A 30-year-old man with focal epilepsy takes phenytoin 300 mg/day; his trough level is 8 µg/mL (therapeutic 10-20 µg/mL) and seizures continue. The dose is raised to 400 mg/day. Three weeks later he has nystagmus and an unsteady gait, and the level is 28 µg/mL. Why did a one-third dose increase more than triple the level?

Saturation of its liver enzymes

It is displaced from plasma albumin

Its absorption rises at higher doses

A 30-year-old woman on the NTEP regimen for pulmonary TB, who was not given pyridoxine, develops burning and tingling in both feet after two months. Her brother, on the same regimen, has no symptoms. Which inherited difference most likely explains why she developed this adverse effect?

Slow acetylation by N-acetyltransferase 2

Deficiency of pseudocholinesterase

Deficiency of G6PD in red cells

Why is probenecid sometimes given together with penicillin?

It blocks tubular secretion of penicillin

It increases oral absorption of penicillin

It inhibits hepatic metabolism of penicillin

It inhibits bacterial beta-lactamase

A 24-year-old woman with epilepsy on sodium valproate is started on lamotrigine as add-on therapy, titrated as for a patient on no other antiepileptic. Three weeks later she has fever, mucosal erosions and a spreading blistering rash. Why should lamotrigine have been started at a lower dose in her?

Valproate inhibits lamotrigine glucuronidation

Valproate induces lamotrigine metabolism

Valproate blocks renal excretion of lamotrigine

Valproate displaces lamotrigine from albumin

Pharmacokinetics, pharmacodynamics and drug interactions

23 NEET-PG practice questions on Pharmacokinetics, pharmacodynamics and drug interactions, part of Pharmacology. The first 23 are below; the first 5 with answers and explanations (tap Show answer after you have chosen), the rest in Learn with a free account.

