Miscellaneous anticonvulsants – Valproic acid MCQs With Answer

Miscellaneous anticonvulsants – Valproic acid MCQs With Answer

Valproic acid is a cornerstone miscellaneous anticonvulsant important in seizure management, bipolar disorder and migraine prophylaxis. This concise introduction for B. Pharm students highlights essential pharmacology: mechanism of action (GABAergic enhancement, sodium and T‑type calcium channel blockade), pharmacokinetics, metabolism, therapeutic range, formulations (valproic acid, sodium valproate, divalproex), dose adjustment, major adverse effects (hepatotoxicity, teratogenicity, pancreatitis, hyperammonemia, thrombocytopenia), and clinically important drug interactions and monitoring. Understanding laboratory monitoring, risk factors and toxicity management (L‑carnitine, supportive care) is vital for safe dispensing and counseling. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. Which is the primary biochemical mechanism by which valproic acid exerts its anticonvulsant effect?

• Inhibition of GABA transaminase leading to increased GABA levels
• Selective antagonism of NMDA receptors
• Potent agonism at benzodiazepine receptors
• Inhibition of monoamine oxidase

Correct Answer: Inhibition of GABA transaminase leading to increased GABA levels

Q2. Valproic acid also contributes to seizure control by which additional actions?

• Blocking voltage‑gated sodium channels and T‑type calcium channels
• Increasing glutamate release
• Inhibiting GABA synthesis
• Enhancing opioid receptor activity

Correct Answer: Blocking voltage‑gated sodium channels and T‑type calcium channels

Q3. Which formulation is a coordinated salt designed to improve gastrointestinal tolerability and allow dosing flexibility?

• Divalproex sodium
• Valproic acid sodium salt
• Valproate magnesium
• Valproate potassium

Correct Answer: Divalproex sodium

Q4. Which clinical indication is NOT commonly treated with valproic acid?

• Generalized tonic‑clonic seizures
• Absence seizures (first‑line is ethosuximide, but valproate is effective)
• Bipolar disorder (acute mania)
• Acute bacterial meningitis

Correct Answer: Acute bacterial meningitis

Q5. What is the usual therapeutic plasma concentration range for total valproic acid when monitoring for anticonvulsant effect?

• 50–100 µg/mL
• 5–15 µg/mL
• 200–400 µg/mL
• 0.5–2 µg/mL

Correct Answer: 50–100 µg/mL

Q6. Which laboratory test is most important to monitor prior to and during long‑term valproic acid therapy?

• Liver function tests (ALT, AST)
• Serum amylase only once
• Urine culture
• Thyroid stimulating hormone monthly

Correct Answer: Liver function tests (ALT, AST)

Q7. Valproic acid is associated with which serious hematologic adverse effect that requires periodic monitoring?

• Thrombocytopenia
• Agranulocytosis exclusively
• Hemolytic anemia only in neonates
• Polycythemia vera

Correct Answer: Thrombocytopenia

Q8. Which patient population is at highest risk for fatal hepatotoxicity from valproic acid?

• Young children under 2 years, especially with metabolic disorders or on polytherapy
• Healthy adults aged 30–40 on monotherapy
• Elderly patients with hypertension only
• Adolescents on monotherapy with normal labs

Correct Answer: Young children under 2 years, especially with metabolic disorders or on polytherapy

Q9. Which adverse effect is characteristically teratogenic and strongly linked to valproic acid exposure during pregnancy?

• Neural tube defects (e.g., spina bifida)
• Congenital cataracts only
• Postnatal growth hormone deficiency
• Situs inversus

Correct Answer: Neural tube defects (e.g., spina bifida)

Q10. Regarding pregnancy, current guidance for valproic acid states:

• Avoid valproate in women of childbearing potential unless no suitable alternative exists
• Valproate is safe throughout pregnancy with folate supplementation only
• Valproate is first‑line for pregnancy epilepsy prophylaxis
• Valproate reduces teratogenic risk compared to carbamazepine

Correct Answer: Avoid valproate in women of childbearing potential unless no suitable alternative exists

Q11. Which laboratory finding may indicate valproate‑induced hyperammonemic encephalopathy even if LFTs are normal?

