Constipation with opioids

When using opioids, prevent constipation with a Gl stirmJant. 

Digestive system g agonists decrease secretion of stomach acid, reduce gastric motility, and prolong gastric emptying. Pancreatic, biliary, and intestinal secretions are reduced. Intestinal transit is also slowed. Peristaltic movements are reduced, but tone is increased, sometimes causing spasm. As a result, constipation is a frequent problem with opioid use. Bile duct pressure is also increased by opioids. 

The use of opium dates to 4,000 b.c. At that time it was used for medicinal and recreational purposes mainly via inhalation. Today few opium-containing preparations are used, since the activity of opium is largely attributed to its morphine content. The preparations in use today are those that have constipative effects useful for the treatment of diarrhea. Preparations include pantopon, an injectable hydrochloride of opium alkaloids, and paregoric, a camphorated tincture of opium. Paregoric can be used to treat infants with opioid withdrawal signs following in utero exposure to opioids. 

A strategy for controlling pain caused by malignant disease has been outlined and the classic effects that can be associated with opioid administration have been reviewed (6). These include constipation, nausea, sedation, pruritus, urinary retention, myoclonus, and respiratory depression. The latter can be life-threatening. Particular care is needed in opioid-naive individuals, those with compromised respiratory function, and elderly patients. 

Fentanyl is used chronically in the management of major pain in humans. One of the common side effects of therapy with opioids is constipation. However, a recent cohort analysis of a large California HMO looking at the incidence of constipation in patients receiving opioid analgesics showed a low incidence of constipation in the patients receiving fentanyl patches (3.7%). 

Opioid antagonists (Table 7.4), predominantly naloxone, are used clinically to reverse the effects of opiates in overdose or postoperative sedation. Naltrexone, which has oral bioavailability, is used for the treatment of narcotic addiction and alcohol dependence. As discussed below (Section 2.2.2.1), peripherally selective antagonists are being evaluated for treatment of constipation and other gastrointestinal side effects associated with opioid agonist use. 

The decreased gut transit time associated with opioids, when not desired, can cause severe constipation and even bowel obstruction. Patients do not usually develop tolerance to these effects of opioids, even after long-term treatment. Morphine is also associated with spasms in the bile duct and sphincter of Oddi and the bladder. At higher doses, nausea and vomiting related to the chemore-ceptor trigger zone in the fourth ventricle of the brain can be a limiting factor in opioid therapy. 

Hydromorphone binds to p opioid receptors in the central nervous system to produce dose-dependent analgesia. Binding at p receptors is also responsible for many of its its side effects including euphoria, pruritus, nausea, decreased GI motility, and constipation. Respiratory depression, the most troubling adverse event associated with hydromorphone, can be reversed with opioid antagonists such as naloxone. 

In an efficacy and safety trial of BTDS in opioid-exposed subjects with moderate to severe low back pain, the most frequently reported adverse events were those typically associated with opioid therapy (e.g. nausea, headache, vomiting, constipation, somnolence, dizziness) and application-site prittitus, typical of a transdermal delivery system [4]. BTDS treatments were found to be generally well-tolerated and safe. 

Dmg fominlations A novel implant of buprenorphine (Probuphine ) with sustained-release technology has been evaluated in 12 subjects with opioid dependence maintained on sublingual buprenorphine [191. Most of them (92%) had at least one adverse event and 58% had events related to the insertion or removal of the implant. Other adverse events were experienced by 42% and included dizziness, constipation, abdominal pain, implant site reactions, flushing, and pallor. There were no serious events. 

Side effects are similar to those observed with opioids constipation nausea central nervous system depression seizures (in conditions with lower seizure threshold)... 

Patients who are acutely intoxicated with an opioid usually present with miosis, euphoria, slow breathing and slow heart rate, low blood pressure, and constipation. Seizures may occur with certain agents such as meperidine (Demerol ). It is critically important to monitor patients carefully to avoid cardiac/ respiratory depression and death from an excessive dose of opioids. One strategy is to reverse the intoxication by utilizing naloxone (Narcan ) 0.4 to 2 mg IV every 2 to 3 minutes up to 10 mg. Alternatively, the IM/SC route may be used if IV access is not available. Because naloxone is shorter-acting than most abused opioids, it may need to be readministered at periodic intervals otherwise the patient could lapse into cardiopulmonary arrest after a symptom-free interval of reversed... 

The best management of opioid-induced constipation is prevention. Patients should be counseled on proper intake of fluids and fiber, and a laxative should be added with chronic opioid use. 

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