From the Guidelines
Opiates cause constipation by activating enteric mu-receptors, leading to increased tonic non-propulsive contractions, increased colonic fluid absorption, and stool desiccation, resulting in harder stool and less frequent defecation. This effect is mediated by the binding of opioids to mu-receptors in the small intestine and proximal colon, which slows down gut motility and reduces peristalsis 1. The activation of these receptors also increases anal sphincter tone and decreases sensitivity to rectal distension, making it more difficult to have a bowel movement. Additionally, opioids inhibit the secretion of intestinal fluids and digestive enzymes, further contributing to constipation.
Key Mechanisms
- Increased tonic non-propulsive contractions in the small and large intestine
- Increased colonic fluid absorption
- Stool desiccation
- Increased anal sphincter tone
- Decreased sensitivity to rectal distension
- Inhibition of intestinal fluid and digestive enzyme secretion
Management
- Preventative measures: increased fluid intake, dietary fiber, regular exercise
- Prophylactic laxatives: stimulants (senna), osmotic agents (polyethylene glycol), peripherally acting mu-opioid receptor antagonists (naloxegol, methylnaltrexone) specifically designed to treat opioid-induced constipation without affecting pain control, as recommended by the American Gastroenterological Association Institute guideline on the medical management of opioid-induced constipation 1.
Prevalence
Opioid-induced constipation (OIC) is estimated to affect 40%–80% of patients taking chronic opioid therapy, making it a significant concern in clinical practice 1.
From the FDA Drug Label
1.1 Opioid-Induced Constipation in Adult Patients with Chronic Non-Cancer Pain 1.2 Opioid-Induced Constipation in Adult Patients with Advanced Illness 12.1 Mechanism of Action
The mechanism of Opioid-Induced Constipation is not explicitly described in the provided drug label. However, it is implied that Opioids cause constipation, and methylnaltrexone is used to treat it. The exact mechanism by which Opiates cause constipation is not directly stated in the label 2.
From the Research
Opiate-Induced Constipation Mechanism
- Opioids bind to their receptors in the gastrointestinal tract, leading to opioid-induced constipation (OIC) 3, 4, 5.
- This binding causes a change in baseline bowel habit or defecatory patterns following initiation, alteration, or increase of opioid therapy 3.
- OIC is a consequence of the action of opioids on their receptors in the gastrointestinal tract, specifically the μ-opioid receptors in the enteric system 4, 5.
Clinical Consequences of Opiate-Induced Constipation
- OIC can significantly impair patients' quality of life (QOL), causing substantial overall burden, including increases in anxiety and depression, impairments in activities of daily living, low self-esteem, and feelings of embarrassment 5.
- Patients with OIC often experience economic burden, including higher health care costs, more frequent doctor visits, and increased out-of-pocket medication costs 5.
- OIC can lead to patients modifying or discontinuing opioid treatment despite the analgesic benefits 5.
Management of Opiate-Induced Constipation
- Preventive strategies, such as lifestyle changes, should be considered when patients start treatment with opioids 3.
- First-line management includes simple over-the-counter laxatives 3.
- Peripherally acting μ-opioid receptor antagonists (PAMORAs) can provide a targeted approach to OIC management, blocking μ-opioid receptors in the gastrointestinal tract without affecting the central analgesic effects of the opioid 4, 5, 6.
- PAMORAs, such as naldemedine and methylnaltrexone, have shown significant improvements in QOL based on the Patient Assessment of Constipation Symptoms questionnaire relative to placebo 5.