Clinical pharmacology: TDM, special populations and drug safety

33 NEET-PG practice questions on Clinical pharmacology: TDM, special populations and drug safety, part of Pharmacology. The first 25 are below; the first 5 with answers and explanations (tap Show answer after you have chosen), the rest in Learn with a free account.

1. Question 1 · Hard

   On maintenance haemodialysis three times a week, a man with metastatic prostate cancer was started on oral morphine 10 mg four-hourly for bone pain. After five days he is drowsy, his respiratory rate is 10/min and he has myoclonic jerks, although his pain is controlled. Naloxone has been given and he is more alert. He weighs 58 kg, has no liver disease, and is passing almost no urine. His family wants him to stay at home with good pain control and as few injections as possible. Which opioid is the best replacement for long-term pain control?

   1. AIntramuscular pethidine
   2. BOral tramadol
   3. CTransdermal fentanyl
   4. DOral codeine

   Show answerHide answer

   Answer: C · Transdermal fentanyl

   Morphine is glucuronidated to morphine-3-glucuronide and morphine-6-glucuronide, which are excreted by the kidneys; in renal failure they accumulate, causing sedation, respiratory depression and neuroexcitation such as myoclonus. Fentanyl is metabolised by CYP3A4 to inactive products and is preferred in advanced CKD and dialysis, with careful titration. Codeine (via morphine), tramadol and pethidine (via norpethidine) all have metabolites that accumulate.

   • A: Pethidine's metabolite norpethidine accumulates and causes seizures.
   • B: Tramadol and its active metabolite accumulate and lower the seizure threshold.
   • D: Codeine is converted to morphine, so its metabolites accumulate in the same way.

   Remember this

   In dialysis patients, avoid morphine, codeine, tramadol and pethidine; fentanyl has no active renally cleared metabolites.

2. Question 2 · Medium

   Eight months after a live-donor renal transplant, a man stable on tacrolimus, mycophenolate and prednisolone is given clarithromycin by a local clinic for a chest infection. Five days later he has a fine tremor, BP 162/96 mmHg and serum creatinine 2.1 mg/dL (baseline 1.2). The tacrolimus trough is 19 ng/mL (target 5-8). By what mechanism did this happen?

   1. AReduced renal excretion of tacrolimus
   2. BInduction of CYP3A4 in the liver
   3. CInhibition of CYP3A4 and P-glycoprotein
   4. DDisplacement of tacrolimus from albumin

   Show answerHide answer

   Answer: C · Inhibition of CYP3A4 and P-glycoprotein

   Clarithromycin strongly inhibits CYP3A4 and P-glycoprotein, the main routes of tacrolimus clearance in the gut wall and liver, so trough levels can double or triple within days. The result is calcineurin-inhibitor nephrotoxicity, hypertension and neurotoxicity such as tremor. Azithromycin is the safer macrolide; if an interacting drug is essential, the tacrolimus dose is cut and troughs are rechecked.

   • A: Tacrolimus is cleared by the liver, not the kidney.
   • B: Induction (as by rifampicin) lowers tacrolimus levels and risks rejection.
   • D: Tacrolimus is mainly bound to red cells; displacement does not raise the whole-blood trough.

   Remember this

   Clarithromycin, azoles and diltiazem raise tacrolimus and ciclosporin levels by CYP3A4 inhibition.

3. Question 3 · Hard

   The ward pharmacist in a district hospital asks the intern to estimate kidney function before dosing a renally cleared antibiotic for a retired schoolteacher with pneumonia. She is 70 years old, weighs 60 kg and has a serum creatinine of 1.4 mg/dL, which the intern calls only slightly high. Using the Cockcroft-Gault equation, what is her approximate creatinine clearance?

   1. AAbout 29 mL/min
   2. BAbout 42 mL/min
   3. CAbout 50 mL/min
   4. DAbout 35 mL/min

   Show answerHide answer

   Answer: D · About 35 mL/min

   Cockcroft-Gault: CrCl = (140 - age) x weight in kg / (72 x serum creatinine), multiplied by 0.85 for women. Here (140 - 70) x 60 = 4,200, and 72 x 1.4 = 100.8, giving about 41.7 mL/min, which times 0.85 gives about 35 mL/min. Forgetting the female correction gives the tempting 42 mL/min. A normal-looking creatinine can hide a markedly reduced clearance in a small, elderly woman.

   • A: 29 mL/min underestimates it, as if the female factor were applied twice.
   • B: 42 mL/min omits the 0.85 correction for women.
   • C: 50 mL/min overestimates her clearance; it does not follow from the equation.

