Diphenhydramine hydrochloride MCQs With Answer

Diphenhydramine hydrochloride MCQs With Answer is an essential review for B.Pharm students studying antihistamines and clinical pharmacology. This focused set explores diphenhydramine’s chemical form, mechanism as a first‑generation H1 antagonist (inverse agonist), pharmacokinetics, hepatic metabolism, CNS penetration and anticholinergic adverse effects. Questions cover therapeutic uses (allergic disorders, motion sickness, insomnia, extrapyramidal reactions), dosing, formulations, drug interactions (CNS depressants, MAO inhibitors), toxicity management and special‑population cautions. The material emphasizes mechanistic understanding, clinical application and safe use—key competencies for pharmacy practice. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. Which receptor is primarily targeted by diphenhydramine?

• H1 histamine receptor
• H2 histamine receptor
• Muscarinic M2 receptor
• Beta‑2 adrenergic receptor

Correct Answer: H1 histamine receptor

Q2. Diphenhydramine is classified as which generation of antihistamine?

• First‑generation H1 antagonist
• Second‑generation peripheral H1 antagonist
• H2 receptor antagonist
• Selective H3 antagonist

Correct Answer: First‑generation H1 antagonist

Q3. What is the principal pharmacodynamic action of diphenhydramine at the H1 receptor?

• Inverse agonist at H1 receptors
• Full agonist at H1 receptors
• Irreversible antagonist at H1 receptors
• Allosteric activator of H1 receptors

Correct Answer: Inverse agonist at H1 receptors

Q4. Which of the following is a common clinical use of diphenhydramine?

• Allergic rhinitis, urticaria and motion sickness
• Chronic heart failure management
• Long‑term maintenance therapy for asthma
• First‑line therapy for bacterial sinusitis

Correct Answer: Allergic rhinitis, urticaria and motion sickness

Q5. Which adverse effect is most characteristic of diphenhydramine?

• Sedation and anticholinergic effects (dry mouth, urinary retention)
• Severe hypoglycemia
• Hyperkalemia
• Ototoxicity

Correct Answer: Sedation and anticholinergic effects (dry mouth, urinary retention)

Q6. Diphenhydramine’s ability to cause marked sedation is primarily due to:

• Readily crossing the blood–brain barrier and acting centrally
• Selective peripheral H1 blockade only
• Strong alpha‑adrenergic agonism
• Direct GABA receptor agonism

Correct Answer: Readily crossing the blood–brain barrier and acting centrally

Q7. The major route of diphenhydramine metabolism is:

• Hepatic metabolism via CYP450 enzymes (notably CYP2D6)
• Renal excretion of unchanged drug
• Hydrolysis by plasma cholinesterases
• Excretion via bile without metabolism

Correct Answer: Hepatic metabolism via CYP450 enzymes (notably CYP2D6)

Q8. What is the approximate elimination half‑life of diphenhydramine in adults?

• Approximately 4–8 hours
• Less than 30 minutes
• 24–48 hours
• One week

Correct Answer: Approximately 4–8 hours

Q9. In severe central anticholinergic toxicity from diphenhydramine overdose, which antidote may be used?

• Physostigmine
• Naloxone
• Flumazenil
• Protamine sulfate

Correct Answer: Physostigmine

Q10. Diphenhydramine is contraindicated or should be avoided in which group?

• Newborns and premature infants
• Healthy young adults with seasonal allergies
• Adults with well‑controlled hypertension
• Patients receiving topical antifungals

Correct Answer: Newborns and premature infants

Q11. Which drug interaction is clinically important with diphenhydramine?

• Additive CNS depression with alcohol, benzodiazepines and opioids
• Marked reduction of ACE inhibitor efficacy
• Prevention of warfarin anticoagulation
• Inactivation of insulin

Correct Answer: Additive CNS depression with alcohol, benzodiazepines and opioids

Q12. Oral diphenhydramine typically begins to work within:

• 15–60 minutes after administration
• 24 hours after the first dose
• Immediately upon swallowing
• 3–5 days

Correct Answer: 15–60 minutes after administration

Q13. Which formulations of diphenhydramine are commonly available?

• Oral, topical and parenteral formulations (tablets, creams, injectables)
• Only inhaled powdered form
• Only sustained‑release transdermal patches
• Only ophthalmic injections

Correct Answer: Oral, topical and parenteral formulations (tablets, creams, injectables)

Q14. Many anticholinergic side effects of diphenhydramine arise from blockade of which receptors?

• Muscarinic acetylcholine receptors
• Nicotinic acetylcholine receptors at the neuromuscular junction
• Neuropeptide Y receptors
• Insulin receptors

Correct Answer: Muscarinic acetylcholine receptors

Q15. Diphenhydramine is useful for reducing symptoms of motion sickness primarily because of:

• Its anticholinergic (antiemetic) properties
• Its beta‑adrenergic blockade
• Inhibition of prostaglandin synthesis
• Direct stimulation of vestibular hair cells

Correct Answer: Its anticholinergic (antiemetic) properties

Q16. Regarding pregnancy, diphenhydramine is generally classified as:

• Pregnancy category B (use with caution)
• Contraindicated in all trimesters
• Known human teratogen
• Pregnancy category X

Correct Answer: Pregnancy category B (use with caution)

Q17. What is the recommendation for use of diphenhydramine during breastfeeding?

