Antihistaminic agents are central to allergy pharmacology for B.Pharm students. This concise introduction covers histamine synthesis, storage, receptor subtypes (H1, H2, H3, H4), tissue distribution, signalling pathways, and clinical relevance. Key concepts include histidine decarboxylase, mast cell and basophil storage, enzymatic inactivation by histamine N‑methyltransferase and diamine oxidase, and receptor coupling (H1‑Gq, H2‑Gs, H3/H4‑Gi). Pharmacology of first‑ and second‑generation H1 blockers, blood–brain barrier penetration, adverse effects, and therapeutic uses (allergic rhinitis, urticaria, peptic ulcer via H2 antagonists) are emphasized. This targeted, keyword‑rich summary prepares you for applied questions and exam practice. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. Which enzyme catalyzes the conversion of histidine to histamine?
- Monoamine oxidase
- Histidine decarboxylase
- Histamine N‑methyltransferase
- Diamine oxidase
Correct Answer: Histidine decarboxylase
Q2. In which cells is histamine predominantly stored for rapid release during allergic reactions?
- Neutrophils
- Endothelial cells
- Mast cells and basophils
- Hepatocytes
Correct Answer: Mast cells and basophils
Q3. Which enzymes are principally responsible for histamine inactivation in tissues and plasma?
- Monoamine oxidase and catechol-O-methyltransferase
- Histamine N‑methyltransferase and diamine oxidase
- Alcohol dehydrogenase and aldehyde dehydrogenase
- Acetylcholinesterase and butyrylcholinesterase
Correct Answer: Histamine N‑methyltransferase and diamine oxidase
Q4. Which G protein and signalling pathway is primarily coupled to the H1 histamine receptor?
- Gs → increased cAMP
- Gi → decreased cAMP
- Gq → phospholipase C → IP3/DAG
- Tyrosine kinase activation
Correct Answer: Gq → phospholipase C → IP3/DAG
Q5. Activation of H2 receptors on gastric parietal cells leads to which intracellular effect?
- Activation of phospholipase C and increased IP3
- Inhibition of adenylate cyclase and decreased cAMP
- Stimulation of adenylate cyclase and increased cAMP
- Opening of ligand‑gated chloride channels
Correct Answer: Stimulation of adenylate cyclase and increased cAMP
Q6. What is the primary physiological role of H3 histamine receptors?
- Stimulate gastric acid secretion
- Act as presynaptic autoreceptors to inhibit histamine release
- Mediate vascular endothelial NO release
- Directly cause mast cell degranulation
Correct Answer: Act as presynaptic autoreceptors to inhibit histamine release
Q7. H4 histamine receptors are primarily involved in which function?
- Cardiac chronotropy
- CNS sedation
- Immune cell chemotaxis and modulation
- Renal tubular acid secretion
Correct Answer: Immune cell chemotaxis and modulation
Q8. The triple response to intradermal histamine consists of which three observable phenomena?
- Fever, chills, hypotension
- Red spot, flare, and wheal
- Edema, necrosis, and scarring
- Petechiae, purpura, and ecchymosis
Correct Answer: Red spot, flare, and wheal
Q9. Why do first-generation H1 antihistamines commonly cause sedation?
- They selectively block peripheral H1 receptors only
- They are substrates for P‑glycoprotein and excluded from the brain
- High lipophilicity and low P‑gp efflux allow CNS penetration
- They irreversibly inhibit histidine decarboxylase
Correct Answer: High lipophilicity and low P‑gp efflux allow CNS penetration
Q10. Which property explains the reduced sedation of most second‑generation H1 antihistamines?
- Greater antimuscarinic activity
- Higher lipid solubility and CNS accumulation
- Peripheral selectivity and P‑glycoprotein–mediated efflux
- Irreversible receptor blockade
Correct Answer: Peripheral selectivity and P‑glycoprotein–mediated efflux
Q11. Many H1 antihistamines act as which of the following at the H1 receptor?
- Full agonists
- Partial agonists
- Inverse agonists
- Noncompetitive antagonists that activate receptor tyrosine kinase
Correct Answer: Inverse agonists
Q12. Which antihistamine is a non‑sedating, fourth‑generation example commonly used for allergic rhinitis and urticaria?
- Diphenhydramine
- Promethazine
- Fexofenadine
- Chlorpheniramine
Correct Answer: Fexofenadine
Q13. Which drug is a classic H2 receptor antagonist used to reduce gastric acid secretion?
- Cimetidine
- Loratadine
- Cetirizine
- Rupatadine
Correct Answer: Cimetidine
Q14. Which antihistamine has significant anticholinergic and antiemetic properties and is often used for motion sickness?