   Remember this

   Cockcroft-Gault = (140 - age) x weight / (72 x creatinine), x 0.85 in women.

4. Question 4 · Medium

   On day 4 of once-daily amikacin for a Gram-negative pneumonia in the medical ICU, a farmer's serum creatinine has risen from 0.9 to 1.5 mg/dL and he complains of mild tinnitus. Urine output is 1.2 L/day. The intensivist wants the drug level that best shows accumulation and the risk of further kidney and ear damage. Which sample is most useful?

   1. ALevel in the bronchial aspirate
   2. BTrough level just before the next dose
   3. CPeak level 30 minutes after the dose
   4. D24-hour urinary amikacin excretion

   Show answerHide answer

   Answer: B · Trough level just before the next dose

   Aminoglycoside efficacy depends on the peak (concentration-dependent killing), but toxicity to the renal tubule and inner ear relates to sustained exposure, reflected by the trough. With extended-interval dosing the trough should be very low; a raised trough means accumulation and calls for a longer interval or another drug. Rising creatinine with tinnitus needs this check at once.

   • A: Lung tissue levels are not used to monitor safety.
   • C: The peak guides efficacy against the organism, not toxicity.
   • D: Urinary drug excretion is not used to monitor aminoglycoside safety.

   Remember this

   Aminoglycosides: peak for efficacy, trough for toxicity; a high trough means accumulation.

5. Question 5 · Medium

   Profound bradycardia and hypotension follow the usual starting oral dose of propranolol in a man with alcohol-related cirrhosis and a large portosystemic shunt on Doppler, whereas his brother, with normal liver function, tolerates the same dose well. Propranolol is cleared almost entirely by the liver and has a high hepatic extraction ratio. Which change best explains the exaggerated response?

   1. AUp-regulation of beta-1 receptors
   2. BLess first-pass hepatic extraction
   3. CReduced renal excretion of the drug
   4. DFaster absorption from the gut

   Show answerHide answer

   Answer: B · Less first-pass hepatic extraction

   Drugs with a high hepatic extraction ratio, such as propranolol, morphine, lidocaine, verapamil and nitrates, are largely removed on their first pass through the liver, so their oral bioavailability is low. In cirrhosis, portosystemic shunts let the oral dose bypass the liver and fewer working hepatocytes extract less, so bioavailability and peak levels rise several-fold. Oral doses of these drugs are started low in cirrhosis; intravenous doses are affected much less.

   • A: Receptor up-regulation follows long-term beta-blockade and causes rebound on stopping, not an exaggerated first-dose response.
   • C: Propranolol is cleared by the liver; renal excretion of the unchanged drug is negligible.
   • D: The rate of gut absorption is not the issue; the amount that escapes the liver is.

   Remember this

   In cirrhosis, oral high-extraction drugs (propranolol, morphine, verapamil) escape first-pass metabolism, so start low.

6. Question 6 · Medium

   Over eight months, ADR monitoring centres in four states send 23 reports of Stevens-Johnson syndrome in patients taking a recently marketed antiepileptic, a reaction not mentioned in its prescribing information. The National Coordination Centre flags the association for further evaluation. In pharmacovigilance terms, this flagged association is a:

   1. ASignal
   2. BMedication error
   3. CSerious adverse event
   4. DSide effect

   Answer and explanation in LearnFree account

7. Question 7 · Medium

   A sponsor plans a phase III trial in India of a new oral anticoagulant molecule not yet approved anywhere. It will enrol 1,200 patients with atrial fibrillation at 30 hospitals across six states. Under the New Drugs and Clinical Trials Rules 2019, what must be in place before the first participant is enrolled?

   1. AState drug controller licence alone
   2. BEthics committee approval alone
   3. CCDSCO permission and ethics committee approval
   4. DICMR approval and CDSCO permission

   Answer and explanation in LearnFree account

8. Question 8 · Medium

   A metal-on-metal hip prosthesis fitted at a district hospital fails within two years, with a soft-tissue mass and raised serum cobalt. Revision surgery shows extensive metallosis, and two similar failures of the same model have occurred in the unit this year. The orthopaedic surgeon wants to report the event to the national system. Under which programme should it be reported?

   1. ANational AEFI surveillance
   2. BMateriovigilance Programme of India
   3. CPharmacovigilance Programme of India
   4. DHaemovigilance Programme of India

   Answer and explanation in LearnFree account

9. Question 9 · Easy

   Pharmacovigilance cell of a medical college: the PvPI technical associate has to grade how likely it is that a cotrimoxazole course caused a maculopapular rash in a ward patient. The rash began on day 6, faded after the drug was stopped, and the patient had also taken paracetamol. Which tool does the programme use for this causality assessment?

