In treating chronic and
acute pain,
opioids are widely used. Although they do provide
analgesia, their usage does come with adverse events (AEs). One of the most burdensome is
opioid-induced bowel dysfunction, and more specifically
opioid-induced constipation (OIC). The pathogenesis of these AEs is well known as the consequence of the action of
opioids on m-receptors in the enteric nervous system. In recent years, medicines counteracting this specific action at the receptors have been registered for clinical use: the peripherally acting μ-
opioid receptor antagonists (PAMORAs). The knowledge of their comparative efficacy and tolerability is very important for physicians and patients in
opioid therapy. This systematic review of the existing literature on PAMORAs aimed to study the relative clinical advantages and disadvantages. The most important data banks, including "PubMed," "Embase," "CT.gov," "ICTRP" and "CINAHL" were used to find the published material on PAMORAs. The selected publications were examined to systematically analyze the efficacy and safety of the four existing PAMORAs. All of the medications are superior to placebo in reducing OIC. There are few published data on
alvimopan used to treat OIC, and it is only indicated for the treatment of post-abdominal surgery
ileus.
Methylnaltrexone is studied mainly in its subcutaneous (SC) formulation. When used in its oral formulation, it seems more rapid than
naloxegol and placebo in the reduction of OIC.
Naldemedine is able to produce more spontaneous bowel movements (SBMs) when compared to
alvimopan and
naloxegol. Tolerability was found to be similar for all of them. In particular, they affect the gastrointestinal tract (GI), with
flatulence and
diarrhea, especially at high dosages. For some of them,
nasopharyngitis and
abdominal pain were observed as treatment adverse effects (TEAs). Several cardiovascular TEAs were reported after
methylnaltrexone use, but it is not clear whether they were consequences of the
drug or related to the general conditions of the patients. Considering the existing data,
naloxegol and
naldemedine seem to be the best choices, with a higher number of spontaneous bowel movements following
naldemedine administration.