Title:Non-Analgesic Effects of Opioids: Management of Opioid-Induced Constipation by Peripheral Opioid Receptor Antagonists: Prevention or Withdrawal?
Volume: 18
Issue: 37
Author(s): Peter Holzer
Affiliation:
Keywords:
Methylnaltrexone, naloxone, opioid analgesics, opioid-induced bowel dysfunction, opioid-induced constipation, oxycodone;
prolonged-release formulation, withdrawal, laxatives, placebo-controlled trials, peripheral opioid receptor antagonists (PORAs).
Abstract: The therapeutic action of opioid analgesics is compromised by peripheral adverse effects among which opioid-induced constipation
(OIC) is the most disabling, with a prevalence reported to vary between 15 and 90 %. Although OIC is usually treated with laxatives,
there is insufficient clinical evidence that laxatives are efficacious in this indication. In contrast, there is ample evidence from double-
blind, randomized and placebo-controlled trials that peripheral opioid receptor antagonists (PORAs) counteract OIC. This specific
treatment modality is currently based on subcutaneous methylnaltrexone for the interruption of OIC in patients with advanced illness, and
a fixed combination of oral prolonged-release naloxone with prolonged-release oxycodone for the prevention of OIC in the treatment of
non-cancer and cancer pain. Both drugs counteract OIC while the analgesic effect of opioids remains unabated. The clinical studies show
that more than 50 % of the patients with constipation under opioid therapy may benefit from the use of PORAs, while PORA-resistant
patients are likely to suffer from non-opioid-induced constipation, the prevalence of which increases with age. While the addition of
naloxone to oxycodone seems to act by preventing OIC, the intermittent dosing of methylnaltrexone every other day seems to stimulate
defaecation by provoking an intestinal withdrawal response. The availability of PORAs provides a novel opportunity to specifically control
OIC and other peripheral adverse effects of opioid analgesics (e.g., urinary retention and pruritus). The continuous dosing of a PORA
has the advantage of few adverse effects, while intermittent dosing of a PORA can be associated with abdominal cramp-like pain.
