Norpropoxyphene is a major metabolite of the opioidanalgesic drug dextropropoxyphene,[1] and is responsible for many of the side effects associated with use of this drug, especially the unusual toxicity seen during dextropropoxyphene overdose.[2][3][4] It has weaker analgesic effects than dextropropoxyphene itself, but is a relatively potent pro-convulsant and blocker of sodium and potassiumchannels,[5] particularly in heart tissue,[6][7] which produces prolonged intracardiac conduction time and can lead to heart failure following even relatively minor overdoses.[8][9][10][11] The toxicity of this metabolite makes dextropropoxyphene up to 10 times more likely to cause death following overdose compared to other similar mild opioid analgesics,[12] and has led to dextropropoxyphene being withdrawn from the market in some countries.[13]
Because norpropoxyphene has a long half-life in the body of up to 36 hours (compared to around 6–12 hours for dextropropoxyphene), it can accumulate in tissues during chronic use of dextropropoxyphene-containing medications, especially in people whose excretion of drugs is slower than normal such as young children, the elderly, and individuals with reduced kidney or liver function, and so side effects including serious adverse events are more common in these groups and use of dextropropoxyphene should be avoided where possible.[14][15][16]
Referencesedit
^Somogyi AA, Menelaou A, Fullston SV (October 2004). "CYP3A4 mediates dextropropoxyphene N-demethylation to nordextropropoxyphene: human in vitro and in vivo studies and lack of CYP2D6 involvement". Xenobiotica; the Fate of Foreign Compounds in Biological Systems. 34 (10): 875–87. doi:10.1080/00498250400008371. PMID 15764408. S2CID 7680532.
^Gustafson A, Gustafsson B (1976). "Acute poisoning with dextropropoxyphene. Clinical symptoms and plasma concentrations". Acta Medica Scandinavica. 200 (4): 241–8. doi:10.1111/j.0954-6820.1976.tb08226.x. PMID 983792.
^McBay AJ (August 1976). "Propoxyphene and norpropoxyphene concentrations in blood and tissues in cases of fatal overdose". Clinical Chemistry. 22 (8): 1319–21. doi:10.1093/clinchem/22.8.1319. PMID 949842.
^Nickander RC, Emmerson JL, Hynes MD, Steinberg MI, Sullivan HR (August 1984). "Pharmacologic and toxic effects in animals of dextropropoxyphene and its major metabolite norpropoxyphene: a review". Human Toxicology. 3 Suppl: 13S–36S. doi:10.1177/096032718400300103. PMID 6090306. S2CID 1333582.
^Nickander R, Smits SE, Steinberg MI (January 1977). "Propoxyphene and norpropoxyphene: pharmacologic and toxic effects in animals". The Journal of Pharmacology and Experimental Therapeutics. 200 (1): 245–53. PMID 13200.
^Lund-Jacobsen H (March 1978). "Cardio-respiratory toxicity of propoxyphene and norpropoxyphene in conscious rabbits". Acta Pharmacologica et Toxicologica. 42 (3): 171–8. doi:10.1111/j.1600-0773.1978.tb02187.x. PMID 580345.
^Ulens C, Daenens P, Tytgat J (December 1999). "Norpropoxyphene-induced cardiotoxicity is associated with changes in ion-selectivity and gating of HERG currents". Cardiovascular Research. 44 (3): 568–78. doi:10.1016/s0008-6363(99)00258-8. PMID 10690289.
^Simkin S, Hawton K, Sutton L, Gunnell D, Bennewith O, Kapur N (March 2005). "Co-proxamol and suicide: preventing the continuing toll of overdose deaths". QJM. 98 (3): 159–70. doi:10.1093/qjmed/hci026. PMID 15728397.
^Afshari R, Good AM, Maxwell SR, Bateman DN (October 2005). "Co-proxamol overdose is associated with a 10-fold excess mortality compared with other paracetamol combination analgesics". British Journal of Clinical Pharmacology. 60 (4): 444–7. doi:10.1111/j.1365-2125.2005.02468.x. PMC1884826. PMID 16187978.
^Sandilands EA, Bateman DN (August 2008). "Co-proxamol withdrawal has reduced suicide from drugs in Scotland". British Journal of Clinical Pharmacology. 66 (2): 290–3. doi:10.1111/j.1365-2125.2008.03206.x. PMC2492929. PMID 18489609.
^Gibson TP, Giacomini KM, Briggs WA, Whitman W, Levy G (May 1980). "Propoxyphene and norpropoxyphene plasma concentrations in the anephric patient". Clinical Pharmacology and Therapeutics. 27 (5): 665–70. doi:10.1038/clpt.1980.94. PMID 7371364. S2CID 24099122.