Question 1 · Medium
A 30-year-old man with focal epilepsy takes phenytoin 300 mg/day; his trough level is 8 µg/mL (therapeutic 10-20 µg/mL) and seizures continue. The dose is raised to 400 mg/day. Three weeks later he has nystagmus and an unsteady gait, and the level is 28 µg/mL. Why did a one-third dose increase more than triple the level?
1. AIt is displaced from plasma albumin
2. BSaturation of its liver enzymes
3. CIt induces its own metabolism
4. DIts absorption rises at higher doses
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Answer: B · Saturation of its liver enzymes
Phenytoin is cleared by liver enzymes that saturate within the therapeutic range, so elimination shifts from first-order to zero-order (Michaelis-Menten) kinetics. Once saturated, a fixed amount is removed per unit time and any further dose increase raises the level disproportionately, with a longer half-life. Doses should be raised in small steps with level monitoring. Nystagmus, then ataxia, then drowsiness appear as levels climb above the range.
- A: Displacement raises the free fraction transiently, not the total level threefold.
- C: Auto-induction, as with carbamazepine, would lower levels over time, not raise them.
- D: Absorption does not explain it; the problem is limited elimination.
Question 2 · Medium
A 30-year-old woman on the NTEP regimen for pulmonary TB, who was not given pyridoxine, develops burning and tingling in both feet after two months. Her brother, on the same regimen, has no symptoms. Which inherited difference most likely explains why she developed this adverse effect?
1. ASlow acetylation by N-acetyltransferase 2
2. BDeficiency of pseudocholinesterase
3. CDeficiency of G6PD in red cells
4. DReduced activity of CYP2C19
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Answer: A · Slow acetylation by N-acetyltransferase 2
Isoniazid is inactivated by acetylation through NAT2, which shows a genetic polymorphism; slow acetylators keep higher levels for longer. Isoniazid causes pyridoxine depletion, and slow acetylators are more prone to peripheral neuropathy. Pyridoxine supplementation prevents it and is given with isoniazid in the national programme. Slow acetylators are also more prone to hydralazine- and procainamide-induced lupus.
- B: Pseudocholinesterase deficiency causes prolonged apnoea after succinylcholine.
- C: G6PD deficiency causes haemolysis with oxidant drugs, not neuropathy.
- D: CYP2C19 polymorphism affects clopidogrel and proton pump inhibitors, not isoniazid.
Question 3 · Easy
Why is probenecid sometimes given together with penicillin?
1. AIt increases oral absorption of penicillin
2. BIt inhibits hepatic metabolism of penicillin
3. CIt inhibits bacterial beta-lactamase
4. DIt blocks tubular secretion of penicillin
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Answer: D · It blocks tubular secretion of penicillin
Penicillins are eliminated mainly by active secretion through the organic anion transporters of the proximal tubule. Probenecid competes for these transporters, so penicillin is excreted more slowly and its plasma level stays higher for longer. This interaction is used deliberately to prolong the action of some beta-lactams. Probenecid itself is a uricosuric drug.
- A: Probenecid does not change gut absorption of penicillin.
- B: Penicillin is not cleared mainly by hepatic metabolism.
- C: Beta-lactamase inhibitors are drugs such as clavulanic acid, not probenecid.
Question 4 · Hard
A 55-year-old man with COPD who smokes 20 cigarettes a day is to be started on oral theophylline. His theophylline clearance is estimated at 4 L/h, oral bioavailability is taken as 100% and the target steady-state level is 10 mg/L. What dose should be given every 12 hours?
1. A240 mg
2. B960 mg
3. C480 mg
4. D40 mg
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Answer: C · 480 mg
Maintenance dose rate = clearance x target concentration / bioavailability = 4 L/h x 10 mg/L / 1 = 40 mg/h. Every 12 hours this is 40 x 12 = 480 mg. Smoking induces CYP1A2, which raises theophylline clearance, so smokers need larger doses; if he stops smoking, clearance falls and the dose must be cut to avoid toxicity. Levels should be checked once steady state is reached.
- A: 240 mg is the dose for a 6-hour interval.
- B: 960 mg is the dose for a full 24 hours.
- D: 40 mg is the hourly dose rate, not the 12-hourly dose.
Question 5 · Medium
A 24-year-old woman with epilepsy on sodium valproate is started on lamotrigine as add-on therapy, titrated as for a patient on no other antiepileptic. Three weeks later she has fever, mucosal erosions and a spreading blistering rash. Why should lamotrigine have been started at a lower dose in her?
1. AValproate induces lamotrigine metabolism
2. BValproate inhibits lamotrigine glucuronidation
