Opioids antidiarrheal activity

Diphenoxylate + Atropine (Lomotil, Lonox) [C V] [Opioid Antidiarrheal] Uses D Action Constipating m CTidine congener, X GI motihty Dose Adults. Initial, 5 mg PO tid—qid until controlled, then 2.5-5 mg PO bid 20 mg/d max Peds >2 y. 0.3-0.4 mg/kg/24 h (of diphenoxylate) bid-qid, 10 mg/d max Caution [C, +] Contra Obstructive jaundice, D d/t bacterial Infxn children <2 y Disp Tabs, Liq SE Drowsiness, dizziness, xCTostomia, blurred vision, urinary retention, constipation Interactions T Effects W/ CNS depressants, opioids, EtOH, T risk HTN crisis W7 MAOIs EMS Monitor for Sxs of electrolyte disturbances and hypovolemia d/t D OD May cause Szs, hypotension, and anticholinergic effects (xerostomia [dry mouth], urine retention, flushed skin) activated charcoal may be effective for OD... 

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... 

A. Diphenoxylate is an opioid analog of meperidine. It is metabolized to difenoxin, which has fivefold the antidiarrheal activity of diphenoxylate. Both agents have opioid effects (see p 286) in overdose. 

Berberine is currently being used to treat gastrointestinal-related medical disorders due to infections including bacterial diarrhea caused by Vibrio cholerae and Escherichia coli and intestinal parasites. The mechanism of the antidiarrheal activity of berberine has not been described yet. According to the study performed by Baker et al., berberine significantly inhibits myoelectric activity and transit of the small intestine that appears to be partially mediated by opioid and a-adrenergic receptors, concluding that the antidiarrheal properties of berberine may be mediated, at least in part, by its ability to delay small intestinal transit [67]. 

Opioids. Activation of opioid receptors in the enteric nerve plexus results in inhibition of propulsive motor activity and enhancement of segmentation activity. This antidiarrheal effect was formerly induced by application of opium tincture (paregoric) containing morphine. Because of the CNS effects (sedation, respiratory depression, physical dependence), derivatives with peripheral actions have been developed. Whereas diphenoxylate can still produce clear CNS effects, loperamide does not Lullmann, Color Atlas of Pharmacology... 

As previously noted, opioids have significant constipating effects (see Chapter 31). They increase colonic phasic segmenting activity through inhibition of presynaptic cholinergic nerves in the submucosal and myenteric plexuses and lead to increased colonic transit time and fecal water absorption. They also decrease mass colonic movements and the gastrocolic reflex. Although all opioids have antidiarrheal effects, central nervous system effects and potential for addiction limit the usefulness of most. 

Kappa receptor activation does not appear to be responsible for dependence, euphoria, or effects on smooth muscle. Increases in cerebral blood flow and (possibly) increased intracranial pressure result from the respiratory depressant actions of opioid analgesics. The latter effects are due to increased arterial PrOj, which results from mu receptor inhibition of the medullary respiratory center. However, the activation of kappa receptors contributes to analgesia at the spinal level and is probably responsible for sedative actions of the opioids. The answer is (D). Codeine and possibly nalbuphine could decrease gastrointestinal peristalsis but not without marked side effects (and a prescription). Dextromethorphan is a cough suppressant. The other two drugs listed are opioids with antidiarrheal actions. Diphenoxylate is not available over-the-counter since it is a constituent of a proprietary combination that includes atropine sulfate (Lomotil). Loperamide is available over-the-counter. The answer is (D). 

E. Antidiarrbeal Agents The most effective antidiarrheal drugs are the opioids and derivatives of opioids that have been selected for maximal antidiarrheal and minimal CNS effect. Of the latter group, the most important are diphenoxylate and loperamide, meperidine analogs with very weak analgesic effects. Difenoxin, the active metabolite of diphenoxylate, is also available as a prescription medication. Diphenoxylate is formulated with antimuscarinic alkaloids to reduce the already minimal likelihood of abuse loperamide is formulated alone and sold over the counter as such. 

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