Hydantoins – Phenytoin MCQs With Answer

Hydantoins – Phenytoin MCQs With Answer

Hydantoins, especially phenytoin, are cornerstone antiepileptic agents studied in B. Pharm curricula due to their unique pharmacokinetics and clinical challenges. This introduction covers mechanism of action, therapeutic uses, absorption, hepatic metabolism (CYP2C9/2C19), zero-order kinetics, therapeutic drug monitoring, major adverse effects like gingival hyperplasia and teratogenicity, and common drug interactions. Understanding phenytoin’s dosing, toxicity signs (nystagmus, ataxia), and alternatives such as fosphenytoin is essential for safe patient care and rational dispensing. These MCQs emphasize application-level knowledge and exam-focused facts to strengthen your clinical and pharmacological grasp. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. Which is the primary mechanism of action of phenytoin?

• Enhancement of GABAergic inhibition
• Blockade of T-type calcium channels
• Stabilization of the inactive state of voltage-gated sodium channels
• Antagonism of NMDA receptors

Correct Answer: Stabilization of the inactive state of voltage-gated sodium channels

Q2. Phenytoin is most effective in treating which type of seizures?

• Absence seizures
• Generalized tonic-clonic and focal seizures
• Myoclonic seizures
• Infantile spasms

Correct Answer: Generalized tonic-clonic and focal seizures

Q3. Which pharmacokinetic property of phenytoin makes small dosage changes potentially produce large plasma concentration shifts?

• First-order elimination kinetics
• Zero-order (saturable) elimination at clinical concentrations
• Prolonged absorption half-life
• Extensive renal excretion of unchanged drug

Correct Answer: Zero-order (saturable) elimination at clinical concentrations

Q4. Which hepatic enzymes are primarily responsible for phenytoin metabolism?

• CYP3A4 and CYP1A2
• CYP2D6 and CYP3A5
• CYP2C9 and CYP2C19
• Monoamine oxidase (MAO)

Correct Answer: CYP2C9 and CYP2C19

Q5. What is the usual therapeutic total plasma concentration range for phenytoin?

• 1–5 µg/mL
• 5–10 µg/mL
• 10–20 µg/mL
• 30–50 µg/mL

Correct Answer: 10–20 µg/mL

Q6. Which early sign is most characteristic of phenytoin toxicity?

• Gingival bleeding
• Nystagmus
• Rash with epidermal detachment
• Excessive salivation

Correct Answer: Nystagmus

Q7. Long-term phenytoin therapy is commonly associated with which dental adverse effect?

• Aphthous ulcers
• Gingival hyperplasia
• Tooth erosion
• Pulpitis

Correct Answer: Gingival hyperplasia

Q8. Fosphenytoin differs from phenytoin mainly because it:

• Is more potent at GABA receptors
• Is a prodrug that is water-soluble and better tolerated IV/IM
• Has a longer half-life and is administered once a week
• Does not convert to phenytoin in vivo

Correct Answer: Is a prodrug that is water-soluble and better tolerated IV/IM

Q9. Which laboratory parameter should be monitored routinely in patients on long-term phenytoin therapy?

• Serum creatinine only
• Serum phenytoin (total and/or free), liver function tests, and CBC
• Serum amylase only
• Urine ketones

Correct Answer: Serum phenytoin (total and/or free), liver function tests, and CBC

Q10. In hypoalbuminemic patients, which measurement gives the most accurate phenytoin exposure?

• Total phenytoin concentration
• Corrected total concentration using Sheiner-Tozer equation
• Serum potassium concentration
• Urinary phenytoin excretion

Correct Answer: Corrected total concentration using Sheiner-Tozer equation

Q11. Which adverse effect is particularly associated with phenytoin use during pregnancy?

• Neonatal hypoglycemia
• Fetal hydantoin syndrome (craniofacial abnormalities, limb defects)
• Increased birth weight
• Enhanced fetal lung maturity

Correct Answer: Fetal hydantoin syndrome (craniofacial abnormalities, limb defects)

Q12. Which drug is known to decrease phenytoin plasma levels by inducing hepatic enzymes?

• Rifampicin
• Cimetidine
• Fluconazole
• Amiodarone

Correct Answer: Rifampicin

Q13. Which drug interaction can increase phenytoin levels and risk toxicity?

