Opioid gastrointestinal effects

Major gastrointestinal effects include decreased gut motility and changes in secretion of gastric and intestinal fluids. Morphine and most p receptor agonists cause pupillary constriction. Some tolerance to this effect may develop, but addicts with high opioid levels will still have miosis. Respiratory depression is the usual cause of death from opioid overdose. 

Although opioids have been used for thousands of years for their analgesic, euphoric, antitussive, and gastrointestinal effects, only relatively recently has their impact on... 

Opioids are used for the management of both acute and chronic pain. However, in addition to pain relieve, opioids have a wide variety of other effects. Some of these side effects can be particularly harmful, such as respiratory depression and the induction of dependency. Gastrointestinal effects like obstipation, nausea and vomiting can limit their use. 

The antidiarrheal activity of codeine results from two actions. First, there is a decrease in the propulsive contractile activity of the small and large intestines, which delays the forward movement of the contents of the intestines. Second, codeine causes an increase in the absorption of water from the intestinal contents. These gastrointestinal effects are mediated by specific opioid receptors in the gut (as we will see in... 

Diclofenac, a derivative of phenylacetic acid, is equipotent as an inhibitor of COX-1 and COX-2. In addition to prostaglandin inhibition a central analgesic action of diclofenac mediated by endogenous opioid peptides has been demonstrated. It can be administered orally, intramuscularly or intravenously, and is effective as a postoperative analgesic in a dose of 75-150 mg. The risks of adverse gastrointestinal effects is moderate and diclofenac does not appear to increase blood loss during or after surgery. 

Naltrexone Nonselective competitive antagonist of opioid receptors Reduced risk of relapse in individuals with alcoholism Available as an oral or long-action parenteral formulation Toxicity Gastrointestinal effects and liver toxicity will precipitate a withdrawal reaction in individuals physically dependent on opioids and will prevent the analgesic effect of opioids... 

Diarrhea from almost any cause can be controlled with the opioid analgesics, but if diarrhea is associated with infection such use must not substitute for appropriate chemotherapy. Crude opium preparations (eg, paregoric) were used in the past to control diarrhea, but now synthetic surrogates with more selective gastrointestinal effects and few or no CNS effects, eg, diphenoxylate or loperamide, are used. Several preparations are available specifically for this purpose (see Chapter 62). 

To add a further complication to the understanding of ways in which the opioids act, it now appears that the mu receptors may be further subdivided into fi and /(2 subtypes, the former being high-affinity receptors that mediate supraspinal analgesia, while the latter are of relatively low affinity and are involved in respiratory depression and in the gastrointestinal effects of the agonists. 

GASTROINTESTINAL EFFECTS OF ENKEPHALIN DEGRADING ENZYME INHIBITORS ROLE OF DELTA OPIOID RECEPTOR IN THE ANTISECRETORY EFFECT OF TIORFAN... 

Gastrointestinal effects Constipation occurs through decreased intestinal peristalsis, which is probably mediated by effects on opioid receptors in the enteric nervous system. This powerful action is the basis for the clinical use of these drugs as antidiarrheal agents. 

Comparative studies Tapentadol, a centrally acting p opioid receptor agonist and a noradrenaline reuptake inhibitor, has been compared with oxycodone in the management of moderate to severe chronic osteoarthritis in 1030 patients who were randomized to tapentadol ER 100-250 mg bd, oxycodone CR 20-50 mg bd, or placebo [181. Tapentadol ER was associated with less nausea and vomiting (23% versus 41%) and constipation (19% versus 37%) than oxycodone CR. Dropouts were also more conunon with oxycodone CR (43% versus 19%), mainly because of gastrointestinal effects. Tapentadol ER was better tolerated than oxycodone CR. 

Tapentadol provides high analgesic efficacy that is comparable to classic opioids, but is associated with unexpectedly improved gastrointestinal tolerability [4,5,6,7j. Its two mechanisms of action appear to be additive and provide an opioid-sparing effect while maintaining effective analgesia. The efficacy and safety of various doses of tapentadol IR compared... 

Opioids are easily absorbed subcutaneously and intramuscularly, as well as from the gastrointestinal tract, nasal mucosa (e.g., when heroin is used as snuff), and lung (e.g., when opium is smoked). About 90% of the excretion of morphine occurs during the first 24 hours, but traces are detectable in urine for more than 48 hours. Heroin (diacetyhnorphine) is hydrolyzed to monoacetylmorphine, which is then hydrolyzed to morphine. Morphine and monoacetylmorphine are responsible for the pharmacologic effects of heroin. Heroin produces effects more rapidly than morphine because it is more lipid soluble and therefore crosses the blood-brain barrier faster. In the urine, heroin is detected as free morphine and morphine glucuronide (Gutstein and Akil 2001 Jaffe et al. 2004). 

Mecfianism of Action An opioid agonist that contains many narcotic alkaloids including morphine. It inhibits gastric motility due to its morphine content. Therapeutic Effect Decreases digestive secretions, increases gastrointestinal (GI) muscle tone, and reduces Gl propulsion. 

The answer is c. (Hardman, p 527. Katzung, p 516.) Naloxone is a pure opioid antagonist at the (1, K, and 5 receptors. j,-receptor stimulation causes analgesia, euphoria, decreased gastrointestinal (Gl) activity, miosis, and respiratory depression. K-receptor stimulation causes analgesia, dysphoria, and psychotomimetic effects. 5-receptor stimulation is not fully understood in humans, but is associated with analgesia and antinociception for thermal stimuli. 

The 5-HT3 receptor is the only monoamine neurotransmitter receptor that functions as a lig-and-gated ion channel, controlling the flux of Na-i- and K+ ions. 5-HT3 receptors are located on parasympathetic nerve terminals in the gastrointestinal tract, and high densities are found in areas of the brain associated with the emetic response, such as the area postrema. The antiemetic effects of 5-HT3 antagonists, such as ondansetron, result from actions at these sites. 5-HT3 receptors in the dorsal horn of the spinal cord have been implicated in nociception and development of new 5-HT3 receptor-related compounds may have potential as non-opioid, non-addictive analgesics. 

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