Interactions With Other Drugs

Severe reactions may follow the administration of meperidine to patients being treated with MAO inhibitors. An excitatory reaction ("serotonin syndrome") with delirium, hyperthermia, headache, hyper- or hypotension, rigidity, convulsions, coma, and death may be due to the ability of meperidine to block neuronal reuptake of 5-HT and the resulting serotonergic overactivity. Therefore, meperidine and its congeners should not be used in patients taking MAO inhibitors. Potentiation owing to inhibition of hepatic CYPs also can be observed in patients taking MAO inhibitors, necessitating a reduction in the doses of opioids.

Chlorpromazine and tricyclic antidepressants increase the respiratory-depressant and sedative effects of meperidine. Increased respiratory depression is not seen with concomitant use of diazepam. Treatment with phenobarbital or phenytoin increases systemic clearance and decreases oral bioavailability of meperidine; this is associated with an elevation of the plasma concentration of normeperidine. Concomitant administration of amphetamine has been reported to enhance the analgesic effects of meperidine and its congeners while counteracting sedation.

THERAPEUTIC USES Meperidine is used for analgesia. Single doses of meperidine appear to be effective in the treatment of postanesthetic shivering. Meperidine, 25-50 mg, is used frequently with antihistamines, glucocorticoids, acetaminophen, or nonsteroidal anti-inflammatory drugs (NSAIDs) to prevent or ameliorate infusion reactions that accompany the intravenous administration of amphotericin B, aldesleukin (interleukin-2), trastuzumab, and alemtuzumab.


Diphenoxylate is a meperidine congener that is approved for the treatment of diarrhea (see Chapter 37). Diphenoxylate hydrochloride is available only in combination with atropine sulfate (lomotil, others). The recommended daily dosage of diphenoxylate for the treatment of diarrhea in adults is 20 mg in divided doses. Difenoxin (motofen), a metabolite of diphenoxylate, has actions similar to those of the parent compound.


Loperamide (imodium, others), like diphenoxylate, is a piperidine derivative; it penetrates poorly into the CNS. Loperamide slows GI motility by effects on the circular and longitudinal muscles of the intestine, presumably via interactions with opioid receptors in the intestine. In controlling chronic diarrhea, loperamide is as effective as diphenoxylate, and little tolerance develops.

Fentanyl and Congeners

Fentanyl is a synthetic opioid related to the phenylpiperidines. The actions of fentanyl and congeners are similar to those of other j-receptor agonists. Fentanyl is a popular anesthetic because of its relatively short time to peak analgesic effect, rapid termination of effect after small bolus doses, and cardiovascular safety (see Chapter 13).

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