3. CValproate blocks renal excretion of lamotrigine
4. DValproate displaces lamotrigine from albumin
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Answer: B · Valproate inhibits lamotrigine glucuronidation
Lamotrigine is cleared mainly by glucuronidation, which valproate inhibits, roughly doubling its half-life and plasma level. The risk of serious rash, including Stevens-Johnson syndrome, rises with high starting doses and fast titration, so with valproate lamotrigine is started lower and increased more slowly. This patient's features suggest SJS, and lamotrigine must be stopped at once. Enzyme inducers such as carbamazepine have the opposite effect and need higher lamotrigine doses.
- A: Induction would lower lamotrigine levels and need higher, not lower, doses.
- C: Lamotrigine is cleared by hepatic glucuronidation, not mainly by renal excretion.
- D: Protein-binding displacement is not the clinically important mechanism here.
Question 6 · Medium
A 45-year-old man with ulcerative colitis has been maintained on azathioprine 100 mg/day. At a private clinic he is started on allopurinol 300 mg/day for gout. Four weeks later he has fever and mouth ulcers; TLC is 1,200/µL and platelets 40,000/µL. What explains the marrow suppression?
1. AInduction of TPMT increasing toxic metabolites
2. BAdditive marrow toxicity of allopurinol itself
3. CXanthine oxidase inhibition blocking 6-mercaptopurine breakdown
4. DAllopurinol hypersensitivity syndrome
Answer and explanation in LearnFree account
Question 7 · Hard
A 50-year-old man stable on lithium for bipolar disorder for six years develops tremor, ataxia and confusion. In the last month new drugs have been started by different doctors. Which of these drugs can raise his serum lithium level? 1. Hydrochlorothiazide for hypertension 2. Enalapril for proteinuria 3. Diclofenac for knee pain 4. Theophylline for COPD
1. A3 and 4 only
2. B1 and 2 only
3. C1, 2 and 3 only
4. D1, 3 and 4 only
Answer and explanation in LearnFree account
Question 8 · Medium
A 66-year-old woman with atrial fibrillation has been stable on warfarin with an INR of 2.5. She is given oral fluconazole for vaginal candidiasis. Five days later she has gum bleeding and bruises, and the INR is 6.2. What is the mechanism of this interaction?
1. AInduction of CYP2C9 speeding warfarin clearance
2. BInhibition of CYP2C9 slowing warfarin clearance
3. CReduced vitamin K synthesis by gut flora
4. DDisplacement of warfarin from albumin by fluconazole
Answer and explanation in LearnFree account
Question 9 · Medium
In an isolated tissue experiment, a fixed dose of drug B shifts the log dose-response curve of an agonist parallel to the right, and the same maximum response is reached at higher agonist doses. What type of antagonist is drug B?
1. APartial agonist
2. BPhysiological antagonist
3. CNon-competitive antagonist
4. DCompetitive (surmountable) antagonist
Answer and explanation in LearnFree account
Question 10 · Hard
A 64-year-old man with stage 4 CKD (creatinine clearance 20 mL/min) has MRSA bacteraemia and is to receive IV vancomycin. Compared with a patient with normal kidney function, how should his vancomycin dosing be planned?
1. ASame loading dose, same dosing interval
2. BSmaller loading dose, longer dosing interval
3. CSame loading dose, longer dosing interval
4. DSmaller loading dose, same dosing interval
Answer and explanation in LearnFree account
Question 11 · Easy
A 70-year-old man in the medical ward is started on a fixed daily maintenance dose of a drug with first-order elimination and a half-life of 24 hours, with no loading dose. After about how long will its plasma level reach a practical steady state?
1. A4 to 5 days
2. B10 to 12 days
3. C2 days
4. D24 hours
Answer and explanation in LearnFree account
Question 12 · Easy
A 58-year-old man on simvastatin 40 mg daily for hyperlipidaemia starts drinking two large glasses of grapefruit juice every morning. Three weeks later he has diffuse muscle pain, and serum CK is 9 times the upper limit of normal. Which mechanism raised his statin level?
1. AInhibition of intestinal CYP3A4
2. BInhibition of renal tubular secretion
3. CInduction of hepatic CYP2C9
4. DDisplacement from plasma albumin
Answer and explanation in LearnFree account
Question 13 · Medium
A neonate born at 36 weeks has physiological jaundice. The mother asks why a paediatrician refused to prescribe cotrimoxazole for her baby's suspected infection. Which mechanism makes sulfonamides dangerous in jaundiced newborns?
1. ADisplacement of bilirubin from albumin
2. BHaemolysis in all newborns given sulfonamides
3. CBlocking of bilirubin excretion into bile
4. DInhibition of hepatic glucuronyl transferase
Answer and explanation in LearnFree account
Question 14 · Medium
