Morphine

Morphine is widely used in critical care. Glucuronidation of morphine produces two metabolites, morphine-3-glucuronide and morphine-6-glucuronide.

The concentrations of morphine-3-glucuronide and morphine-6-glucuronide may be up to 10 times and 100 times respectively the concentration of morphine in the plasma. Morphine-3-glucuronide tends to antagonize morphine, and morphine-6-glucuronide is up to 10 times more effective than morphine in tests of analgesia. The metabolites depend on glomerular filtration and accumulate in renal failure. This is a significant drawback in critical care patients as it may result in prolonged weaning, increased morbidity, and increased costs. Multicompartmental pharmacokinetic data are not available for morphine. Following titration (front-loading), the elimination half-life (approximately 3 h) is used to calculate the approximate infusion rate as the dose of morphine required in a 3-h period is half the front-loading dose. Suboptimal analgesia requires retitration as adjustment of the infusion alone requires four to five half-lives to steady state.

Sleep Apnea

Sleep Apnea

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