• CYP3A4
• CYP2E1
• CYP2C9
• CYP2A6

Correct Answer: CYP3A4

Q8. Blockade of 5‑HT2A receptors (e.g., by ketanserin) in platelets and vasculature is expected to produce which effect?

• Enhanced platelet aggregation and thrombus formation
• Inhibition of platelet aggregation and reduced vasoconstriction
• Increased gastric acid secretion
• Bradycardia due to vagal stimulation

Correct Answer: Inhibition of platelet aggregation and reduced vasoconstriction

Q9. Cyproheptadine, a 5‑HT2 antagonist with H1 antihistamine properties, has which notable clinical use beyond allergy treatment?

• Appetite stimulation and treatment of anorexia in select patients
• Primary therapy for refractory hypertension
• First‑line agent for chemotherapy‑induced nausea
• Long‑term prevention of peptic ulcers

Correct Answer: Appetite stimulation and treatment of anorexia in select patients

Q10. Which second‑generation antihistamine was withdrawn or restricted historically because of life‑threatening cardiac arrhythmias related to CYP‑mediated drug interactions?

• Terfenadine
• Loratadine
• Cetirizine
• Fexofenadine

Correct Answer: Terfenadine

Q11. The H2 histamine receptor on gastric parietal cells is coupled to which G protein class to stimulate acid secretion?

• Gs (stimulatory, increases cAMP)
• Gi (inhibitory, decreases cAMP)
• Gq (activates phospholipase C and IP3/DAG)
• G12/13 (regulates cytoskeletal changes)

Correct Answer: Gs (stimulatory, increases cAMP)

Q12. A patient develops dry mouth, urinary retention, and blurred vision after antihistamine use. Which antihistamine property best explains these effects?

• Antimuscarinic (anticholinergic) activity of first‑generation H1 antagonists
• Selective H2 blockade in peripheral tissues
• Direct α‑adrenergic agonism
• Inhibition of monoamine oxidase

Correct Answer: Antimuscarinic (anticholinergic) activity of first‑generation H1 antagonists

Q13. 5‑HT3 antagonists are most effective for which phase of chemotherapy‑induced nausea and vomiting?

• Acute phase (within the first 24 hours)
• Delayed phase (24–120 hours after chemotherapy)
• Anticipatory phase (psychogenic)
• Chemotherapy‑provoked diarrhea

Correct Answer: Acute phase (within the first 24 hours)

Q14. Why do many second‑generation H1 antihistamines cause less sedation than first‑generation agents?

• They are P‑glycoprotein substrates that are actively excluded from the CNS and have low BBB penetration
• They are stronger muscarinic agonists that increase arousal
• They are irreversible H1 receptor agonists that promote wakefulness
• They rapidly cross the blood‑brain barrier and are sequestered in brain tissue

Correct Answer: They are P‑glycoprotein substrates that are actively excluded from the CNS and have low BBB penetration

Q15. Which antihistamine is commonly used to prevent motion sickness because of its strong H1 blockade and anticholinergic activity?

• Promethazine
• Fexofenadine
• Desloratadine
• Ranitidine

Correct Answer: Promethazine

Q16. Which serotonin receptor subtype is an ionotropic receptor and the principal target of antiemetic 5‑HT3 antagonists?

• 5‑HT1
• 5‑HT2
• 5‑HT3
• 5‑HT4

Correct Answer: 5‑HT3

Q17. An antipsychotic causes an acute dystonic reaction. Which H1 antihistamine is frequently used intravenously to relieve acute dystonia due to its antimuscarinic properties?

• Diphenhydramine
• Loratadine
• Ranitidine
• Ondansetron

Correct Answer: Diphenhydramine

Q18. Besides QT prolongation, which gastrointestinal adverse effect is commonly reported with 5‑HT3 antagonists like ondansetron?

• Constipation
• Profuse watery diarrhea
• Marked hypermotility and cramping
• Steatorrhea

Correct Answer: Constipation

Q19. Which 5‑HT2 antagonist also exhibits significant α1‑adrenergic blocking activity and has been studied for antihypertensive effects?

• Ketanserin
• Granisetron
• Cyproheptadine
• Ondansetron

Correct Answer: Ketanserin

Q20. Which H2 receptor antagonist is well known for causing CYP450 inhibition, leading to multiple drug‑drug interactions and endocrine effects such as gynecomastia?

• Cimetidine
• Omeprazole
• Sucralfate
• Misoprostol

Correct Answer: Cimetidine

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