A 29-year-old man with focal seizures is started on carbamazepine. A level in week 1 is in the therapeutic range and he is seizure-free. In week 5, on the same dose and with good adherence, he has two seizures and the level is below range. What is the most likely explanation?
1. AAutoinduction of its own metabolism
2. BSaturation of its hepatic enzymes
3. CReduced absorption with continued use
4. DTolerance at the sodium channel
Answer and explanation in LearnFree account
Question 15 · Hard
A 61-year-old man with rheumatic AF on warfarin had his dose increased during a six-month rifampicin-based TB course to keep the INR at 2-3. His TB course ended two weeks ago, the warfarin dose was left unchanged, and he now has haematuria and an INR of 7.8. What is the most likely explanation?
1. AWaning of enzyme induction after rifampicin stopped
2. BVitamin K deficiency from TB-related malnutrition
3. CDisplacement of warfarin by isoniazid after stopping
4. DRifampicin-induced liver injury reducing clotting factors
Answer and explanation in LearnFree account
Question 16 · Hard
A 68-year-old man with heart failure and atrial fibrillation on digoxin 0.25 mg daily is started on oral amiodarone. Ten days later he has nausea, vomiting and yellow-tinged vision; serum potassium is 4.3 mmol/L and creatinine unchanged. ECG shows frequent ventricular ectopics. What is the most likely mechanism of this toxicity?
1. AHypokalaemia induced by amiodarone
2. BAmiodarone-induced hypothyroidism
3. CInduction of digoxin metabolism by CYP3A4
4. DReduced P-glycoprotein-mediated digoxin clearance
Answer and explanation in LearnFree account
Question 17 · Easy
A 32-year-old woman with bipolar disorder takes lithium carbonate twice daily, at 8 am and 8 pm. The psychiatry resident wants a serum lithium level for routine monitoring. When should the blood sample be drawn?
1. AJust before the evening dose
2. BAt any time, as the level is constant
3. COne hour after the morning dose
4. DAbout 12 hours after the last dose
Answer and explanation in LearnFree account
Question 18 · Easy
A 26-year-old woman on a combined oral contraceptive pill is started on the NTEP daily regimen for pulmonary tuberculosis. Four months later her urine pregnancy test is positive although she says she missed no pills. Which effect of the anti-TB drugs best explains the pill failure?
1. AReduced gut absorption caused by pyrazinamide
2. BInduction of hepatic CYP3A4 by rifampicin
3. CDisplacement of oestrogen from albumin by ethambutol
4. DInhibition of CYP3A4 by isoniazid
Answer and explanation in LearnFree account
Question 19 · Medium
A 34-year-old man with HIV on tenofovir, lamivudine and dolutegravir is diagnosed with drug-sensitive pulmonary tuberculosis and started on a rifampicin-containing regimen at the ART centre. How should his antiretroviral therapy be adjusted?
1. AReplace rifampicin with streptomycin
2. BGive dolutegravir twice daily during rifampicin
3. CHalve the dose of dolutegravir
4. DStop dolutegravir until TB treatment ends
Answer and explanation in LearnFree account
Question 20 · Medium
A 60-kg man in the ICU needs a gentamicin loading dose to reach a peak plasma level of 8 mg/L. Its volume of distribution in this patient is taken as 0.25 L/kg. What loading dose should be given?
1. A480 mg
2. B120 mg
3. C240 mg
4. D1,920 mg
Answer and explanation in LearnFree account
Question 21 · Medium
A 72-year-old diabetic woman on IV gentamicin for pyelonephritis has a rise in serum creatinine from 1.0 to 1.9 mg/dL over four days. Her trough gentamicin level is above the recommended limit. Apart from reviewing the need for the drug, how should the dosing be changed?
1. AIncrease each dose and keep the interval
2. BChange from IV to intramuscular route
3. CAdd a loading dose and continue as before
4. DLengthen the dosing interval
Answer and explanation in LearnFree account
Question 22 · Medium
A 19-year-old student is admitted to the ICU after an overdose of sustained-release theophylline, with vomiting and sinus tachycardia. Serum theophylline is 40 mg/L at 6 am and 20 mg/L at 2 pm the same day (target range 10-20 mg/L); elimination is first-order. If nothing changes, at about what time will the level reach 10 mg/L?
1. A2 am the next day
2. B6 am the next day
3. C10 pm the same day
4. D6 pm the same day
Answer and explanation in LearnFree account
Question 23 · Medium
A 40-year-old man on lithium for bipolar disorder is admitted with coarse tremor, vomiting, confusion and a serum lithium of 4.2 mEq/L. The nephrologist plans haemodialysis. Which properties of lithium make it easily removed by dialysis? 1. Small volume of distribution 2. Negligible plasma protein binding 3. Low molecular weight and water solubility 4. Extensive hepatic metabolism
1. A2 and 3 only
2. B1, 2 and 4 only
3. C1 only
4. D1, 2 and 3 only
Answer and explanation in LearnFree account

