Opioid antagonists for prevention and treatment of opioid-induced gastrointestinal effects

Curr Opin Anaesthesiol. 2010 Oct;23(5):616-22. doi: 10.1097/ACO.0b013e32833c3473.

Abstract

Purpose of review: The therapeutic action of opioid analgesics is compromised by peripheral adverse effects, among which constipation is the most disabling as laxatives often fail to provide satisfactory relief. This review highlights recent advances in the specific control of opioid-induced constipation by opioid receptor antagonists with limited systemic bioavailability or a peripherally restricted site of action.

Recent findings: The specific management of opioid-induced bowel dysfunction is currently based on three drug entities: oral alvimopan for the shortening of postoperative ileus associated with opioid-induced pain control after bowel resection, subcutaneous methylnaltrexone for the reduction of opioid-induced constipation in patients with advanced illness, and a fixed combination of oral prolonged-release naloxone with prolonged-release oxycodone for the treatment of noncancer and cancer pain. All three drug entities have been shown to attenuate opioid-induced motor stasis in the gut with a favorable adverse effect profile, while the analgesic effect of opioids remains unabated.

Summary: The availability of opioid receptor antagonists with restricted access to the central nervous system provides a novel opportunity to specifically control opioid-induced constipation and other peripheral adverse effects of opioid analgesics. Further studies are needed to evaluate the long-term efficacy, safety and cost-effectiveness of this approach.

Publication types

  • Review

MeSH terms

  • Analgesics, Opioid / adverse effects*
  • Biological Availability
  • Gastrointestinal Diseases / chemically induced*
  • Gastrointestinal Diseases / drug therapy*
  • Gastrointestinal Diseases / epidemiology
  • Gastrointestinal Diseases / prevention & control
  • Humans
  • Narcotic Antagonists / pharmacokinetics
  • Narcotic Antagonists / therapeutic use*
  • Peripheral Nervous System / drug effects

Substances

  • Analgesics, Opioid
  • Narcotic Antagonists