Pethidine

Pethidine (USAN) (also referred to as: isonipecaine; lidol; pethanol; piridosal; Algil^®; Alodan^®; Centralgin^®; Demerol^®; Dispadol^®; Dolantin^®; Petidin^® Dolargan^® (in Poland);^[1] Dolestine^®; Dolosal^®; Dolsin^®; Mefedina^®) is a fast-acting analgesic drug. In the United States and Canada, it is more commonly known as meperidine or by its brand name Demerol.^[2]

Pethidine is indicated for the treatment of moderate to severe pain, and is delivered as its hydrochloride salt in tablets, as a syrup, or by intramuscular or intravenous injection. For much of the 20^th century, pethidine was the opioid of choice for many physicians; in 1983 60% of doctors prescribed it for acute pain and 22% for chronic severe pain.^[3] Compared to morphine, pethidine was supposed to be safer and carry less risk of addiction, and to be 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 opioid analgesics have seen it fall out of favor in recent years, for all but a very few, very specific indications.^[4] Several countries, including Australia, have put severe limits on its use or curtailed it outright.^[5] Nevertheless, some physicians continue to use it as a first-line strong opioid.

Pharmacodynamics/Mechanism of Action

Main article: Opioid

Pethidine's efficacy as an analgesic was discovered almost accidentally; it was synthesized in 1939 as an norpethidine.^[6][10]

Pharmacokinetics

  Pethidine is quickly hydrolysed in the liver to glucuronic acid and excreted into the urine.

Interactions

Pethidine has serious interactions that can be dangerous with 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, twitchiness, muscular twitches, and nausea, the repeated administration of pethidine can lead to neurotoxic effects. Pethidine should ideally NOT be administered by the intravenous route as there is a serious risk of triggering histamine release.

References

1. ^ Lekopedia - Dolargan. jestemchory.pl. Retrieved on 2006-08-01.
2. ^ Demerol RxList. Retrieved 19 Jun. 2006.
3. ^ Kaiko, Robert F.; Kathleen M. Foley, Patricia Y. Grabinski, George Heidrich, Ada G. Rogers, Charles E. Inturrisi, Marcus M. Reidenberg (February 1983). "Central Nervous System Excitatory Effects of Meperidine in Cancer Patients". Annals of Neurology 13 (2): 180-185. Wiley Interscience. ISSN: 0364-5134.
4. ^ Donna Wong (2002-03-15). Notes on Meperidine. Wong on Web Papers. Elsevier. Retrieved on 2007-04-13.
5. ^ ^{a b} Davis, Sharon (August 2004). [www.clininfo.health.nsw.gov.au/nswtag/publications/posstats/Pethidinefinal.pdf Use of pethidine for pain management in the emergency department: a position statement of the NSW Therapeutic Advisory Group] (PDF). New South Wales Therapeutic Advisory Group. Retrieved on 2007-01-17.
6. ^ ^{a b c d} Latta, Kenneth S.; Brian Ginsberg, Robert L. Barkin (January/February 2002). "Meperidine: A Critical Review". American Journal of Therapeutics 9 (1): 53-68. Lippincott Williams & Wilkins. ISSN: 1075-2765.
7. ^ Wagner, Larry E., II; Michael Eaton, Salas S. Sabnis, Kevin J. Gingrich (November 1999). "Meperidine and Lidocaine Block of Recombinant Voltage-Dependent Na⁺ Channels: Evidence that Meperidine is a Local Anesthetic". Anesthesiology 91 (5): 1481-1490. Lippincott Williams & Wilkins. ISSN: 0003-3022.
8. ^ ^{a b c} Izenwasser, Sari; Amy Hauck Newman, Brian M. Cox, Jonathan L. Katz (January/February 1996). "The cocaine-like behavioral effects of meperidine are mediated by activity at the dopamine transporter". European Journal of Pharmacology 297 (1-2): 9-17. Elsevier. doi:10.1016/0014-2999(95)00696-6. ISSN: 0014-2999.
9. ^ Lomenzo, Stacey A.; Jill B. Rhoden, Sari Izzenwasser, Dean Wade, Theresa Kopajtic, Jonathan L. Katz, Mark L. Trudell (2005-03-05). "Synthesis and Biological Evaluation of Meperdine Analogs at Monoamine Transporters". Journal of Medicinal Chemistry 48 (5): 1336-1343. American Chemical Society. ISSN: 0022-2623.
10. ^ ^{a b c d} (June 2006) "Demerol: Is It the Best Analgesic?". Pennsylvania Patient Safety Reporting Service Patient Safety Advisory 3 (2). Pennsylvania Patient Safety Authority. Retrieved on 2007-01-16.
11. ^ In Brief. NPS Radar. National Prescribing Service (December 2005). Retrieved on 2007-01-17.
12. ^ Walker, Diana J.; James P. Zacny (June 1999). "Subjective, Psychomotor, and Physiological Effects of Cumulative Doses of Opioid µ Agonists in Healthy Volunteers". The Journal of Pharmacology and Experimental Therapeutics 289 (3): 1454-1464. American Society for Pharmacology and Experimental Therapeutics.
13. ^ Norpethedine half-life. 2002. Australian prescriber[1]