• Elevated plasma ammonia (hyperammonemia)
• Low serum sodium only
• Isolated elevated creatinine kinase
• Hypoglycemia without other abnormalities

Correct Answer: Elevated plasma ammonia (hyperammonemia)

Q12. A patient on valproate develops acute pancreatitis. Which is the appropriate recognition about this adverse effect?

• Pancreatitis is a known rare but serious adverse event associated with valproate
• Pancreatitis is impossible with valproate; look for other causes only
• Pancreatitis always occurs only after years of therapy
• Pancreatitis is prevented by concomitant carbamazepine

Correct Answer: Pancreatitis is a known rare but serious adverse event associated with valproate

Q13. Which interaction is clinically important when valproate is coadministered with lamotrigine?

• Valproate inhibits lamotrigine glucuronidation and increases lamotrigine levels
• Valproate induces lamotrigine metabolism decreasing its levels
• Lamotrigine increases valproate clearance via CYP3A4 induction
• There is no interaction between valproate and lamotrigine

Correct Answer: Valproate inhibits lamotrigine glucuronidation and increases lamotrigine levels

Q14. How does hypoalbuminemia affect interpretation of valproic acid levels?

• Total valproate may be low while free (active) fraction is elevated — measure free level if needed
• Hypoalbuminemia always lowers free valproate levels
• Albumin changes do not affect valproate binding or levels
• Total levels are sufficient regardless of albumin status

Correct Answer: Total valproate may be low while free (active) fraction is elevated — measure free level if needed

Q15. Which enzyme pathway primarily metabolizes valproic acid?

• Hepatic metabolism including glucuronidation and mitochondrial β‑oxidation
• Renal excretion unchanged only
• Primary metabolism by plasma esterases
• Metabolism exclusively via CYP3A4 oxidation

Correct Answer: Hepatic metabolism including glucuronidation and mitochondrial β‑oxidation

Q16. In cases of severe valproate‑induced hyperammonemia or hepatotoxicity, which adjunctive treatment is recommended?

• L‑carnitine supplementation
• Phenytoin infusion
• High‑dose vitamin K only
• Immediate long‑term corticosteroids

Correct Answer: L‑carnitine supplementation

Q17. Which monitoring is indicated during the first 6 months of valproate therapy?

• Baseline and periodic LFTs, CBC (platelet count), and clinical assessment for signs of toxicity
• No monitoring is necessary for the first year
• Only ECG monitoring is required monthly
• Bone density scans monthly

Correct Answer: Baseline and periodic LFTs, CBC (platelet count), and clinical assessment for signs of toxicity

Q18. Which statement about valproic acid protein binding is correct?

• Valproate is highly protein bound (~90%), and free fraction increases in overdose or hypoalbuminemia
• Valproate is not protein bound at all
• Protein binding is negligible and clinically unimportant
• Valproate binds exclusively to hemoglobin

Correct Answer: Valproate is highly protein bound (~90%), and free fraction increases in overdose or hypoalbuminemia

Q19. What is a common cosmetic adverse effect of valproate that may be reversible on discontinuation?

• Alopecia (hair loss)
• Permanent alopecia in every patient
• Severe skin hyperpigmentation only
• Complete tooth enamel loss

Correct Answer: Alopecia (hair loss)

Q20. Which metabolic endocrine disturbance is associated with long‑term valproate therapy in women?

• Polycystic ovary syndrome (weight gain, hyperandrogenism, menstrual irregularities)
• Type I diabetes mellitus exclusively
• Primary hypothyroidism only
• Adrenal insufficiency only

Correct Answer: Polycystic ovary syndrome (weight gain, hyperandrogenism, menstrual irregularities)

Q21. Which medication combination increases risk of valproate toxicity by displacement from plasma proteins or metabolic interactions?