• Carbamazepine co-administration
• Valproic acid co-administration
• Rifampicin co-administration
• Phenobarbital co-administration

Correct Answer: Valproic acid co-administration

Q14. What cardiovascular risk is associated with rapid IV administration of phenytoin?

• Bradycardia and hypotension
• Hypertension and tachycardia
• Peripheral edema
• Deep vein thrombosis

Correct Answer: Bradycardia and hypotension

Q15. Which formulation excipient in IV phenytoin contributes to local pain and precipitation?

• Propylene glycol and ethanol vehicle
• Sodium chloride only
• Polyethylene glycol 400
• Sterile water alone

Correct Answer: Propylene glycol and ethanol vehicle

Q16. Phenytoin’s anticonvulsant activity is primarily due to its effect on:

• Increasing neuronal sodium channel opening frequency
• Reducing sustained high-frequency repetitive firing of neurons
• Blocking potassium channels to prolong action potentials
• Stimulating excitatory glutamate release

Correct Answer: Reducing sustained high-frequency repetitive firing of neurons

Q17. Which hematologic adverse effect can be seen with phenytoin therapy?

• Aplastic anemia in all patients
• Transient leukopenia, thrombocytopenia, or megaloblastic anemia
• Polycythemia vera
• Isolated eosinophilia only

Correct Answer: Transient leukopenia, thrombocytopenia, or megaloblastic anemia

Q18. Which clinical scenario is phenytoin NOT effective in treating?

• Generalized tonic-clonic seizures
• Focal seizures with secondary generalization
• Absence seizures
• Partial seizures

Correct Answer: Absence seizures

Q19. Which genetic polymorphism significantly affects phenytoin metabolism and dosage requirements?

• CYP2D6 ultra-rapid metabolizer variants
• CYP2C9 and CYP2C19 polymorphisms
• UGT1A1 polymorphism
• NAT2 slow acetylator status

Correct Answer: CYP2C9 and CYP2C19 polymorphisms

Q20. Which one best describes the Sheiner-Tozer correction for phenytoin in hypoalbuminemia?

• Corrected phenytoin = measured phenytoin × albumin (g/dL)
• Corrected phenytoin = measured phenytoin / (0.2 × albumin + 0.1)
• Corrected phenytoin = measured phenytoin − 5 µg/mL for albumin <3 g/dL
• There is no correction; free level measurement is impossible

Correct Answer: Corrected phenytoin = measured phenytoin / (0.2 × albumin + 0.1)

Q21. Which adverse dermatologic reaction is a serious but uncommon risk with phenytoin?

• Psoriasis
• Stevens-Johnson syndrome/toxic epidermal necrolysis
• Contact dermatitis only
• Acne vulgaris exclusively

Correct Answer: Stevens-Johnson syndrome/toxic epidermal necrolysis

Q22. Which vitamin deficiency is associated with chronic phenytoin therapy and contributes to osteomalacia?

• Vitamin C deficiency
• Vitamin D and folate deficiency
• Vitamin B12 excess
• Vitamin K deficiency only

Correct Answer: Vitamin D and folate deficiency

Q23. Which statement about phenytoin absorption is correct?

• Phenytoin has 100% oral bioavailability and immediate absorption
• Oral absorption is variable; suspension and capsule formulations differ in rate
• It is absorbed only when taken with a fatty meal
• It is administered sublingually for best effect

Correct Answer: Oral absorption is variable; suspension and capsule formulations differ in rate

Q24. Which monitoring is most useful to detect early phenytoin neurotoxicity?

• Periodic ECG alone
• Clinical monitoring for nystagmus, ataxia, and cognitive changes
• Urine drug screening
• Serum sodium levels only

Correct Answer: Clinical monitoring for nystagmus, ataxia, and cognitive changes

Q25. Which drug will most likely have reduced contraceptive efficacy when co-administered with phenytoin?

• Levonorgestrel IUD
• Combined oral contraceptive pills (ethinylestradiol + progestin)
• Depot medroxyprogesterone acetate (injectable)
• Non-hormonal copper IUD

Correct Answer: Combined oral contraceptive pills (ethinylestradiol + progestin)

Q26. Which electrolyte disturbance can be caused or exacerbated by anticonvulsants like phenytoin?