   1. AHartwig and Siegel severity scale
   2. BSchumock and Thornton criteria
   3. CCommon Terminology Criteria (CTCAE)
   4. DWHO-UMC causality scale

   Answer and explanation in LearnFree account

10. Question 10 · Hard

    An elderly widow with atrial fibrillation and CKD stage 3, on digoxin, was recently given verapamil for rate control. She now has vomiting, confusion and green-yellow vision. Pulse is 38/min with high-grade AV block, BP 84/50 mmHg, serum potassium 6.4 mmol/L and digoxin level 4.8 ng/mL. She is cold, clammy and drowsy. Her daughter says she has taken the tablets as prescribed and there was no overdose; serum creatinine is 2.2 mg/dL, up from 1.6 last month. Atropine has not raised her heart rate. What is the treatment of choice now?

    1. AHaemodialysis
    2. BIV calcium gluconate
    3. CDigoxin-specific antibody fragments
    4. DIV insulin with dextrose alone

    Answer and explanation in LearnFree account

11. Question 11 · Medium

    Consider these statements on pharmacokinetics in the elderly: 1. Renal clearance falls with age even when serum creatinine is normal. 2. The volume of distribution of lipid-soluble drugs is reduced. 3. Lower serum albumin can raise the free fraction of acidic drugs such as phenytoin. 4. First-pass hepatic metabolism is increased. Which statements are correct?

    1. A1, 3 and 4 only
    2. B2 and 4 only
    3. C1, 2 and 3 only
    4. D1 and 3 only

    Answer and explanation in LearnFree account

12. Question 12 · Hard

    Spontaneous reports in a national ADR database: for drug X, 20 of its 400 reports describe Stevens-Johnson syndrome; for all other drugs, 100 of 40,000 reports describe it. What is the proportional reporting ratio (PRR) for drug X and SJS?

    1. A200
    2. B0.05
    3. C20
    4. D2

    Answer and explanation in LearnFree account

13. Question 13 · Medium

    Three weeks after starting carbamazepine for focal epilepsy, a college student who had been seizure-free on 400 mg/day has two breakthrough focal seizures. She has taken every dose. Her carbamazepine level was 8 mg/L on day 5 and is now 3.5 mg/L (target 4-12 mg/L). No other drug has been added. Which explains the fall in level?

    1. ASaturation of hepatic enzymes
    2. BReduced oral absorption with time
    3. CInduction of its own metabolism by CYP3A4
    4. DDisplacement from plasma albumin

    Answer and explanation in LearnFree account

14. Question 14 · Medium

    At the cardiology clinic, a retired weaver with heart failure and atrial fibrillation on digoxin 0.25 mg each morning feels well: no nausea, no visual change, pulse 76/min and irregular. Serum potassium is 4.3 mmol/L and creatinine 1.0 mg/dL. A digoxin level of 3.0 ng/mL (target 0.5-0.9) is reported on a sample taken 90 minutes after his morning tablet. He also takes furosemide 40 mg, ramipril 5 mg and apixaban, and his previous level six months ago, drawn in the evening, was 0.8 ng/mL on the same dose. What should be done next?

    1. AHalve the dose and recheck in a week
    2. BGive digoxin-specific antibody fragments
    3. CRepeat the level at least 6 hours after a dose
    4. DStop digoxin and start amiodarone

    Answer and explanation in LearnFree account

15. Question 15 · Easy

    A schoolteacher on lithium carbonate 900 mg/day for bipolar I disorder comes to the psychiatry OPD for his routine three-monthly check. He takes the drug twice daily, the last dose at 9 p.m. He has no tremor or diarrhoea, and his TSH and creatinine were normal last month. When should blood be drawn for the serum lithium level?

    1. AAbout 12 hours after the last dose
    2. BOne to two hours after the last dose
    3. CWithin 30 minutes of the morning dose
    4. DAt any time, since levels are steady

    Answer and explanation in LearnFree account

16. Question 16 · Medium

    Cirrhosis with tense ascites and oesophageal varices has been diagnosed in a retired driver, who now complains of pain from osteoarthritis of both knees. Serum creatinine is 1.1 mg/dL. He asks which painkiller he may use regularly. He drinks no alcohol now and has had no bleeding for two years. What is the best choice?

    1. ADiclofenac gel with oral naproxen
    2. BTramadol 100 mg four times a day
    3. CParacetamol, up to about 2 g a day
    4. DIbuprofen 400 mg three times a day

    Answer and explanation in LearnFree account

17. Question 17 · Medium

    Which trial phase gives a human subject a sub-therapeutic microdose of a new molecule only to study its pharmacokinetics?

