Morphine

PHARMACOLOGY

Opioids such as morphine act at opioid receptors which are found both within the CNS and peripherally. Metabolism occurs mainly in the liver but can occur in other organs, including the CNS. The major metabolites of morphine are M3G and M6G. In the setting of renal failure morphine metabolites can accumulate and lead to toxicity.

Morphine may be given orally, rectally, buccally, SC, IM and intraspinally. The PO:SC/IV morphine ratio is 2:1. Morphine oral preparations come in short-acting as well as sustained release preparations.

Time to peak plasma concentration: 15-60 minutes PO (short acting preparations); 10-20 minutes IM/SC
Duration of action: 3-6 h (short acting preparations); 8-12-24 h (sustained release preparations)
Plasma ½ life: 1.5-4.5 h PO (short acting preparations)

DOSING

  • A dose of morphine 2.5 mg regularly q4h PO (or 1 to 2 mg SC/IV) and a breakthrough dose every hour, as required is suitable for an opioid-naive patient (see Breakthrough or Rescue Doses of Morphine). Further titration will be required and the effective dose will vary.
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  • Starting doses for opioid naïve infants less than 6 months: 0.01 mg/kg q4h SC/IV, or 0.02 mg/kg q4h PO
  • Starting dose for opioid naïve infants/children more than 6 months: 0.02 mg/kg q4h SC/IV, or 0.04 mg/kg q4h PO

UNWANTED EFFECTS

  • Common: constipation, dry mouth, sweating
  • Common (usually temporary): sedation, nausea/vomiting
  • Rare: pruritis/urticaria, urinary retention, hallucinations/delirium, respiratory depression

PITFALLS/CONCERNS

  • A laxative should be prescribed routinely when a patient is on an opioid
  • An anti-emetic should be ordered at least prn for use during the first week when starting opioid therapy (this side-effect usually resolves, however, over time)
  • Hepatic failure severe enough to increase the prothrombin time may result in an increased plasma half-life of morphine
  • Warn patients about the possibility of initial drowsiness
  • In the setting of renal failure, accumulation of morphine metabolites can sometimes occur causing opioid neurotoxicity

NOTE

This information is drawn from a number of sources (see below). The reader is encouraged to access these and other relevant literature for more detail. As always, sound clinical judgment should be used in individual clinical cases. In particular, it should be remembered that there may be significant variation in the pharmokinetics of a drug resulting from a number of factors, including the individual patient’s metabolism/disease status and how the medication has been formulated.

SOURCES/REFERENCES

  1. Brunton LL, Lazo JS, Parker KL, editors. Goodman and Gilman’s: the pharmacological basis of therapeutics. 11th ed. McGraw-Hill Professional; 2006.
  2. Twycross R, Wilcock A. Palliative care formulary. 3rd ed. Radcliffe Medical Press Ltd; 2008.
  3. Repchinsky C, editor. Compendium of pharmaceuticals and specialties (CPS): the Canadian drug reference for health professionals. 44th ed. Canadian Pharmacists Association; 2009.
  4. Goldman A, Hain R, Liben S. Oxford textbook of palliative care for children. 1st ed. Oxford University Press; 2006.

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