Pharmacokinetics, pharmacodynamics and drug interactions

A 30-year-old woman on the NTEP regimen for pulmonary TB, who was not given pyridoxine, develops burning and tingling in both feet after two months. Her brother, on the same regimen, has no symptoms. Which inherited difference most likely explains why she developed this adverse effect?

Why is probenecid sometimes given together with penicillin?

A 55-year-old man with COPD who smokes 20 cigarettes a day is to be started on oral theophylline. His theophylline clearance is estimated at 4 L/h, oral bioavailability is taken as 100% and the target steady-state level is 10 mg/L. What dose should be given every 12 hours?

A 24-year-old woman with epilepsy on sodium valproate is started on lamotrigine as add-on therapy, titrated as for a patient on no other antiepileptic. Three weeks later she has fever, mucosal erosions and a spreading blistering rash. Why should lamotrigine have been started at a lower dose in her?

A 45-year-old man with ulcerative colitis has been maintained on azathioprine 100 mg/day. At a private clinic he is started on allopurinol 300 mg/day for gout. Four weeks later he has fever and mouth ulcers; TLC is 1,200/µL and platelets 40,000/µL. What explains the marrow suppression?

A 66-year-old woman with atrial fibrillation has been stable on warfarin with an INR of 2.5. She is given oral fluconazole for vaginal candidiasis. Five days later she has gum bleeding and bruises, and the INR is 6.2. What is the mechanism of this interaction?

In an isolated tissue experiment, a fixed dose of drug B shifts the log dose-response curve of an agonist parallel to the right, and the same maximum response is reached at higher agonist doses. What type of antagonist is drug B?

A 64-year-old man with stage 4 CKD (creatinine clearance 20 mL/min) has MRSA bacteraemia and is to receive IV vancomycin. Compared with a patient with normal kidney function, how should his vancomycin dosing be planned?

A 70-year-old man in the medical ward is started on a fixed daily maintenance dose of a drug with first-order elimination and a half-life of 24 hours, with no loading dose. After about how long will its plasma level reach a practical steady state?

A 58-year-old man on simvastatin 40 mg daily for hyperlipidaemia starts drinking two large glasses of grapefruit juice every morning. Three weeks later he has diffuse muscle pain, and serum CK is 9 times the upper limit of normal. Which mechanism raised his statin level?

A neonate born at 36 weeks has physiological jaundice. The mother asks why a paediatrician refused to prescribe cotrimoxazole for her baby's suspected infection. Which mechanism makes sulfonamides dangerous in jaundiced newborns?

A 29-year-old man with focal seizures is started on carbamazepine. A level in week 1 is in the therapeutic range and he is seizure-free. In week 5, on the same dose and with good adherence, he has two seizures and the level is below range. What is the most likely explanation?

A 61-year-old man with rheumatic AF on warfarin had his dose increased during a six-month rifampicin-based TB course to keep the INR at 2-3. His TB course ended two weeks ago, the warfarin dose was left unchanged, and he now has haematuria and an INR of 7.8. What is the most likely explanation?

A 32-year-old woman with bipolar disorder takes lithium carbonate twice daily, at 8 am and 8 pm. The psychiatry resident wants a serum lithium level for routine monitoring. When should the blood sample be drawn?

A 26-year-old woman on a combined oral contraceptive pill is started on the NTEP daily regimen for pulmonary tuberculosis. Four months later her urine pregnancy test is positive although she says she missed no pills. Which effect of the anti-TB drugs best explains the pill failure?

A 34-year-old man with HIV on tenofovir, lamivudine and dolutegravir is diagnosed with drug-sensitive pulmonary tuberculosis and started on a rifampicin-containing regimen at the ART centre. How should his antiretroviral therapy be adjusted?

A 60-kg man in the ICU needs a gentamicin loading dose to reach a peak plasma level of 8 mg/L. Its volume of distribution in this patient is taken as 0.25 L/kg. What loading dose should be given?

A 72-year-old diabetic woman on IV gentamicin for pyelonephritis has a rise in serum creatinine from 1.0 to 1.9 mg/dL over four days. Her trough gentamicin level is above the recommended limit. Apart from reviewing the need for the drug, how should the dosing be changed?