Morphine antidiarrheal effects

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... 

Peripheral effects concern the motility and tonus of gastrointestinai smooth muscie segmentation is enhanced, but propulsive peristalsis is inhibited. The tonus of sphincter muscles is raised markedly. In this fashion, morphine elicits the picture of spastic constipation. The antidiarrheic effect is used therapeutically (ioperamide, p. 

Diphenoxylate Diphenoxylate is used to treat diarrhea. It is too insoluble to escape the Gl tract. Like morphine, it causes constipation, but diphenoxylate fails to produce analgesia. Antidiarrheal effects can be blocked by narcotic antagonists (Table 3.6). 

A not uncommon side effect observed with morphine and some of the other narcotic analgesics is constipation due to decreased motility of the gastrointestinal tract. It proved possible to so modify pethidine as to retain the side effect at the expense of analgesic activity. Relief of diarrhea, it will be realized, is a far from trivial indication. Alkylation of the anion from diphenylacetonitrile (95) with ethylene dibromide gives the intermediate, 96. Alkylation of normeperidine (81) with that halide affords diphenoxylate (97), an antidiarrheal agent. 

Opium Street Names Auntie Emma, big O. black stuff, block, gum, hop, ope, tar (brand generic called tincture of opium, laudanum, paregoric (CIII), B O suppositories [CIII]) Use Some medical uses (antidiarrheal, antitussive, antispas-modic) illegally used to produce morphine and h oin can be swallowed or smoked Actions Narcotic contains morphine Effects Pain relief, euphoria, drowsiness/N, constipation, confusion, sedation, resp dqjression and arrest, tol -ance, addiction, unconsciousness, coma, death... 

Inhibition of intestinal peristalsis rates among one of the more common effects of morphine that are not directly related to its analgesic activity. The finding that meperidine (21-4) shares this effect led to the development of a highly substituted derivative, diphenoxilate (22-3), that also inhibits intestinal motility and thus acts as an antidiarrheal agent. The side chain in (22-3) is prepared by alkylation of the anion from diphenylacetonitrile with 1,2-dibromoethane to give the bromoethyl... 

In addition to modifications of the morphine molecule, many purely synthetic analgesics have been produced, the first of these, pethidine (meperidine), having been synthesized in 1939 in an attempt to make a substitute for atropine (276). As in the case of heroin, pethidine was at first thought to be nonaddictive. It has been followed by a hundred or so other compounds of several different types, but, as with the morphine derivatives, none, with the possible exception of pentazocine, has been found to have analgesic without addictive properties. However, it seems that the two effects may not be entirely inseparable, as diphenoxylate, which has come into use as an antidiarrheal drug, has been found to possess the power to cause addiction but no analgesic action at all (277). 

Loperamide Loperamide (imodium, imodium a-d, others), a piperidine butyramide derivative with -receptor activity, is an orally active antidiarrheal agent. The drug is 40-50 times more potent than morphine as an antidiarrheal agent and penetrates the CNS poorly. It increases small intestinal and mouth-to-cecum transit times. Loperamide also increases anal sphincter tone, an effect that may be of therapeutic value in some patients who suffer from anal incontinence. In addition, loperamide has antisecretory activity against cholera toxin and some forms of Escherichia coli toxin. 

Observational studies Tincture of opium is a preparation of powdered opium, which contains morphine, codeine, papaverine, and alcohol. It is used as an antidiarrheal agent, to treat neonatal abstinence syndrome, in the management of pain, and traditionally for the management of opioid dependency in some Asian countries. In an open study, opium-dependent subjects were allocated to three different doses of tincture of opium twice a day 10 ml (6.66 mg morphine equivalents n = 13), 20 ml (13.3 mg morphine equivalents n = 8), and 30 ml (20 mg morphine equivalents n = 11) [1 j. In all the subjects tincture of opium effectively suppressed withdrawal symptoms without causing significant adverse effects. 

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