• Hyperkalemia
• Hyponatremia (more commonly with carbamazepine, less with phenytoin)
• Hypercalcemia
• Hypophosphatemia only

Correct Answer: Hyponatremia (more commonly with carbamazepine, less with phenytoin)

Q27. Which of the following is a contraindication to rapid IV infusion of phenytoin?

• Hypotension and heart block
• Well-controlled tonic-clonic seizures
• Use of oral phenytoin
• Stable liver function

Correct Answer: Hypotension and heart block

Q28. Which metabolic clearance characteristic best applies to phenytoin at therapeutic concentrations?

• Clearance increases linearly with dose
• Clearance is constant due to renal elimination
• Clearance becomes saturated, following Michaelis-Menten kinetics
• Clearance is independent of enzyme activity

Correct Answer: Clearance becomes saturated, following Michaelis-Menten kinetics

Q29. Which clinical use is phenytoin commonly indicated for in emergency settings?

• Management of status epilepticus after benzodiazepines
• Treatment of febrile seizures in infants as first-line
• Immediate control of absence status
• Acute management of cluster headaches

Correct Answer: Management of status epilepticus after benzodiazepines

Q30. Which organ system toxicity requires periodic monitoring during chronic phenytoin therapy?

• Pulmonary function tests
• Liver function tests (hepatotoxicity risk)
• Visual acuity only
• Pancreatic enzyme levels routinely

Correct Answer: Liver function tests (hepatotoxicity risk)

Q31. Which drug is NOT a typical inducer of phenytoin metabolism?

• Carbamazepine
• Phenobarbital
• Rifampicin
• Fluoxetine

Correct Answer: Fluoxetine

Q32. The free (unbound) fraction of phenytoin is increased in which condition?

• Hyperalbuminemia
• Hypoalbuminemia
• High plasma pH only
• Presence of strong base co-medication only

Correct Answer: Hypoalbuminemia

Q33. Which clinical sign suggests chronic cerebellar toxicity from phenytoin?

• Resting tremor
• Intention tremor and ataxia
• Brisk deep tendon reflexes only
• Muscle hypertrophy

Correct Answer: Intention tremor and ataxia

Q34. Which statement about phenytoin and pregnancy is correct?

• Phenytoin is completely safe and requires no monitoring in pregnancy
• Phenytoin carries teratogenic risk and dosing/levels should be closely monitored
• It prevents all fetal malformations when supplemented with folate
• Phenytoin is contraindicated in men planning fatherhood only

Correct Answer: Phenytoin carries teratogenic risk and dosing/levels should be closely monitored

Q35. Which of the following is a pharmacodynamic interaction of phenytoin?

• Phenytoin increases clearance of warfarin
• Phenytoin and benzodiazepines both depress CNS, increasing sedation
• Phenytoin induces hepatic enzymes
• Phenytoin displaces bilirubin from albumin

Correct Answer: Phenytoin and benzodiazepines both depress CNS, increasing sedation

Q36. Which adverse metabolic effect is sometimes seen with long-term phenytoin use?

• Hyperthyroidism
• Decreased bone mineral density leading to osteomalacia
• Increase in HDL cholesterol only
• Hypervitaminosis D

Correct Answer: Decreased bone mineral density leading to osteomalacia

Q37. Which is TRUE regarding IV phenytoin compatibility?

• IV phenytoin is compatible with all IV fluids and antibiotics
• IV phenytoin may precipitate with certain solutions; flushing and separate lines are recommended
• It can be mixed with dextrose-containing solutions without risk
• Phenytoin should be heated before administration to avoid precipitation

Correct Answer: IV phenytoin may precipitate with certain solutions; flushing and separate lines are recommended

Q38. Which adverse cosmetic effect is commonly reported with phenytoin?

• Skin lightening
• Hirsutism (excessive hair growth)
• Alopecia exclusively
• Vitiligo

Correct Answer: Hirsutism (excessive hair growth)

Q39. Which statement about phenytoin’s effect on other drugs is correct?

