Serotonin syndrome has occurred in patients receiving concurrent antidepressant therapy with selective serotonin reuptake inhibitors (SSRIs) or monoamine oxidase inhibitors, or other medication types (see Interactions below). Convulsive seizures sometimes observed in patients receiving parenteral pethidine on a chronic basis have been attributed to accumulation in plasma of the metabolite norpethidine (normeperidine). Fatalities have occurred following either oral or intravenous pethidine overdose. Interactions
Pethidine has serious interactions that can be dangerous with monoamine oxidase inhibitors (e.g., furazolidone, isocarboxazid, moclobemide, phenelzine, procarbazine, selegiline, tranylcypromine). Such patients may suffer agitation, delirium, headache, convulsions, and/or hyperthermia. Fatal interactions have been reported including the death of Libby Zion. Seizures may develop when tramadol is given intravenously following, or with, pethidine. It can interact as well with SSRIs and other antidepressants, antiparkinson agents, migraine therapy, stimulants and other agents causing serotonin syndrome. It is thought to be caused by an increase in cerebral serotonin concentrations. It is probable that pethidine can also interact with a number of other medications, including muscle relaxants, benzodiazepines, and ethanol. Mechanism of action
Like morphine, pethidine exerts its analgesic effects by acting as an agonist at the μ-opioid receptor.Pethidine is often employed in the treatment of postanesthetic shivering. The pharmacologic mechanism of this antishivering effect is not fully understood, but it may involve the stimulation of κ-opioid receptors.Pethidine has structural similarities to atropine and other tropane alkaloids and may have some of their effects and side effects. In addition to these opioidergic and anticholinergic effects, it has local anesthetic activity related to its interactions with sodium ion channels.
The free base conversion ratio for salts includes 0.87 for the hydrochloride and 0.84 for the hydrobromide. The A, B, and C intermediates in production of pethidine are also controlled, with ACSCN being 9232 for A (with a 6 gram quota) and 9233 being B (quota of 11 grams) and 9234 being C (6 gram quota). It is listed under the Single Convention for the Control of Narcotic Substances 1961 and is controlled in most countries in the same fashion as is morphine. Society and culture
In Raymond Chandlers novel The Long Goodbye (1953), in response to "How is Mrs. Wade? ", police Lieutenant Bernie Ohls answers, "Too relaxed. She must have grabbed some pills. Theres a dozen kinds up there -- even demerol. Thats bad stuff." Harold Shipman once got addicted to pethidine.Danish writer Tove Ditlevsen suffered a lifelong addiction to pethidine since her husband, a dodgy doctor, had injected her a dose as a painkiller.Pethidine is referenced by its brand name Demerol in the song "Morphine" by singer Michael Jackson on his 1997 album Blood on the Dance Floor: HIStory in the Mix. Pethidine was one of several prescription drugs which Michael Jackson was addicted to at the time and the singer describes this in the lyrics of the song with phrases such as "Relax/This wont hurt you" and "Yesterday you had his trust/Today hes taking twice as much".Pethidine is referenced in the television show Broadchurch, season 2, episode 3, as it was given to the character Beth after she has her baby.