Editing Pethidine (section)

{{Short description|Opioid analgesic}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{about|the analgesic drug also sold under the trade name Dolantin|the anticonvulsant sold under the trade name Dilantin|phenytoin}}
{{Drugbox
| Watchedfields = changed
| class = [[Opioid]]
| verifiedrevid = 464199592
| IUPAC_name = Ethyl 1-methyl-4-phenylpiperidine-4-carboxylate
| USAN = Meperidine
| image = Pethidine2DACS.svg
| image_class = skin-invert-image
| width = 120px
| image2 = Pethidine-PM3-based-on-xtal-1974-3D-balls.png
| width2 = 200px
| tradename = Demerol, others
| pregnancy_AU = C
| pregnancy_US = C
| legal_AU = S8
| legal_BR = A1
| legal_BR_comment = <ref>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-03-31 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=2023-08-03 |access-date=2023-08-16 |publisher=[[Diário Oficial da União]] |language=pt-BR |publication-date=2023-04-04}}</ref>
| legal_CA = Schedule I
| legal_DE = Anlage III
| legal_NZ = Class B
| legal_UK = Class A
| legal_US = Schedule II
| legal_UN = N I
| dependency_liability = High
| addiction_liability = High<ref>{{cite book |vauthors=Bonewit-West K, Hunt SA, Applegate E |title=Today's Medical Assistant: Clinical and Administrative Procedures |date=2012 |page=571 |publisher=Elsevier Health Sciences |isbn=9781455701506 |url=https://books.google.com/books?id=YalYPI1KqTQC&pg=PA571 |access-date=20 August 2019 |archive-date=10 January 2023 |archive-url=https://web.archive.org/web/20230110030031/https://books.google.com/books?id=YalYPI1KqTQC&pg=PA571 |url-status=live }}</ref>
| routes_of_administration = [[Oral administration|By mouth]], [[intravenous]], [[intramuscular injection|intramuscular]], [[intrathecal]],<ref>{{cite journal | vauthors = Ngan Kee WD | title = Intrathecal pethidine: pharmacology and clinical applications | journal = Anaesthesia and Intensive Care | volume = 26 |issue = 2 | pages = 137–146 | date = April 1998 | pmid = 9564390 | doi = 10.1177/0310057X9802600202 | doi-access = free}}</ref> [[subcutaneous injection|subcutaneous]], [[epidural administration|epidural]]<ref>{{cite journal | vauthors = Ngan Kee WD | title = Epidural pethidine: pharmacology and clinical experience | journal = Anaesthesia and Intensive Care | volume = 26 | issue = 3 | pages = 247–255 | date = June 1998 | pmid = 9619217 | doi = 10.1177/0310057X9802600303 | doi-access = free}}</ref>
| bioavailability = 50–60% (Oral), 80–90% (Oral, in cases of hepatic impairment)
| protein_bound = 65–75%
| metabolism = [[Liver]]: [[CYP2B6]], [[CYP3A4]], [[CYP2C19]], [[Carboxylesterase 1]]
| metabolites = • [[Norpethidine]]<br /> • [[Pethidinic Acid]]<br /> • others
| elimination_half-life = 2.5–4 hours, 7–11 hours (liver disease)
| excretion = Renal
| IUPHAR_ligand = 7221
| ATC_prefix = N02
| ATC_suffix = AB02
| ChEBI = 6754
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 607
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 57-42-1
| PubChem = 4058
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00454
| ChemSpiderID_Ref = 
| ChemSpiderID = 3918
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 9E338QE28F
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D08343
| C = 15
| H = 21
| N = 1
| O = 2
| smiles = CCOC(=O)C1(c2ccccc2)CCN(C)CC1
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C15H21NO2/c1-3-18-14(17)15(9-11-16(2)12-10-15)13-7-5-4-6-8-13/h4-8H,3,9-12H2,1-2H3
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = XADCESSVHJOZHK-UHFFFAOYSA-N
}}

