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Pethidine
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| Systematic (IUPAC) name | |
| Ethyl-1-methyl-4-phenylpiperidine-4-carboxylate | |
| Identifiers | |
| CAS number | 57-42-1 |
| ATC code | N02AB02 |
| PubChem | 4058 |
| DrugBank | APRD00074 |
| Chemical data | |
| Formula | C15H21NO2 |
| Mol. weight | 247.33 |
| Pharmacokinetic data | |
| Bioavailability | variable |
| Protein binding | 65-75% |
| Metabolism | Liver |
| Half life | 3-5 hours |
| Excretion | Renal |
| Therapeutic considerations | |
| Pregnancy cat. | C(AU) C(US) |
| Legal status | S8(AU) Class A(UK) Schedule II(US) |
| Routes | oral, IV, IM |
Pethidine (INN) or meperidine (USAN) (also referred to as: isonipecaine; lidol; operidine; pethanol; piridosal; Algil®; Alodan®; Centralgin®; Demerol®; Dispadol®; Dolantin®; Dolargan® (in Poland)[1]; Dolestine®; Dolosal®; Dolsin®; Mefedina®) is a fast-acting opioid analgesic drug. In the United States, it is more commonly known as meperidine or by its brand name Demerol.
Pethidine is indicated for the treatment of moderate to severe pain, and is delivered as hydrochloride tablets, as a syrup, or by intramuscular or intravenous injection. For much of the 20th century, pethidine was the opioid of choice for many physicians. Compared to morphine, pethidine was supposed to be safer and carry less risk of addiction, and superior in treating the pain associated with biliary spasm or renal colic due to its putative antispasmodic effects. In fact, pethidine is no more effective than morphine at treating biliary or renal pain, and its low potency, short duration of action, and unique toxicity (i.e. seizures, delirium, other neuropsychological effects) relative to other available agents have seen it fall out of favor in recent years, for all but a very few, very specific indications. Nevertheless, some physicians continue to use it as a first-line strong opioid.
Contents |
Mode of action
Main article: Opioid
Pethidine's efficacy as an analgesic was discovered fortuitously; it was synthesized in 1939 as an antimuscarinic agent. Pethidine exerts its analgesic effects by the same mechanism as morphine, by acting as an agonist at the μ-opioid receptor. In addition to its strong opiodergic and anticholinergic effects, it has local anesthetic effects related to its interactions with sodium ion channels. Pethidine's in vitro efficacy as an "antispasmodic" is due to its local anesthetic effects. It does not, contrary to popular belief, have antispasmodic effects in vivo. It has also been associated with cases of serotonin syndrome, suggesting some interaction with serotonergic neurons, but the relationship has not been definitively demonstrated. It is more lipid-soluble than morphine, resulting in a faster onset of action. Its duration of clinical effect is 120-150 minutes. Like other opioid drugs, pethidine has the potential to be both physically and psychologically habituating. The especially severe side effects unique to pethidine among opioids are thought to be primarily due to the action of its metabolite, norpethidine.
Pharmacokinetics
Pethidine is quickly hydrolysed in the liver to pethidinic acid and is also demethylated to norpethidine, which has half the analgesic activity of pethidine but a longer elimination half-life (8-12 hours[2]); accumulating with regular administration, or in renal failure. Norpethidine is toxic and has convulsant and hallucinogenic effects. The toxic effects mediated by the metabolites cannot be countered with opioid receptor antagonists such as naloxone or naltrexone and are probably primarily due to norpethidine's anticholinergic activity; its pharmacology has not been thoroughly explored. The neurotoxicity of pethidine's metabolites is a unique feature of pethidine compared to other opioids. Pethidine's metabolites are further conjugated with glucuronic acid and excreted into the urine.
Interactions
Pethidine has serious interactions that can be dangerous with MAOIs (e.g. furazolidone, isocarboxazid, linezolid, moclobemide, phenelzine, procarbazine, selegiline, tranylcypromine, naltrexone, ritonavir, and sibutramine). Such patients may suffer agitation, delirium, headache, convulsions, and/or hyperthermia. It is thought to be caused by an increase in cerebral serotonin concentrations. It is possible that Pethidine can also interact with a number of other medications, including muscle relaxants, some antidepressants, benzodiazepines, and alcohol.
Pethidine is also relatively contraindicated for use when a patient is suffering from liver, or kidney disease, has a history of seizures or epilepsy, has an enlarged prostate or urinary retention problems, or suffers from hyperthyroidism, asthma, or Addison's disease.
Adverse effects
Main article: Opioid
In addition to the adverse effects common to all opioids, such as constipation, dry mouth, lightheadedness, itchiness, muscular twitches, and nausea, the repeated administration of pethidine can lead to neurotoxic effects.
References
- Demerol RxList. Retrieved 19 Jun. 2006.
- ^ Lekopedia - Dolargan. jestemchory.pl. Retrieved on 2006-08-01.
- ^ Norpenthedine half-life. 2002. Australian prescriber[1]