• Phenytoin inhibits CYP enzymes, increasing levels of many drugs
• Phenytoin induces CYP enzymes, reducing plasma levels of many drugs
• Phenytoin has no clinically significant interactions
• Phenytoin always increases anticoagulant effect of warfarin

Correct Answer: Phenytoin induces CYP enzymes, reducing plasma levels of many drugs

Q40. Which is the reason to measure free phenytoin concentration rather than total in certain patients?

• Free concentration is less relevant pharmacologically
• Total concentration is always accurate regardless of albumin
• In hypoalbuminemia or with drugs that displace protein, free level correlates with effect/toxicity
• Free concentration cannot be measured clinically

Correct Answer: In hypoalbuminemia or with drugs that displace protein, free level correlates with effect/toxicity

Q41. Which medication is often used as an alternative to phenytoin in status epilepticus when cardiovascular compromise is a concern?

• Phenobarbital oral
• Fosphenytoin (IV) or levetiracetam IV
• Carbamazepine oral
• Ethosuximide IV

Correct Answer: Fosphenytoin (IV) or levetiracetam IV

Q42. Which laboratory test should be considered before initiating phenytoin in a patient with suspected hepatic disease?

• Thyroid function tests
• Liver function tests (AST, ALT, bilirubin)
• Fasting glucose only
• Urine culture

Correct Answer: Liver function tests (AST, ALT, bilirubin)

Q43. Which formulation of phenytoin provides more predictable absorption for chronic therapy?

• Immediate-release suspension only
• Extended or controlled release formulations and careful dosing monitoring
• Sublingual tablets
• Rectal suppositories exclusively

Correct Answer: Extended or controlled release formulations and careful dosing monitoring

Q44. Which metabolic pathway alteration is most likely to increase phenytoin half-life and levels?

• Induction of CYP2C9
• Inhibition of CYP2C9 (e.g., by fluconazole)
• Enhanced renal clearance
• Administration with vitamin C

Correct Answer: Inhibition of CYP2C9 (e.g., by fluconazole)

Q45. Which statement about phenytoin dosing is correct?

• Phenytoin dosing is linear so doubling the dose doubles the level always
• Dosing must be individualized with small changes due to nonlinear kinetics
• Children and adults require the same mg/kg dosages with identical kinetics
• No therapeutic monitoring is needed once dose stabilized

Correct Answer: Dosing must be individualized with small changes due to nonlinear kinetics

Q46. Which drug combination requires caution because phenytoin may reduce the effectiveness of the co-medication?

• Phenytoin with oral contraceptive pills
• Phenytoin with acetaminophen (paracetamol)
• Phenytoin with insulin
• Phenytoin with topical antifungal cream

Correct Answer: Phenytoin with oral contraceptive pills

Q47. Which side effect is dose-related and reversible on dose reduction or discontinuation?

• Gingival hyperplasia
• Phenytoin-induced nystagmus and ataxia
• Teratogenic skeletal defects
• Chronic cosmetic changes like hirsutism

Correct Answer: Phenytoin-induced nystagmus and ataxia

Q48. For which patient condition is monitoring free phenytoin concentration especially recommended?

• Patients with normal albumin and no comedications
• Patients with renal failure and hypoalbuminemia or on interacting drugs
• Patients taking only topical medications
• Patients with stable, long-term therapy without symptoms

Correct Answer: Patients with renal failure and hypoalbuminemia or on interacting drugs

Q49. Which contraceptive counseling point is important for women taking phenytoin?

• No special counseling is needed
• Use additional or alternative non-enzyme-inducing contraception because phenytoin can reduce oral contraceptive efficacy
• Phenytoin enhances the effect of oral contraceptives so doses should be reduced
• Only natural family planning is effective

Correct Answer: Use additional or alternative non-enzyme-inducing contraception because phenytoin can reduce oral contraceptive efficacy

Q50. Which counseling point should a B. Pharm student emphasize about phenytoin therapy to patients?

• Missed doses can be doubled next time to catch up
• Report signs of toxicity (nystagmus, ataxia), maintain dental hygiene, and avoid abrupt withdrawal
• Phenytoin is safe to stop abruptly if seizures stop
• Alcohol has no interaction with phenytoin

Correct Answer: Report signs of toxicity (nystagmus, ataxia), maintain dental hygiene, and avoid abrupt withdrawal

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