Special Topics in Pain: Opioids

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Opioid-Induced Constipation and Bowel Dysfunction: A clinical Guideline.

Author(s): Müller-Lissner, et al.
Journal: Pain Medicine. 2017; 18: 1837-1863. 168 references.
Reprint: Stefan Müller-Lissner, MD, Eisenacherstrasse 103D, 10781 Berlin, Germany. E-mail: stefan@mueller-Lissner.de
Faculty Disclosure: Please see original article for disclosures. Abstracted by N Walea, who has nothing to disclose.
Objective: Review and evaluate the latest advances and newest information in the area of other (unspecified) systems; Review and evaluate the latest advances and newest information in the area of Opioids


Editor’s Note: Opioid induced constipation is not ubiquitous amongst opioid users, but it does have a relatively high prevalence.  Screening for it upon initiation or titration of opioids is reasonable, and there are multiple treatment options as noted below.  Decreasing opioid dose or dosing interval can also help, as can more consistent levels of opioids, such as those found with fentanyl or buprenorphine patches. 

Class: Opioid induced consipation

Constipation is a major untoward effect of opioids but the inhibitor effect of opioid are not confined to the colon. These untoward effects may also affect higher segment of the gastrointestinal tract, leading to the coining of the term "opioid-induced bowel dysfunction" (OIBD).

 An extensive literature search of online databases led to the formulation of a series of statements regarding best practices in management of patients with opioid-induced constipation (OIC) and OIBD, based on the information found during the search. This series of statements are shared below.

The definition of OIC/OIBD is based on a clinical evaluation relating to a change in bowel habits during opioid therapy.

The symptoms of OIC are related to the colon whereas OIBD manifest in symptoms throughout the GI tract. OIBD is a distressing condition that manifests through a variety of different symptoms including vomiting, dry mouth, abdominal pain, gastroesophageal reflux, and constipation.

Opioid receptors are spread throughout the GI tract from the mid-esophagus to rectum and are involved in a variety of cellular functions. Opioid agonists administration results in slowing of normal GI motility, segmentation, increased tone, and uncoordinated motility reflected in, for example, increased transit times. Opioids result in increased absorption and decreased secretions of fluids in the gut leading to dry feces and less propulsive motility. Opioids increase sphincter tone, which may cause symptoms such as Sphincter of Oddi spasms and difficult defecation. Gastroesophageal reflux symptoms in OIBD should be treated as primary reflux disease. Patients with nausea secondary to opioid treatment should be offered dopamine antagonists.

Subjective reports of OIC are based on validated questionnaires, whereas there is no consensus about assessment of OIBD. Objective assessment of OIBD has focused on motility, but there are only a few human studies on opioid effects on secretion and sphincter function. Data on prevalence of OIC differs widely based on the definitions used and origin of the studies, but not on gender.

The type of pure opioid drugs does not influence the prevalence of OIC symptoms. The dose and frequency of opioids influences likelihood of OIC. Transdermal preparations of Fentanyl and Buprenorphine may be associated with lower incidence of OIC than oral opioids. Duration of Opioid Therapy influences the Impact of OIC symptoms.

QoL (quality of life) can be worse due to side effects of opioids. Assessment of QoL in patients with OIC/OIBD can assist therapeutic choices. Nonpharmacological treatments of OIC include dietary recommendations and lifestyle modifications.

The choice of a laxative to treat OIC/OIBD depends on the perceived efficacy and the preference of the patient. Indirect evidence favors bisacodyl, sodium picosulfate, macrogol (polyethelene glycol), and sennosides as first choice. Sugars and sugar alcohols such as lactulose, lactose, and sorbitol should not be used to prevent or treat OIC. Treatment of OIC with new laxatives (prucalopride, lubiprostone) many be promising, however, there are insufficient data to warrant such treatments in OIC patients.

Opioid antagonists counteract the effects of opioids in the human gut on motility, fluid transport and sphincter function. Peripherally acting µ-opioid receptor antagonists (PAMORAs) effectively reduces OIC. Prolonged-release naloxone/oxycodone combination effectively reduces OIC while maintaining equal analgesia to prolonged-release oxycodone alone. Oral naloxegol is effective and safe in reducing OIC in patients with chronic pain. Methylnaltrexone injections can effectively relieve OIC in patients with chronic pain.

Alvimopan is approved in the U.S. for use in hospitalized patients for preventing or decreasing the course of postoperative ileus after bowel resection but it may increase the risk of cardiovascular events. There is some evidence that alvimopan reduces OIC in subjects with chronic opioid intake.

Both laxative and opioid antagonists for OIC have benefits on QoL.

Important Points:
OIBD is an increasing problem due to the wider use of opioids, including the treatment of nonmalignant pain. Current knowledge is certainly insufficient regarding many aspects of OIC, and more so of OIBD. Rather, awareness of the problem is mandatory for the treating physician. As only about half of patients taking opioid experience OIC, a general co-medication with a laxative or an opiate antagonist would be an overtreatment. Prophylaxis could be adjusted to the perceived risks of OIC in a particular patient. PAMORAs clearly have a proven effect on OIC. Whether PAMORAs have advantages over laxatives through the addressing of OIBD, and not only OIC, needs to be shown in randomized double-blind comparative trials.

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