MORPHINE: PHARMACOLOGY
Morphine is the strong opioid drug of choice for the management of patients with cancer who have moderate or severe pain for the following reasons:

• wide therapeutic range
• efficacy by many routes of administration
• reliability
• availability
• low cost

Pharmacology-Morphine is well absorbed from all sites of administration with the possible exception of the buccal and sublingual routes which have not been extensively studied. The plasma half-life of morphine is 2-3 hours and is unaffected by chronic usage. The effective duration of action approximates four hours, a little less after intravenous injection. Morphine is metabolised predominantly in the liver, mainly to morphine-3-glucuronide (M3G) and
morphine-6-glucuronide (M6G). M6G is a potent opioid receptor agonist and may have an important role in the clinical effect and toxicity of morphine; M3G probably has no significant analgesic action. The detection of increased levels of M6G in the cerebrospinal fluid during chronic administration possibly explains the superior analgesia seen with repeated administration compared to single doses.
The glucuronide metabolites are excreted in the urine and renal impairment, including that which occurs normally in old age, may lead to accumulation of M6G. Increased plasma and cerebrospinal concentrations of M6G have been associated with increased neurotoxicity. Liver disease is not reported to alter morphine pharmacokinetics, but care must be taken if there is severe hepatic dysfunction with encephalopathy. The increased sedation which may occur when morphine is administered with other drugs which have a central depressant action is due to an additive effect rather than altered pharmacokinetics.
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