Monoamine oxidase inhibitors neuroleptic drugs

Adverse effects Large doses of meperidine cause tremors, muscle twitches, and rarely, convulsions. The drug differs from opioids in that in large doses it dilates the pupil and causes hyperactive reflexes. Severe hypotension can occur when the drug is administered postoperatively. When used with major neuroleptics, depression is greatly enhanced. Administration to patients taking monoamine oxidase inhibitors (see p. 123) can provoke severe reactions such as convulsions and hyperthermia. Meperidine can cause dependence, and can substitute for morphine or heroin in use by addicts. Cross-tolerance with the other opioids occurs. 

There can be additive hypotensive effects when monoamine oxidase inhibitors are combined with neuroleptic drugs. 

Diphenoxylate is an opiate (schedule V) with antidiarrheal properties. It is usually dispensed with atropine and sold as Lomotil. The atropine is added to discourage the abuse of diphenoxylate by narcotic addicts who are tolerant to massive doses of narcotic but not to the CNS stimulant effects of atropine. Diphenoxylate shonld be used cautiously in patients with obstructive jaundice because of its potential for hepatic coma, and in patients with diarrhea cansed by pseudomembranous colitis because of its potential for toxic megacolon. In addition, it should be used cautiously in the treatment of diarrhea caused by poisoning or by infection by Shigella, Salmonella, and some strains of E. coli because expulsion of intestinal contents may be a protective mechanism. Diphenoxylate should be used with extreme caution in patients with impaired hepatic function, cirrhosis, advanced hepatorenal disease, or abnormal liver function test results, because the drug may precipitate hepatic coma. Because diphenoxylate is structurally related to meperidine, it may cause hypertension when combined with monoamine oxidase inhibitors. As a narcotic, it will augment the CNS depressant effects of alcohol, hypnotic-sedatives, and numerous other drugs, such as neuroleptics or antidepressants that cause sedation. 

Section B (Fig. 17) shows some commonly used drugs which are electroactive. The a-methyltryptamine was detected at + 0.8 V by Marsden (1980) in 5-HT studies. Several monoamine oxidase inhibitors are electroactive, but there is so far no evidence that they can be detected in vivo and, even if they are, it is at potentials sufficiently positive not to interfere with most studies. Chlorpromazine and haloperidol have solution Ep values about + 0.6 V and + 0.7 V, respectively. Clozapine oxidizes at about + 0.4 V. Since neuroleptics (and other drugs) are extensively metabolized by the time they appear in significant concentrations in the CNS, the potentials of the parent compounds may not be too relevant—but no data are available for metabolites. In any event, there is no evidence that any of these drugs are detected in CNS voltammetry. 

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