• Excreted in breast milk; use with caution or avoid in nursing infants
• Completely safe without any precautions
• Enhances milk production and is recommended
• Contraindicated because it permanently alters milk composition

Correct Answer: Excreted in breast milk; use with caution or avoid in nursing infants

Q18. Cardiovascular effect commonly seen with diphenhydramine due to anticholinergic activity is:

• Tachycardia
• Profound bradycardia in all patients
• Marked hypotension only in therapeutic doses
• Immediate myocardial infarction prevention

Correct Answer: Tachycardia

Q19. Diphenhydramine exhibits local anesthetic activity because it can:

• Block voltage‑gated sodium channels
• Activate opioid receptors on peripheral nerves
• Increase extracellular potassium to block conduction
• Directly sequester calcium ions in the synapse

Correct Answer: Block voltage‑gated sodium channels

Q20. With repeated use, which phenomenon regarding sedation may occur with diphenhydramine?

• Tolerance to sedative effects may develop
• Immediate sensitization causing increasing sedation each day
• Permanent loss of all sedative properties after one dose
• No change ever in sedative response with chronic dosing

Correct Answer: Tolerance to sedative effects may develop

Q21. A common adult oral dosing recommendation for diphenhydramine for allergic symptoms is:

• 25–50 mg every 4–6 hours as needed
• 0.5 mg once weekly
• 500 mg daily in a single dose
• 250 mg intramuscularly once a month

Correct Answer: 25–50 mg every 4–6 hours as needed

Q22. Pediatric safety: diphenhydramine should generally be avoided in children under:

• 2 years of age unless specifically directed by a physician
• 12 years of age only
• 6 months of age in all cases
• 18 years of age always

Correct Answer: 2 years of age unless specifically directed by a physician

Q23. The antihistamine effect of diphenhydramine is best described mechanistically as:

• Stabilizing inactive H1 receptor conformation (inverse agonism)
• Increasing histamine synthesis to desensitize receptors
• Irreversible receptor blockade by covalent binding
• Enhancing histamine release from mast cells

Correct Answer: Stabilizing inactive H1 receptor conformation (inverse agonism)

Q24. A primary metabolic reaction for diphenhydramine in the liver is:

• N‑demethylation to produce metabolites
• Direct glucuronide formation in plasma
• Reduction to a free radical intermediate
• Methylation at an aromatic ring to activate it

Correct Answer: N‑demethylation to produce metabolites

Q25. When dispensing diphenhydramine to elderly patients, pharmacists should monitor closely for:

• Confusion, urinary retention and increased fall risk
• Excessive salivation and muscle hypertrophy
• Hyperreflexia and weight gain
• Improved cognition and alertness

Correct Answer: Confusion, urinary retention and increased fall risk

Q26. Why is diphenhydramine commonly supplied as the hydrochloride salt?

• Hydrochloride salt increases water solubility for oral and parenteral use
• The salt makes it completely inactive until metabolized
• Salt formation prevents any CNS penetration
• Hydrochloride form is used only for topical antifungal activity

Correct Answer: Hydrochloride salt increases water solubility for oral and parenteral use

Q27. Co‑administration of diphenhydramine with MAO inhibitors can lead to:

• Potentiation of anticholinergic and sedative effects
• Complete antagonism of diphenhydramine activity
• Immediate renal clearance of both drugs
• Marked reduction in blood glucose

Correct Answer: Potentiation of anticholinergic and sedative effects

Q28. Diphenhydramine’s CNS effects compared to second‑generation antihistamines are:

• More central sedation because it is not peripherally selective and crosses the BBB
• Less sedating and strictly peripheral in action
• Completely devoid of any central activity
• Only active as a central stimulant

Correct Answer: More central sedation because it is not peripherally selective and crosses the BBB

Q29. Which acute movement disorder can be treated with diphenhydramine in clinical practice?

• Acute extrapyramidal dystonic reactions
• Chronic Parkinson’s disease motor decline as first‑line therapy
• Myasthenia gravis exacerbation
• Spinal cord transection

Correct Answer: Acute extrapyramidal dystonic reactions

Q30. How does diphenhydramine affect allergy skin testing?

• Can suppress skin‑test responses; discontinue 48–72 hours before testing
• Has no effect and need not be stopped before testing
• Enhances wheal formation, improving test sensitivity
• Replaces the need for skin testing entirely

Correct Answer: Can suppress skin‑test responses; discontinue 48–72 hours before testing

G S Sachin

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.

Mail- Sachin@pharmacyfreak.com