Table 5.
Pharmacological management of opioid-induced bowel dysfunction
| Treatment | Pharmacological mechanisms | Drugs |
|---|---|---|
| Prokinetics, D2 receptor antagonists | Improve motility of the upper GI tract, increase lower esophageal sphincter tone | Metoclopramide, domperidone |
| Improve motility of the whole GI tract due to inhibition of acetylcholinesterase | Itopride | |
| Prokinetics, 5-HT4 receptor agonist | Improve GI motility | Tegaserod, cisapride – both drugs withdrawn due to cardiotoxicity Prucalopride |
| Prokinetics, chloride channels agonists | Stimulation of intestinal fluid secretion inducing softer stools, increased colonic transit and stool frequency | Lubiprostone |
| Prokinetics activating guanylate cyclase C | Stimulation of GI secretion and transit – increase stool frequency, stool weight, and ease stool passage | Linaclotide |
| Laxatives, stimulants | Activation of myenteric plexus in the colon – promotion of propulsive motility | Sennosides, bisacodyl |
| Laxatives – osmotic agents: saccharines (sugar alcohols) | Metabolism to short-chain fatty acids by gut bacteria | Lactulose, sorbitol |
| Laxatives – osmotic agents: macrogol | Decrease GI transit time | Polyethylene glycol 3350 |
| Laxatives – osmotic agents: magnesium and sodium salts | Secretion of fluid into intestinal lumen | Magnesium hydroxide, sodium biphosphate |
| Laxatives – detergents | Increase GI secretion and decrease surface tension | Docusate |
| Opioid receptor agonists + opioid receptor antagonists | Targeting peripheral µ-opioid receptors, without affecting analgesia due to naloxone inactivation in the liver | Combined prolonged-release oxycodone/prolonged-release naloxone tablets |
| Purely peripheral acting µ-opioid receptor antagonists | Targeting of peripheral of µ-opioid receptor, without affecting analgesia due its inability to cross the blood–brain barrier | Methylnaltrexone, naloxegol Alvimopan – approved in the US only to accelerate the time to upper and lower GI recovery after partial large or small bowel resection surgery with primary anastomosis |
Notes: Adapted from Rauck RL. Treatment of opioid-induced constipation: focus on the peripheral μ-opioid receptor antagonist methylnaltrexone. Drugs. 2013; 73(12):1297–1306.44
Abbreviation: GI, gastrointestinal.