• Phenytoin — valproate can displace and interact leading to altered free levels
• Vitamin C — ascorbic acid neutralizes valproate
• Paracetamol — always decreases valproate toxicity
• Topical steroid cream — major systemic interaction

Correct Answer: Phenytoin — valproate can displace and interact leading to altered free levels

Q22. Which statement about valproic acid half‑life is correct?

• Elimination half‑life is variable (9–16 hours in adults) and may be prolonged in overdose or hepatic impairment
• Half‑life is consistently 1 hour in all patients
• Half‑life is >7 days normally
• Valproate has no measurable half‑life

Correct Answer: Elimination half‑life is variable (9–16 hours in adults) and may be prolonged in overdose or hepatic impairment

Q23. Which overdose management option may be considered for severe valproate toxicity?

• Hemodialysis in severe life‑threatening overdose
• Immediate administration of sodium bicarbonate for alkalinization only
• Exchange transfusion as first‑line in all cases
• No intervention is available for severe overdose

Correct Answer: Hemodialysis in severe life‑threatening overdose

Q24. Which of the following best describes the effect of enzyme inducers (e.g., carbamazepine) on valproate levels?

• Enzyme inducers can increase valproate metabolism and reduce its plasma concentration
• They always increase valproate levels by inhibiting clearance
• They have no effect on valproate pharmacokinetics
• They convert valproate into a more active form

Correct Answer: Enzyme inducers can increase valproate metabolism and reduce its plasma concentration

Q25. For acute manic episodes in bipolar disorder, valproate dosing typically starts at which relative level?

• Initial loading or starting doses around 10–15 mg/kg/day, titrating upward as needed
• Single 1 g dose only once with no maintenance
• Very low dose of 0.1 mg/kg/day
• Only topical application is recommended

Correct Answer: Initial loading or starting doses around 10–15 mg/kg/day, titrating upward as needed

Q26. Which statement about valproic acid and mitochondrial function is accurate?

• Valproate interferes with mitochondrial β‑oxidation and can precipitate mitochondrial toxicity in susceptible patients
• Valproate enhances mitochondrial β‑oxidation and protects mitochondria
• Valproate exclusively affects only nuclear DNA and not mitochondria
• Valproate has no known actions related to mitochondria

Correct Answer: Valproate interferes with mitochondrial β‑oxidation and can precipitate mitochondrial toxicity in susceptible patients

Q27. Which sign should prompt immediate evaluation for valproate‑related hepatic failure?

• Jaundice, persistent vomiting, lethargy, or marked transaminase elevation
• Mild headache relieved by rest
• Transient increase in appetite only
• Intermittent sneezing

Correct Answer: Jaundice, persistent vomiting, lethargy, or marked transaminase elevation

Q28. Which of the following is TRUE about valproate use in absence seizures?

• Valproate is effective and commonly used for generalized absence seizures
• Valproate has no efficacy in absence seizures
• Valproate exacerbates absence seizures in all patients
• Valproate is contraindicated with ethosuximide

Correct Answer: Valproate is effective and commonly used for generalized absence seizures

Q29. Which lab abnormality warrants dose reduction or discontinuation of valproate?

• Markedly elevated transaminases or clinically significant hepatotoxicity
• Mild transient dizziness without lab changes
• Well‑controlled seizures without adverse effects
• Minor injection site itching

Correct Answer: Markedly elevated transaminases or clinically significant hepatotoxicity

Q30. Which monitoring is useful when a patient on valproate shows cognitive decline and confusion suggesting encephalopathy?

• Plasma ammonia level
• Serum potassium only
• Urinalysis exclusively
• Serum triglycerides only

Correct Answer: Plasma ammonia level

Q31. Which description best fits valproate’s pregnancy risk classification and counseling point?

