MTM Pharmacotherapy Review & Drug Interactions 4 — Questions and Answers
Question 1: Which drug is a substrate of CYP2D6 and may accumulate to toxic levels in 'poor metabolizers' of this enzyme?
- Warfarin
- Codeine (Correct answer)
- Metformin
- Lisinopril
Correct answer: Codeine
Codeine is converted to its active analgesic form (morphine) by CYP2D6; poor metabolizers accumulate codeine with little analgesia, while ultra-rapid metabolizers risk morphine toxicity.
Question 2: A patient taking simvastatin 80 mg is prescribed amlodipine. What adjustment is recommended?
- No adjustment needed; amlodipine does not affect statins
- Reduce simvastatin to no more than 20 mg/day due to CYP3A4 inhibition (Correct answer)
- Discontinue amlodipine and switch to a non-calcium channel blocker
- Switch to rosuvastatin, which is not metabolized by CYP3A4
Correct answer: Reduce simvastatin to no more than 20 mg/day due to CYP3A4 inhibition
Amlodipine is a weak CYP3A4 inhibitor; simvastatin 80 mg is already restricted due to myopathy risk, and the FDA recommends limiting simvastatin to 20 mg/day when co-administered with amlodipine.
Question 3: What is the mechanism of action of direct oral anticoagulants (DOACs) such as rivaroxaban?
- Inhibit vitamin K epoxide reductase, blocking clotting factor synthesis
- Directly inhibit activated Factor Xa, preventing thrombin generation (Correct answer)
- Activate antithrombin III to inhibit thrombin and Factor Xa
- Inhibit thrombin directly and irreversibly
Correct answer: Directly inhibit activated Factor Xa, preventing thrombin generation
Rivaroxaban is a direct Factor Xa inhibitor that blocks the conversion of prothrombin to thrombin without requiring antithrombin as a cofactor.
Question 4: Which medication requires therapeutic drug monitoring due to its narrow therapeutic index and non-linear (Michaelis-Menten) pharmacokinetics?
- Amoxicillin
- Phenytoin (Correct answer)
- Metoprolol
- Omeprazole
Correct answer: Phenytoin
Phenytoin exhibits saturable (zero-order at therapeutic concentrations) Michaelis-Menten kinetics, causing small dose increases to produce disproportionately large plasma level elevations.
Question 5: A diabetic patient on glipizide starts a fluoroquinolone antibiotic. What glucose-related adverse effect is possible?
- Persistent hyperglycemia due to insulin resistance
- Both hypoglycemia and hyperglycemia, depending on the specific fluoroquinolone (Correct answer)
- No significant interaction; fluoroquinolones are safe with sulfonylureas
- Hyperglycemia only, due to hepatic glucose release
Correct answer: Both hypoglycemia and hyperglycemia, depending on the specific fluoroquinolone
Fluoroquinolones can cause both hypoglycemia (by stimulating insulin secretion, especially gatifloxacin/moxifloxacin) and hyperglycemia by interfering with pancreatic beta-cell function.
Question 6: Angiotensin-converting enzyme (ACE) inhibitors are contraindicated in pregnancy primarily because they cause:
- Maternal hypertension and stroke
- Fetal renal tubular dysgenesis and oligohydramnios (Correct answer)
- Neonatal hyperthyroidism
- Teratogenic limb defects in the first trimester only
Correct answer: Fetal renal tubular dysgenesis and oligohydramnios
ACE inhibitors impair fetal renal development in the second and third trimesters, leading to fetal renal tubular dysgenesis, oligohydramnios, and potentially fetal death.
Question 7: Which drug interaction results from cholestyramine's mechanism of action as a bile acid sequestrant?
- Inhibition of hepatic CYP3A4, elevating co-administered drug levels
- Decreased GI absorption of many drugs taken concomitantly (Correct answer)
- Induction of P-glycoprotein, reducing drug bioavailability selectively
- Competition for renal tubular secretion of co-administered drugs
Correct answer: Decreased GI absorption of many drugs taken concomitantly
Cholestyramine binds drugs in the GI tract, reducing their absorption; this applies to thyroid hormones, warfarin, digoxin, and many other drugs, requiring 1-4 hours of separation.
MTM Pharmacotherapy Review & Drug Interactions 4
Which drug is a substrate of CYP2D6 and may accumulate to toxic levels in 'poor metabolizers' of this enzyme?