Saudi Prometric Pharmacist Drug Interactions and Adverse Effects 1 — Questions and Answers
Question 1: A patient on warfarin starts taking fluconazole for a vaginal yeast infection. What is the expected pharmacokinetic interaction?
- Fluconazole inhibits CYP2C9, increasing warfarin levels and INR — increased bleeding risk (Correct answer)
- Fluconazole induces CYP2C9, decreasing warfarin levels
- No interaction — fluconazole only affects CYP3A4
- Fluconazole enhances warfarin absorption from the GI tract
Correct answer: Fluconazole inhibits CYP2C9, increasing warfarin levels and INR — increased bleeding risk
Fluconazole is a potent CYP2C9 inhibitor. Since warfarin (S-enantiomer) is primarily metabolized by CYP2C9, fluconazole inhibition dramatically raises warfarin plasma levels, increasing INR and bleeding risk. Even a short course (3–7 days) can cause significant INR elevation.
Question 2: Which adverse effect is associated with ACE inhibitor therapy and is caused by bradykinin accumulation?
- Dry, persistent cough — occurs in 10–15% of patients (Correct answer)
- Hyperkalemia — due to aldosterone reduction
- Renal insufficiency — in bilateral renal artery stenosis
- Angioedema — life-threatening, rare (0.1–0.5%)
Correct answer: Dry, persistent cough — occurs in 10–15% of patients
ACE inhibitors prevent bradykinin degradation (ACE normally breaks down bradykinin). Bradykinin accumulation in the airways causes a characteristic dry, non-productive cough in 10–15% of patients. Switching to an ARB (which does not affect bradykinin) resolves the cough. Angioedema is rarer but life-threatening.
Question 3: A patient taking MAO inhibitors (phenelzine) eats tyramine-rich food. What reaction occurs?
- Hypertensive crisis — tyramine cannot be metabolized, causes massive norepinephrine release (Correct answer)
- Hypotension and bradycardia
- Serotonin syndrome
- Peripheral neuropathy
Correct answer: Hypertensive crisis — tyramine cannot be metabolized, causes massive norepinephrine release
MAO in the gut wall normally inactivates tyramine (an indirect sympathomimetic in aged foods). MAO inhibitors block this, allowing tyramine to enter systemic circulation, displace norepinephrine from sympathetic nerve terminals, and cause severe, potentially fatal hypertensive crisis ('cheese reaction').
Question 4: Which class of drugs can cause hyperkalemia when combined with ACE inhibitors or ARBs?
- Potassium-sparing diuretics and aldosterone antagonists (spironolactone, eplerenone) (Correct answer)
- Thiazide diuretics
- Loop diuretics
- Beta-blockers
Correct answer: Potassium-sparing diuretics and aldosterone antagonists (spironolactone, eplerenone)
ACE inhibitors/ARBs reduce aldosterone, causing potassium retention. Adding potassium-sparing diuretics (amiloride, triamterene) or MRAs (spironolactone) further reduces renal potassium excretion, causing potentially dangerous hyperkalemia (>6.0 mEq/L with cardiac arrest risk).
Question 5: A patient taking lithium is prescribed ibuprofen for joint pain. What should the pharmacist advise?
- Avoid NSAIDs — they increase lithium levels via renal prostaglandin inhibition; use paracetamol instead (Correct answer)
- NSAIDs are safe with lithium — no significant interaction
- Use low-dose ibuprofen only — safe at <400 mg/day
- Increase fluid intake when taking ibuprofen with lithium
Correct answer: Avoid NSAIDs — they increase lithium levels via renal prostaglandin inhibition; use paracetamol instead
NSAIDs inhibit renal prostaglandin synthesis, causing reduced renal blood flow and sodium retention. The kidney compensates by reabsorbing sodium (and lithium, as they compete in the same transporter), raising lithium levels by 15–60%, potentially causing toxicity. Paracetamol is the safe analgesic alternative.
Question 6: A patient on methotrexate is prescribed trimethoprim for a urinary tract infection. What is the major concern?
- Additive folate antagonism causing severe myelosuppression and mucositis (Correct answer)
- Methotrexate reduces trimethoprim renal excretion
- Trimethoprim induces methotrexate metabolism, reducing efficacy
- No significant interaction — different mechanisms
Correct answer: Additive folate antagonism causing severe myelosuppression and mucositis
Both methotrexate and trimethoprim inhibit dihydrofolate reductase (DHFR), with additive folate antagonism. Combined, they cause potentially fatal bone marrow suppression (pancytopenia), severe mucositis, and GI toxicity. Trimethoprim should be avoided in patients on MTX; nitrofurantoin is a safer UTI alternative.
Saudi Prometric Pharmacist Drug Interactions and Adverse Effects 1
A patient on warfarin starts taking fluconazole for a vaginal yeast infection.
What is the expected pharmacokinetic interaction?