Drug interactions and pharmacogenomics

30 Gulf Prometric Pharmacist (DHA, DOH, MOH, SCFHS, QCHP) practice questions on Drug interactions and pharmacogenomics, part of Pharmacology and Medicinal Chemistry. 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 · Medium

   A patient taking ondansetron and levofloxacin has a QTc of 520 ms and K+ 3.0 mmol/L. What is the best first action?

   1. AStop both drugs and correct K+ and Mg2+
   2. BGive amiodarone to prevent arrhythmia
   3. CAdd a further antiemetic and continue both drugs
   4. DIncrease the levofloxacin dose to cover infection

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   Answer: A · Stop both drugs and correct K+ and Mg2+

   Several QT-prolonging drugs plus hypokalaemia put the patient at high risk of torsades de pointes. The culprit drugs are withdrawn and potassium (above 4 mmol/L) and magnesium are replaced, with an ECG repeated. Other risk factors include female sex, bradycardia and hypomagnesaemia. Amiodarone itself prolongs QT.

   • B: Amiodarone lengthens QT further.
   • C: Another antiemetic may add to the QT risk.
   • D: More levofloxacin would worsen the QT interval.

   Remember this

   For QT prolongation, stop the causative drugs and correct potassium and magnesium.

2. Question 2 · Medium

   A patient who is a CYP2C19 poor metaboliser needs antiplatelet therapy after a stent. What is the issue with clopidogrel, and what is a reasonable alternative?

   1. AFaster clearance of the active drug; use aspirin only
   2. BNo effect of genotype; use clopidogrel
   3. CReduced activation to the active form; use ticagrelor or prasugrel
   4. DExcess active drug and bleeding; use a lower dose

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   Answer: C · Reduced activation to the active form; use ticagrelor or prasugrel

   Clopidogrel is a prodrug that CYP2C19 converts to its active thiol metabolite. Poor metabolisers form less of it and have a higher rate of stent thrombosis and cardiovascular events. Ticagrelor and prasugrel do not depend on CYP2C19 activation, so they are suitable alternatives.

   • A: The problem is lack of activation, not faster clearance.
   • B: Genotype does affect clopidogrel response.
   • D: Poor metabolisers have less, not more, active drug.

   Remember this

   Poor CYP2C19 metabolisers get less active clopidogrel; choose ticagrelor or prasugrel.

3. Question 3 · Easy

   Which gene variant increases the risk of severe cutaneous reactions with allopurinol, particularly in Han Chinese, Thai and Korean patients?

   1. AHLA-B*58:01
   2. BHLA-B*15:02
   3. CTPMT*3A
   4. DCYP2C19*2

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   Answer: A · HLA-B*58:01

   HLA-B*58:01 is strongly associated with allopurinol-induced Stevens-Johnson syndrome, toxic epidermal necrolysis and DRESS. Genotyping before starting is recommended in high-prevalence groups, and an alternative such as febuxostat is chosen if the allele is present. HLA-B*15:02 is linked to carbamazepine.

   • B: HLA-B*15:02 is linked to carbamazepine reactions.
   • C: TPMT*3A causes thiopurine toxicity.
   • D: CYP2C19*2 reduces clopidogrel activation.

   Remember this

   Test HLA-B*58:01 before allopurinol in high-risk ancestry groups.

4. Question 4 · Easy

   A woman taking a combined oral contraceptive begins treatment for tuberculosis and develops breakthrough bleeding. Which drug is most likely responsible?

   1. AStreptomycin
   2. BLevofloxacin
   3. CRifampicin
   4. DIsoniazid

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   Answer: C · Rifampicin

   Rifampicin induces CYP3A4 and other enzymes, which speeds up the metabolism of ethinylestradiol and progestogens and can cause contraceptive failure. Carbamazepine, phenytoin and St John's wort act the same way. A non-hormonal or higher-dose method is advised during and for weeks after the course.

   • A: Streptomycin is not metabolised by liver enzymes and does not induce them.
   • B: Levofloxacin does not induce hepatic enzymes.
   • D: Isoniazid is a weak inhibitor, not an inducer.

   Remember this

   Rifampicin and other inducers reduce hormonal contraceptive efficacy; advise an additional method.

5. Question 5 · Medium

   A patient whose INR was stable at 2.6 on warfarin finishes a week of metronidazole for a dental abscess, and the INR is now 7.1. Which mechanism most likely explains this?

