Which opioid analgesic is specifically contraindicated in patients with renal failure, and why?

• A Morphine, because its active metabolite morphine-6-glucuronide accumulates and causes prolonged respiratory depression ✓
• B Fentanyl, because its glucuronide metabolites accumulate and cause CNS toxicity
• C Buprenorphine, because it requires renal clearance of its active form
• D Oxycodone, because renal failure prevents conversion to the active metabolite oxymorphone

Explanation

Morphine is hepatically glucuronidated to morphine-3-glucuronide (M3G, inactive/neuroexcitatory) and morphine-6-glucuronide (M6G, active opioid agonist more potent than morphine). Both M6G and M3G are renally cleared. In renal failure, M6G accumulates to very high levels, causing prolonged and potentially fatal respiratory depression even at standard doses. Fentanyl and buprenorphine are preferred in renal failure because their metabolites are either inactive or not renally excreted. Codeine is also hazardous in renal failure (its active metabolite morphine accumulates), and tramadol increases seizure risk due to accumulation of its O-desmethyl metabolite.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.