- Loratadine
- Promethazine
- Fexofenadine
- Ranitidine
Correct Answer: Promethazine
Q15. Common anticholinergic adverse effects of first‑generation H1 blockers include:
- Bradycardia and hypoglycemia
- Diarrhea and hypersalivation
- Dry mouth, blurred vision, urinary retention
- Hyperreflexia and mydriasis due to cholinesterase inhibition
Correct Answer: Dry mouth, blurred vision, urinary retention
Q16. Which antihistamine was withdrawn or restricted because of life‑threatening cardiac arrhythmias (torsades de pointes) due to QT prolongation?
- Fexofenadine
- Terfenadine
- Cetirizine
- Loratadine
Correct Answer: Terfenadine
Q17. In the management of anaphylactic shock, which agent is the first‑line treatment?
- Intravenous promethazine
- High‑dose oral antihistamine
- Intramuscular epinephrine
- H2 receptor antagonist alone
Correct Answer: Intramuscular epinephrine
Q18. Stimulation of which histamine receptor subtype is primarily responsible for increased gastric acid secretion?
- H1 receptors on smooth muscle
- H2 receptors on parietal cells
- H3 receptors in the CNS
- H4 receptors on leukocytes
Correct Answer: H2 receptors on parietal cells
Q19. Which histamine receptor functions mainly as a presynaptic regulator of neurotransmitter release in the central nervous system?
- H1
- H2
- H3
- H4
Correct Answer: H3
Q20. Histamine‑induced vasodilation in the microcirculation is primarily mediated by which mechanism?
- Direct smooth muscle cGMP activation via H2 receptors
- Endothelial H1 receptor activation with nitric oxide release
- Beta‑adrenergic receptor stimulation
- Blockade of calcium channels on endothelium
Correct Answer: Endothelial H1 receptor activation with nitric oxide release
Q21. Loratadine is best described pharmacokinetically as:
- A prodrug metabolized by CYP enzymes to active desloratadine
- A drug that is rapidly inactivated by esterases in plasma
- Primarily renally excreted unchanged with no metabolism
- An irreversible H1 receptor antagonist
Correct Answer: A prodrug metabolized by CYP enzymes to active desloratadine
Q22. Which antihistamine is historically preferred in pregnancy due to long clinical experience despite sedating effects?
- Fexofenadine
- Chlorpheniramine
- Terfenadine
- Desloratadine
Correct Answer: Chlorpheniramine
Q23. Which laboratory marker is most specific for mast cell activation in suspected anaphylaxis?
- Plasma histamine measured 24 hours later
- Serum tryptase
- Complete blood count eosinophil count
- Plasma renin activity
Correct Answer: Serum tryptase
Q24. H1 receptor antagonists are most effective clinically for which of the following conditions?
- Acute bronchospasm in severe asthma as monotherapy
- Allergic rhinitis and urticaria
- Bacterial sinusitis
- Peptic ulcer disease due to H. pylori
Correct Answer: Allergic rhinitis and urticaria
Q25. Cromolyn sodium treats allergic symptoms by which mechanism?
- H1 receptor inverse agonism
- H2 receptor blockade
- Mast cell stabilization to prevent degranulation
- Potent systemic immunosuppression
Correct Answer: Mast cell stabilization to prevent degranulation
Q26. Which antihistamine is commonly used as an over‑the‑counter sleep aid due to pronounced sedative properties?
- Diphenhydramine
- Fexofenadine
- Cetirizine
- Loratadine
Correct Answer: Diphenhydramine
Q27. Deficiency of which enzyme is associated with histamine intolerance and increased dietary‑derived histamine symptoms?
- Histidine decarboxylase
- Diamine oxidase (DAO)
- Histamine N‑methyltransferase
- Monoamine oxidase A
Correct Answer: Diamine oxidase (DAO)
Q28. Co‑administration of first‑generation antihistamines with alcohol commonly causes which interaction?
- Reduced oral bioavailability of alcohol
- Enhanced CNS depression and sedation
- Prevention of alcohol metabolism by inhibiting alcohol dehydrogenase
- Increased histamine release from mast cells
Correct Answer: Enhanced CNS depression and sedation
Q29. H1 receptor antagonists are particularly effective at relieving which symptom of allergic conditions?
- Chest tightness from severe bronchoconstriction
- Pruritus (itching)
- Peptic ulcer pain
- Acute bacterial infection
Correct Answer: Pruritus (itching)
Q30. Desloratadine is best described as which of the following?
- An H2 antagonist prodrug with short half‑life
- The active metabolite of loratadine with long duration and minimal sedation
- A first‑generation sedating antihistamine
- An irreversible inhibitor of histidine decarboxylase
Correct Answer: The active metabolite of loratadine with long duration and minimal sedation
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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