'''Pethidine''', also known as '''meperidine''' and sold under the brand name '''Demerol''' among others, is a fully synthetic [[opioid]] [[analgesic|pain medication]] of the [[phenylpiperidine]] class.<ref>{{cite web|title=Demerol, Pethidine (meperidine) dosing, indications, interactions, adverse effects, and more|work=Medscape Reference|publisher=WebMD|access-date=9 April 2014|url=http://reference.medscape.com/drug/demerol-meperidine-343315#showall}}</ref><ref name="NZ">{{cite journal | vauthors = Shipton E | title = Should New Zealand continue signing up to the Pethidine Protocol? | journal = The New Zealand Medical Journal | volume = 119 | issue = 1230 | pages = U1875 | date = March 2006 | pmid = 16532042 | url = http://journal.nzma.org.nz/journal/119-1230/1875/content.pdf | url-status = dead | archive-url = https://web.archive.org/web/20140408211938/http://journal.nzma.org.nz/journal/119-1230/1875/content.pdf | archive-date = 2014-04-08 }}</ref><ref name="crit">{{cite journal | vauthors = Latta KS, Ginsberg B, Barkin RL | title = Meperidine: a critical review | journal = American Journal of Therapeutics | volume = 9 | issue = 1 | pages = 53–68 | date = January–February 2002 | pmid = 11782820 | doi = 10.1097/00045391-200201000-00010 | s2cid = 23410891 }}</ref><ref name="SHPA">{{cite journal |title=Strategy to Eliminate Pethidine Use in Hospitals |journal=Journal of Pharmacy Practice and Research |volume=38 |issue=2 |year=2008 |pages=88–89 |vauthors=MacPherson RD, Duguid MD |doi=10.1002/j.2055-2335.2008.tb00807.x |s2cid=71812645 |doi-access=free }}</ref><ref>{{cite journal | vauthors = Mather LE, Meffin PJ | title = Clinical pharmacokinetics of pethidine | journal = Clinical Pharmacokinetics | volume = 3 | issue = 5 | pages = 352–368 | date = September–October 1978 | pmid = 359212 | doi = 10.2165/00003088-197803050-00002 | s2cid = 35402662 }}</ref><ref name = AMH/> Synthesized in 1938<ref>US 2167351 Piperidine compounds and a process of preparing them</ref> as a potential [[anticholinergic]] agent by the German chemist Otto Eisleb, its analgesic properties were first recognized by Otto Schaumann while working for [[IG Farben]], in Germany.<ref name="Michaelis">{{cite journal | vauthors = Michaelis M, Schölkens B, Rudolphi K | title = An anthology from Naunyn-Schmiedeberg's archives of pharmacology | journal = Naunyn-Schmiedeberg's Archives of Pharmacology | volume = 375 | issue = 2 | pages = 81–84 | date = April 2007 | pmid = 17310263 | doi = 10.1007/s00210-007-0136-z | s2cid = 27774155 }}</ref> Pethidine is the prototype of a large family of analgesics including the pethidine 4-phenylpiperidines (e.g., [[piminodine]], [[anileridine]]), the prodines (e.g., [[alphaprodine]], [[MPPP]]), bemidones (e.g., [[ketobemidone]]), and others more distant, including [[diphenoxylate]] and analogues.<ref name="Allied Drugs 1957, pp 273-319">{{cite book | title = Morphine and Allied Drugs | vauthors = Reynolds AK, Randall LO | publisher =  University of Toronto Press/Oxford University Press | location = Toronto/London | date = 1957 | pages = 273–319 }}</ref>

Pethidine is indicated for the treatment of moderate to severe pain, and is delivered as a [[hydrochloride]] salt in tablets, as a syrup, or by [[intramuscular]], [[Subcutaneous injection|subcutaneous]], or [[intravenous injection]]. For much of the 20th century, pethidine was the opioid of choice for many physicians; in 1975, 60% of doctors prescribed it for acute pain and 22% for chronic severe pain.<ref name="Kaiko">{{cite journal | vauthors = Kaiko RF, Foley KM, Grabinski PY, Heidrich G, Rogers AG, Inturrisi CE, Reidenberg MM | title = Central nervous system excitatory effects of meperidine in cancer patients | journal = Annals of Neurology | volume = 13 | issue = 2 | pages = 180–185 | date = February 1983 | pmid = 6187275 | doi = 10.1002/ana.410130213 | s2cid = 44353966 }}</ref>

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It was patented in 1937 and approved for medical use in 1943.<ref name=Fis2006>{{cite book | vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=9783527607495 |page=52X |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA52X |language=en}}</ref> Compared with [[morphine]], pethidine was considered to be safer, carry a lower risk of addiction, and to be superior in treating the pain associated with [[Gallstone|biliary spasm]] or [[renal colic]] due to its assumed [[anticholinergic]] effects.<ref name = crit/> These were later discovered to be inaccurate assumptions, as it carries an equal risk of addiction, possesses no advantageous effects on biliary spasm or renal colic compared to other opioids. Due to the [[neurotoxicity]] of its metabolite, [[norpethidine]], it is more toxic than other opioids—especially during long-term use.<ref name = crit/> The norpethidine metabolite was found to have [[Serotonin|serotonergic]] effects, so pethidine could, unlike most opioids, increase the risk of triggering [[serotonin syndrome]].<ref name = crit/><ref name = SHPA/>