• Valproate has a high teratogenic risk and is generally discouraged during pregnancy
• Valproate is safe and recommended as first‑line in pregnancy
• Valproate poses no fetal risk when combined with folate
• Valproate increases fertility and reduces fetal risk

Correct Answer: Valproate has a high teratogenic risk and is generally discouraged during pregnancy

Q32. Which clinical use of valproate is NOT an anticonvulsant indication but an approved psychiatric indication?

• Acute mania in bipolar disorder
• Schizophrenia as monotherapy for psychosis
• Primary treatment for ADHD only
• Prophylaxis of bacterial infections

Correct Answer: Acute mania in bipolar disorder

Q33. Which adverse hematologic effect is commonly monitored and can necessitate dose adjustment of valproate?

• Decrease in platelet count (thrombocytopenia)
• Persistent high white cell count always requiring discontinuation
• Sustained increase in hemoglobin to polycythemic levels
• Elevated eosinophils exclusively

Correct Answer: Decrease in platelet count (thrombocytopenia)

Q34. Which statement about interaction with warfarin is correct when coadministered with valproate?

• Valproate can potentiate warfarin effect and increase INR — monitor closely
• Valproate has no interaction with warfarin
• Valproate decreases warfarin anticoagulant effect always
• Valproate neutralizes warfarin leading to clotting

Correct Answer: Valproate can potentiate warfarin effect and increase INR — monitor closely

Q35. Which statement about therapeutic drug monitoring (TDM) of valproate is correct?

• Measure trough total and consider free levels for hypoalbuminemia or severe illness
• Random levels are always sufficient and timing is irrelevant
• Serum monitoring is unnecessary because clinical response is the only guide
• Only urinary valproate measurement is clinically useful

Correct Answer: Measure trough total and consider free levels for hypoalbuminemia or severe illness

Q36. Which adverse metabolic effect is commonly associated with valproate therapy?

• Weight gain and metabolic syndrome features
• Marked weight loss in all patients
• Rapid muscle wasting always
• Decreased appetite with malnutrition exclusively

Correct Answer: Weight gain and metabolic syndrome features

Q37. Which statement best describes valproate’s effect on CYP enzymes?

• Valproate is a modest inhibitor of certain enzymes (e.g., UGT, some CYPs), leading to drug interactions
• Valproate is a potent universal CYP inducer
• Valproate has no effect on hepatic enzymes
• Valproate irreversibly activates CYP450 enzymes

Correct Answer: Valproate is a modest inhibitor of certain enzymes (e.g., UGT, some CYPs), leading to drug interactions

Q38. Which advice is appropriate when dispensing valproate to women of childbearing potential?

• Discuss teratogenic risks, use effective contraception, and consider alternatives where possible
• No counseling is necessary for contraception or pregnancy risks
• Tell them valproate improves fetal neural development
• Advise stopping contraception when starting valproate

Correct Answer: Discuss teratogenic risks, use effective contraception, and consider alternatives where possible

Q39. When converting from oral valproic acid to intravenous formulation, which is true?

• Intravenous valproate preparations are available and dosage is adjusted to provide equivalent plasma exposure
• Oral valproate and IV valproate are not bioequivalent and cannot be interchanged
• IV valproate is ineffective compared with oral
• IV valproate causes guaranteed hepatotoxicity

Correct Answer: Intravenous valproate preparations are available and dosage is adjusted to provide equivalent plasma exposure

Q40. In a patient with renal impairment, how should valproate dosing generally be approached?

• Most valproate is hepatically metabolized; use caution but dosing often requires less adjustment than purely renally excreted drugs
• Valproate is contraindicated in any renal impairment
• Increase dose substantially because clearance is faster
• No monitoring is ever needed in renal impairment

Correct Answer: Most valproate is hepatically metabolized; use caution but dosing often requires less adjustment than purely renally excreted drugs

Q41. Which clinical sign may indicate valproate‑associated hyperammonemic encephalopathy?

