Question

Which of the following drugs, when given with warfarin, induces hepatic CYP450 enzyme?

• A. Ciprofloxacin
• B. Metronidazole
• C. Carbamazepine
• D. Diltiazem

Hint:

CYP450 inducers like carbamazepine, rifampin, and phenytoin reduce warfarin levels. In contrast, inhibitors like ciprofloxacin and metronidazole increase warfarin’s effects.

Answer 1

The Correct Option is C

Cytochrome P450 (CYP450) enzymes are a family of enzymes involved in the metabolism of many drugs. Warfarin, an oral anticoagulant, is metabolized mainly by CYP2C9, CYP1A2, and CYP3A4 isoenzymes in the liver. Some drugs can either inhibit or induce CYP450 enzymes, thereby altering the metabolism of co-administered drugs like warfarin: - Ciprofloxacin and Metronidazole are CYP450 inhibitors. They reduce the metabolism of warfarin, increasing its plasma concentration and thus enhancing its anticoagulant effect, which can lead to bleeding.
- Diltiazem is a calcium channel blocker that also acts as a CYP3A4 inhibitor. It similarly raises warfarin levels by decreasing its metabolism.
- Carbamazepine, an anticonvulsant, is a CYP450 enzyme inducer, especially of CYP3A4. It increases the metabolic rate of warfarin, leading to reduced plasma levels and a decreased anticoagulant effect, which may cause therapeutic failure.
Thus, among the given options, carbamazepine is the correct choice as it induces hepatic CYP450 enzymes, lowering the effectiveness of warfarin.

Answer 2

Warfarin's blood level depends heavily on how fast liver CYP450 enzymes metabolize it, so a drug that speeds up that metabolism will weaken warfarin's effect, while a drug that slows it down will strengthen it. Sorting each option into inducer or inhibitor settles the question.

1. Ciprofloxacin: Ciprofloxacin inhibits CYP450 enzymes, which slows warfarin breakdown and raises its blood level, increasing bleeding risk rather than inducing the enzyme.
2. Metronidazole: Metronidazole is also a CYP450 inhibitor, particularly of CYP2C9, the main isoenzyme handling warfarin. It raises warfarin levels instead of inducing its clearance.
3. Carbamazepine: Carbamazepine is a potent inducer of hepatic CYP450 enzymes, especially CYP3A4. It speeds up warfarin's metabolism, clearing it from the body faster and lowering its blood concentration, which can push a patient's anticoagulation below the therapeutic range.
4. Diltiazem: Diltiazem inhibits CYP3A4, which slows warfarin metabolism and raises its levels, again the opposite of enzyme induction.

Three of the four options here actually slow warfarin's metabolism down; only carbamazepine speeds it up by inducing the enzyme.

So the correct answer is Carbamazepine.