Lamotrigine is preferred over carbamazepine for focal epilepsy during pregnancy. The pharmacological basis for lamotrigine's teratogenic risk being lower is:
- A Carbamazepine is a strong inducer of CYP2C9/2C19 that degrades folate; lamotrigine does not induce folate-metabolizing enzymes ✓
- B Lamotrigine does not cross the placenta, while carbamazepine does
- C Carbamazepine shares structural features with imipramine causing cardiac teratogenicity; lamotrigine does not
- D Lamotrigine is rapidly metabolized in fetal liver, preventing fetal exposure
Correct answer: A. Carbamazepine is a strong inducer of CYP2C9/2C19 that degrades folate; lamotrigine does not induce folate-metabolizing enzymes
Explanation
Carbamazepine strongly induces hepatic enzymes including those that increase folate catabolism, contributing to neural tube defects; additionally it has a structural epoxide metabolite (10,11-epoxide) with direct teratogenic potential. Lamotrigine does not induce folate metabolism and has a more favourable teratogenic profile overall, though dose adjustments are needed in pregnancy due to increased glucuronidation. Both drugs cross the placenta.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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