Opioid-induced constipation in chronic noncancer pain

Abstract

PAMORA MNTX and naloxegol and the intestinal chloride channel-2 (ClC-2) activator lubiprostone represent additional possible therapeutic options for the management of OIC in patients with chronic noncancer pain.

Peripherally acting μ-opioid receptor antagonists as treatment options for constipation in noncancer pain patients on chronic opioid therapy

“…The first PAMORA approved by the US Food and Drug Administration (FDA) for OIC in terminally ill patients was subcutaneous methylnaltrexone, which has since been approved for use in patients with chronic noncancer pain 31. Methylnaltrexone bromide (Relistor ® ; Salix Pharmaceuticals, Inc., Raleigh, NC, USA) does not reverse the analgesic effect of opioids nor does it lead to withdrawal symptoms.…”

“…Lubiprostone (Amitiza; Sucampo Pharmaceuticals, Inc., Rockville, MD, USA) is an oral agent in the form of a bicyclic fatty acid that acts as a chloride channel 2 (CIC-2) activator 31. Lubiprostone activates CIC-2 in the gut, increasing intestinal fluid secretion and enhancing transit through the gut without altering sodium and potassium serum concentrations 36.…”

Long-term use of naldemedine in the treatment of opioid-induced constipation in patients with chronic noncancer pain: a randomized, double-blind, placebo-controlled phase 3 study

“…Peripherally acting μ-opioid receptor antagonists (PAMORAs) are a class of drugs that target the mechanism underlying OIC without affecting the centrally mediated analgesic effects of opioids. 32 Peripherally acting μ-opioid receptor antagonists bind to and markedly reduce opioid stimulation of peripheral µ-opioid receptors in the gastrointestinal tract. Naldemedine (also known as S-297995) is a PAMORA approved as a once-daily oral drug for the relief of OIC in adult patients with cancer and those with chronic noncancer pain, including patients with chronic pain related to previous cancer, or its treatment which does not require frequent dosage escalation.…”

Designing Safer Analgesics via μ-Opioid Receptor Pathways

“…In particular, the development of functionally selective κOR agonists targeting peripheral sensory neurons can significantly reduce adverse effects normally mediated through the central nervous system (CNS) [43]. Alternatively, polyethylene glycol (PEG)-conjugated μOR antagonists with increased half-lives [44] cannot penetrate the BBB and alleviate constipation during opioid pain management [44,45]. Although the long-term safety of these new candidates requires further evaluation and clinical studies, these exciting breakthroughs are indeed encouraging in the pursuit of next-generation safer painkillers (see Outstanding Questions).…”