   1. AInduction of CYP2C9 raises warfarin clearance
   2. BIncreased renal excretion of warfarin
   3. CCYP2C9 inhibition reduces S-warfarin clearance
   4. DDisplacement of warfarin from albumin by vitamin K

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   Answer: C · CYP2C9 inhibition reduces S-warfarin clearance

   S-warfarin, the more potent enantiomer, is metabolised mainly by CYP2C9, which metronidazole, azoles and amiodarone inhibit. Plasma levels rise and the INR climbs over several days, so bleeding risk is high. INR is checked early and the warfarin dose is reduced when these drugs are added.

   • A: Induction would lower the INR.
   • B: Metronidazole does not increase renal excretion of warfarin.
   • D: Vitamin K does not displace warfarin from albumin.

   Remember this

   Azoles, metronidazole and amiodarone raise INR by inhibiting CYP2C9; monitor closely.

6. Question 6 · Medium

   A man on simvastatin 40 mg is prescribed clarithromycin for pneumonia and later has muscle pain and dark urine. Which mechanism most likely explains this?

   1. ACYP3A4 induction lowers simvastatin levels
   2. BClarithromycin increases renal tubular secretion of simvastatin
   3. CCYP3A4 inhibition raising simvastatin levels
   4. DClarithromycin displaces simvastatin from albumin

   Answer and explanation in LearnFree account

7. Question 7 · Medium

   A man taking sertraline is started on linezolid for a resistant infection. Two days later he has agitation, sweating, tremor, diarrhoea and inducible clonus. What is the diagnosis?

   1. AAlcohol withdrawal with delirium
   2. BMalignant hyperthermia after anaesthesia
   3. CNeuroleptic malignant syndrome with rigidity
   4. DSerotonin syndrome from the combination

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8. Question 8 · Hard

   A woman with normal CYP2D6 genotype takes codeine for pain, together with paroxetine, and gets almost no analgesia. Which explanation is correct?

   1. ACodeine is active as such and the interaction is unrelated
   2. BParoxetine inhibits CYP2D6, so morphine is barely formed
   3. CParoxetine induces CYP3A4, so codeine is cleared quickly
   4. DParoxetine blocks mu receptors

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9. Question 9 · Medium

   A patient found to have two non-functional TPMT alleles is to start azathioprine. What is the recommended approach?

   1. AAvoid it or cut the dose sharply
   2. BUse it only with allopurinol at the full usual dose
   3. CContinue at the usual dose and check bilirubin
   4. DUse a double dose to compensate for slow clearance

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10. Question 10 · Hard

    A patient on warfarin received rifampicin for 6 weeks, and the warfarin dose was doubled to keep the INR in range. Rifampicin is now stopped. What should be expected, and what is the best plan?

    1. AINR will rise over weeks; cut warfarin and monitor INR often
    2. BINR changes immediately, so stop warfarin for a month
    3. CINR will fall further, so increase the dose again
    4. DINR stays stable, so no change in dose is needed at all

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11. Question 11 · Medium

    A patient starting warfarin is found to carry CYP2C9*3/*3 and VKORC1 -1639 A/A. What does this genotype predict?

    1. AA much higher dose is needed because of warfarin resistance
    2. BWarfarin is ineffective and cannot be used at all
    3. CA much lower dose is needed and early bleeding risk is high
    4. DThe usual dose is needed, as genotype does not affect warfarin

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12. Question 12 · Easy

    A breastfeeding mother who is a CYP2D6 ultrarapid metaboliser is prescribed codeine after a caesarean section. What is the main risk?

    1. APoor pain relief from too little morphine
    2. BMorphine toxicity in her and her infant
    3. CSevere liver injury from a toxic metabolite
    4. DBone marrow suppression in the infant

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13. Question 13 · Medium

    A man with COPD stable on theophylline is given ciprofloxacin. Three days later he has nausea, tremor, tachycardia and a seizure. What mechanism best explains this?

    1. AInduction of CYP3A4, which forms a toxic metabolite
    2. BInhibition of CYP1A2, which lowers theophylline clearance
    3. CDisplacement of theophylline from plasma albumin
    4. DCompetition for renal tubular secretion

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14. Question 14 · Medium

    A man in Dubai on long-term amiodarone is about to start sofosbuvir-based treatment for hepatitis C. What is the main interaction risk?

