In renal failure, which morphine metabolite can accumulate and cause narcosis and ventilatory depression?

In renal failure, which morphine metabolite can accumulate and cause narcosis and ventilatory depression?

• A. Active metabolite morphine-6-glucuronide accumulates
• B. Inactive morphine-3-glucuronide accumulates
• C. Unchanged morphine accumulates
• D. No accumulation occurs

Answer: (A)

In renal failure, the kidneys can’t clear morphine metabolites efficiently, so the active metabolite morphine-6-glucuronide accumulates. This metabolite is pharmacologically potent at mu-opioid receptors and can cross into the central nervous system, where its buildup enhances sedation and depresses respiration. Morphine-3-glucuronide, while it may also accumulate, is not analgesic and does not drive narcosis or ventilatory depression. Unchanged morphine and no accumulation are less relevant in this context, as the key toxicity in renal impairment comes from the active metabolite that remains in circulation longer due to reduced renal clearance.

In renal failure, the kidneys can’t clear morphine metabolites efficiently, so the active metabolite morphine-6-glucuronide accumulates. This metabolite is pharmacologically potent at mu-opioid receptors and can cross into the central nervous system, where its buildup enhances sedation and depresses respiration. Morphine-3-glucuronide, while it may also accumulate, is not analgesic and does not drive narcosis or ventilatory depression. Unchanged morphine and no accumulation are less relevant in this context, as the key toxicity in renal impairment comes from the active metabolite that remains in circulation longer due to reduced renal clearance.