Question - Loperamide is a phenylpiperidine opioid that slows GI transit by stimulating mu receptors, among other effects. This drug has become popular via its misuse and has been labeled as a “poor man’s methadone”. How do abusers of loperamide enhance the absorption and CNS penetrance of this drug?
Answer - Abusers of loperamide have been known to inhibit the enzyme involved in loperamide metabolism (CYP3A4) by the co-ingestion of grapefruit juice or cimetidine. These abusers also may use black pepper as an inhibitor of both P-gp and CYP3A4. (Wu P and Juurlink DN. Clinical review: Loperamide toxicity. 2017 Anns Emerg Med 70(1):245-252)