    1. ASevere hyperkalaemia
    2. BPulmonary fibrosis within the first week
    3. CHepatitis C relapse from low sofosbuvir levels
    4. DSevere symptomatic bradycardia

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15. Question 15 · Medium

    A man with HIV has dizziness, vivid dreams and poor concentration 6 weeks after starting efavirenz 600 mg daily, and his plasma efavirenz level is high. Genotyping shows CYP2B6*6/*6. Which statement is correct?

    1. AFast CYP2B6 metabolism lowers efavirenz levels; the dose should be raised to 800 mg daily
    2. BThe variant predicts an immune skin reaction; efavirenz must be stopped and never restarted
    3. CSlow CYP2B6 metabolism raises efavirenz levels; a lower dose of 400 or 200 mg can be considered
    4. DEfavirenz is cleared only by CYP3A4, so the genotype is unrelated to his symptoms

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16. Question 16 · Easy

    Contraceptive failure is a recognised consequence of enzyme induction by which of the following drugs?

    1. ARifampicin
    2. BErythromycin
    3. CCimetidine
    4. DFluconazole

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17. Question 17 · Medium

    A patient taking clopidogrel after a myocardial infarction needs acid suppression to prevent bleeding. Which of these should be avoided because it inhibits CYP2C19?

    1. AOmeprazole
    2. BSucralfate
    3. CPantoprazole
    4. DFamotidine

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18. Question 18 · Medium

    A woman in Muscat takes carbamazepine for epilepsy and asks about contraception. Which method is not affected by enzyme induction?

    1. ACombined oral contraceptive
    2. BCopper intrauterine device
    3. CProgestogen-only pill
    4. DEtonogestrel implant

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19. Question 19 · Medium

    A kidney transplant recipient stable on tacrolimus begins taking St John's wort for low mood, and the tacrolimus trough falls from 8 to 3 ng/mL. What is the best action?

    1. ASwitch the tacrolimus to a drug that inhibits CYP3A4
    2. BSeparate the two doses by 12 hours so they do not meet
    3. CStop St John's wort and monitor the tacrolimus level closely
    4. DDouble the tacrolimus dose and continue St John's wort

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20. Question 20 · Medium

    A Thai expatriate with gout and stage 3 chronic kidney disease is about to start allopurinol. What is the most appropriate step before treatment?

    1. AStart 300 mg daily to control uric acid quickly
    2. BGive a corticosteroid with the first doses to prevent rash
    3. CTest for TPMT before the first dose
    4. DTest for HLA-B*5801 and start at a low dose with slow titration

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21. Question 21 · Medium

    A man taking colchicine 500 micrograms twice daily for gout prophylaxis needs a 7-day course of clarithromycin. What should the pharmacist advise?

    1. AContinue both, as macrolides do not affect colchicine
    2. BDouble the colchicine dose to prevent a flare
    3. CGive colchicine 2 hours before the antibiotic
    4. DWithhold colchicine, or use a non-interacting antibiotic

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22. Question 22 · Hard

    A patient well controlled on fluoxetine is switched to tranylcypromine for resistant depression. Fluoxetine is stopped today. What is the minimum washout before the MAO inhibitor is started?

    1. A5 weeks, because norfluoxetine persists for weeks
    2. B2 weeks, as with other SSRIs
    3. C48 hours, because fluoxetine is cleared quickly
    4. D1 week, as with short-acting antidepressants

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23. Question 23 · Easy

    Clopidogrel is a prodrug that depends mainly on which enzyme for conversion to its active metabolite?

    1. ACYP2E1
    2. BCYP1A2
    3. CCYP2D6
    4. DCYP2C19

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24. Question 24 · Medium

    A man with schizophrenia on haloperidol is found to have a QTc of 505 ms. His serum potassium is 3.1 mmol/L. What is the best first step?

    1. AAdd a second antipsychotic so the haloperidol dose can fall
    2. BContinue haloperidol unchanged and repeat the ECG in 3 months
    3. CReplace potassium and magnesium, then review the QT-prolonging drugs
    4. DAdd amiodarone to protect against ventricular arrhythmia

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25. Question 25 · Easy

    A man of Han Chinese ancestry is about to start carbamazepine for epilepsy. Which genetic test is recommended first?

    1. AHLA-B*58:01 genotyping
    2. BHLA-B*15:02 genotyping
    3. CTPMT activity testing
    4. DCYP2C19 genotyping

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