    1. APhase 0
    2. BPhase II
    3. CPhase IV
    4. DPhase I

    Answer and explanation in LearnFree account

18. Question 18 · Easy

    Five years after a new gliptin was launched in India, spontaneous reports and a cohort study of 40,000 users reveal a small excess of acute pancreatitis that the pre-marketing trials had missed. Most of the cases occurred after more than a year of use. This stage of drug evaluation is called:

    1. APhase IV
    2. BPhase II
    3. CPhase I
    4. DPhase III

    Answer and explanation in LearnFree account

19. Question 19 · Medium

    A heavy beedi smoker with COPD has been stable for a year on sustained-release theophylline 300 mg twice daily, with a level of 12 mg/L. He stops smoking completely after an admission. Six weeks later he presents with palpitations, vomiting and tremor; the level is 26 mg/L (target 10-20). What explains the rise?

    1. AReduced renal excretion of theophylline
    2. BSaturation of glucuronidation in the liver
    3. CLoss of CYP1A2 induction after quitting
    4. DIncreased absorption from the gut

    Answer and explanation in LearnFree account

20. Question 20 · Medium

    eGFR 24 mL/min/1.73 m2 is reported at the annual check-up of a shopkeeper with type 2 diabetes for 15 years who takes metformin 1 g twice daily, glimepiride and telmisartan. His eGFR was 38 a year ago. HbA1c is 7.4%. He has no symptoms and his potassium is 5.0 mmol/L. What should be done about the metformin?

    1. AStop it because of lactic acidosis risk
    2. BContinue at the same dose
    3. CHalve the dose and recheck eGFR in a year
    4. DChange to the extended-release form

    Answer and explanation in LearnFree account

21. Question 21 · Medium

    A Hyderabad company wants to market a generic version of an approved metformin extended-release tablet. Instead of fresh efficacy trials, the regulator asks for a study comparing its AUC and Cmax with the innovator product in healthy volunteers. For approval, the 90% confidence interval of the ratio of these values must lie within:

    1. A90-110%
    2. B80-125%
    3. C70-143%
    4. D95-105%

    Answer and explanation in LearnFree account

22. Question 22 · Hard

    In the surgical ICU, a man with MRSA bacteraemia from an infected central line is on IV vancomycin; creatinine is 1.1 mg/dL. He has been afebrile for 24 hours, repeat blood cultures are sterile, urine output is good, and the isolate's vancomycin MIC is 1 mg/L. The unit protocol still aims for a trough of 15-20 mg/L, and his trough is 11 mg/L, so the resident proposes increasing the dose. The clinical pharmacist points to the 2020 consensus guideline on vancomycin monitoring. According to that guideline, what should guide the dose?

    1. ATrough of 5-10 mg/L in every patient
    2. BTrough of 15-20 mg/L in every patient
    3. CPeak level above 40 mg/L
    4. DAUC/MIC ratio of 400-600, estimated from levels

    Answer and explanation in LearnFree account

23. Question 23 · Easy

    A pharmacist in Kozhikode dispenses cefpodoxime tablets against a prescription and enters the prescriber's name, the patient's name and the quantity in a separate register that must be kept for three years. Under which schedule of the Drugs Rules is this drug listed?

    1. ASchedule M
    2. BSchedule G
    3. CSchedule H1
    4. DSchedule X

    Answer and explanation in LearnFree account

24. Question 24 · Hard

    Serum albumin 2.0 g/dL (normal 3.5-5.0) and total phenytoin 8 mg/L (therapeutic 10-20) are reported for a woman with alcoholic cirrhosis on phenytoin 300 mg/day after a head injury. Renal function is normal, she has had no seizures, and there is no nystagmus or ataxia. Her bilirubin is 2.4 mg/dL, and the resident on duty wants to raise the dose to 400 mg/day to bring the total level into the therapeutic range. Using the Sheiner-Tozer correction (corrected = measured / [0.2 x albumin + 0.1]), what is the correct interpretation?

    1. AAbout 8 mg/L, subtherapeutic; increase
    2. BAbout 4 mg/L, subtherapeutic; add a drug
    3. CAbout 16 mg/L, in range; do not increase
    4. DAbout 32 mg/L, toxic; withhold doses

    Answer and explanation in LearnFree account

25. Question 25 · Easy

    What is the term for the return of an adverse reaction when the suspected drug is deliberately restarted after it had been stopped?

    1. APositive rechallenge
    2. BPositive dechallenge
    3. CIdiosyncrasy
    4. DTachyphylaxis

    Answer and explanation in LearnFree account