Morphine is a prototype opioid that is less lipophilic (less blood-brain barrier penetration) than the synthetic opioids and therefore has a slower onset of action (within 20 minutes) but a longer analgesic duration (4 to 6 hours and up to 7 hours for morphine-6-glucoronide). It is metabolized in the liver to morphine-6-glucoronide (active) and morphine-3-glucoronide (inactive but may contribute to CNS stimulation). Morphine-6-glucoronide is a potent, active metabolite of morphine that produces ongoing analgesia, severe, prolonged and potentially delayed respiratory depression, and potent gastrointestinal transit inhibition. Since morphine-6-glucoronide is excreted by the kidney, it may accumulate in patients with renal insufficiency; therefore, morphine should be used with caution in patients with renal insufficiency. Fortunately, as with morphine, the respiratory depressive properties of morphine-6-glucoronide can be reversed with naloxone.
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