• Somnolence, confusion, vomiting, and decreased level of consciousness
• Isolated hypertension only
• Increased visual acuity
• Excessive hair growth only

Correct Answer: Somnolence, confusion, vomiting, and decreased level of consciousness

Q42. Which drug when coadministered may require valproate dose reduction due to additive hematologic toxicity?

• Carbamazepine — may produce additive hematologic adverse effects and complex interactions
• Folic acid — increases valproate toxicity dramatically
• Topical antibiotics — systemic interaction is certain
• Vitamin D — causes valproate accumulation

Correct Answer: Carbamazepine — may produce additive hematologic adverse effects and complex interactions

Q43. Which metabolic tracing explains valproate‑related hyperammonemia?

• Valproate impairs urea cycle function and mitochondrial metabolism, leading to accumulation of ammonia
• Valproate enhances urea cycle clearance of ammonia exclusively
• Valproate prevents ammonia production entirely
• Valproate causes ammonia to be excreted via lungs

Correct Answer: Valproate impairs urea cycle function and mitochondrial metabolism, leading to accumulation of ammonia

Q44. Which adverse effect should be listed on a patient information leaflet for valproate?

• Potential for birth defects and cognitive impairment in exposed fetuses
• Guaranteed improvement in fertility
• Absence of any liver or pancreatic effects
• No interaction with alcohol at all

Correct Answer: Potential for birth defects and cognitive impairment in exposed fetuses

Q45. Which of the following is an appropriate counseling point for patients starting valproate?

• Report signs of jaundice, unexplained bruising, severe abdominal pain, or altered mental status immediately
• No need to report any symptoms; valproate has no serious side effects
• Stop valproate abruptly if you miss one dose and then double the next dose
• Valproate cures epilepsy permanently after one month

Correct Answer: Report signs of jaundice, unexplained bruising, severe abdominal pain, or altered mental status immediately

Q46. Which of the following best describes valproate’s effect on platelet function?

• Valproate can reduce platelet count and affect platelet aggregation, increasing bleeding risk
• Valproate increases platelet count and causes thrombosis
• Valproate has no effect on platelets
• Valproate only improves platelet function in liver disease

Correct Answer: Valproate can reduce platelet count and affect platelet aggregation, increasing bleeding risk

Q47. Which drug interaction may lead to increased valproate concentration due to inhibition of valproate metabolism?

• Felbamate or drugs that inhibit glucuronidation may increase valproate levels
• Rifampicin — inhibits valproate directly increasing levels
• St. John’s Wort — always increases valproate levels
• Metformin — inhibits valproate clearance and raises levels

Correct Answer: Felbamate or drugs that inhibit glucuronidation may increase valproate levels

Q48. Which statement about valproate dosing in pediatric patients is correct?

• Pediatric dosing is weight‑based and careful monitoring for hepatotoxicity is essential, especially under 2 years
• Children require the same fixed adult dose regardless of weight
• Valproate is never used in children
• Pediatric dosing is always lower than 0.1 mg/kg/day

Correct Answer: Pediatric dosing is weight‑based and careful monitoring for hepatotoxicity is essential, especially under 2 years

Q49. Which clinical scenario indicates consideration of measuring free (unbound) valproate concentration?

• Hypoalbuminemia, renal failure, pregnancy, or severe illness where protein binding is altered
• Young healthy adult with normal albumin and no comorbidities
• Routine monitoring always uses urine free valproate exclusively
• Only when using topical valproate

Correct Answer: Hypoalbuminemia, renal failure, pregnancy, or severe illness where protein binding is altered

Q50. Which management step is recommended if a patient on valproate develops severe elevation in transaminases?

• Discontinue valproate immediately and evaluate for hepatic failure; consider alternative therapy
• Continue valproate without change and reassess in one year
• Double the dose to overcome transaminase elevation
• Ignore transaminase elevations unless bilirubin rises

Correct Answer: Discontinue valproate immediately and evaluate for hepatic failure; consider alternative therapy

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