^Inturrisi CE, Colburn WA, Verebey K, Dayton HE, Woody GE, O'Brien CP (February 1982). "Propoxyphene and norpropoxyphene kinetics after single and repeated doses of propoxyphene". Clinical Pharmacology and Therapeutics. 31 (2): 157–67. doi:10.1038/clpt.1982.25. PMID 7056023. S2CID 38421623.
^Flanagan RJ, Johnston A, White AS, Crome P (October 1989). "Pharmacokinetics of dextropropoxyphene and nordextropropoxyphene in young and elderly volunteers after single and multiple dextropropoxyphene dosage". British Journal of Clinical Pharmacology. 28 (4): 463–9. doi:10.1111/j.1365-2125.1989.tb03527.x. PMC1379997. PMID 2590604.
February 13, 2024
norpropoxyphene, major, metabolite, opioid, analgesic, drug, dextropropoxyphene, responsible, many, side, effects, associated, with, this, drug, especially, unusual, toxicity, seen, during, dextropropoxyphene, overdose, weaker, analgesic, effects, than, dextro. Norpropoxyphene is a major metabolite of the opioid analgesic drug dextropropoxyphene 1 and is responsible for many of the side effects associated with use of this drug especially the unusual toxicity seen during dextropropoxyphene overdose 2 3 4 It has weaker analgesic effects than dextropropoxyphene itself but is a relatively potent pro convulsant and blocker of sodium and potassium channels 5 particularly in heart tissue 6 7 which produces prolonged intracardiac conduction time and can lead to heart failure following even relatively minor overdoses 8 9 10 11 The toxicity of this metabolite makes dextropropoxyphene up to 10 times more likely to cause death following overdose compared to other similar mild opioid analgesics 12 and has led to dextropropoxyphene being withdrawn from the market in some countries 13 Norpropoxyphene NamesPreferred IUPAC name 2S 3R 3 Methyl 4 methylamino 1 2 diphenylbutan 2 yl propanoateIdentifiersCAS Number 32501 12 5 Y3D model JSmol Interactive imageChemSpider 2341605 YPubChem CID 3084563UNII C812VVS96K YInChI InChI 1S C21H27NO2 c1 4 20 23 24 21 17 2 16 22 3 19 13 9 6 10 14 19 15 18 11 7 5 8 12 18 h5 14 17 22H 4 15 16H2 1 3H3 t17 21 m1 s1 YKey IKACRWYHQXOSGM UTKZUKDTSA N YInChI 1 C21H27NO2 c1 4 20 23 24 21 17 2 16 22 3 19 13 9 6 10 14 19 15 18 11 7 5 8 12 18 h5 14 17 22H 4 15 16H2 1 3H3 t17 21 m1 s1Key IKACRWYHQXOSGM UTKZUKDTBFSMILES O C O C c1ccccc1 Cc2ccccc2 C H C CNC CCPropertiesChemical formula C 21H 27N O 2Molar mass 325 445Except where otherwise noted data are given for materials in their standard state at 25 C 77 F 100 kPa Y verify what is Y N Infobox references Because norpropoxyphene has a long half life in the body of up to 36 hours compared to around 6 12 hours for dextropropoxyphene it can accumulate in tissues during chronic use of dextropropoxyphene containing medications especially in people whose excretion of drugs is slower than normal such as young children the elderly and individuals with reduced kidney or liver function and so side effects including serious adverse events are more common in these groups and use of dextropropoxyphene should be avoided where possible 14 15 16 References edit Somogyi AA Menelaou A Fullston SV October 2004 CYP3A4 mediates dextropropoxyphene N demethylation to nordextropropoxyphene human in vitro and in vivo studies and lack of CYP2D6 involvement Xenobiotica the Fate of Foreign Compounds in Biological Systems 34 10 875 87 doi 10 1080 00498250400008371 PMID 15764408 S2CID 7680532 Gustafson A Gustafsson B 1976 Acute poisoning with dextropropoxyphene Clinical symptoms and plasma concentrations Acta Medica Scandinavica 200 4 241 8 doi 10 1111 j 0954 6820 1976 tb08226 x PMID 983792 McBay AJ August 1976 Propoxyphene and norpropoxyphene concentrations in blood and tissues in cases of fatal overdose Clinical Chemistry 22 8 1319 21 doi 10 1093 clinchem 22 8 1319 PMID 949842 Nickander RC Emmerson JL Hynes MD Steinberg MI Sullivan HR August 1984 Pharmacologic and toxic effects in animals of dextropropoxyphene and its major metabolite norpropoxyphene a review Human Toxicology 3 Suppl 13S 36S doi 10 1177 096032718400300103 PMID 6090306 S2CID 1333582 Nickander R Smits SE Steinberg MI January 1977 Propoxyphene and norpropoxyphene pharmacologic and toxic effects in animals The Journal of Pharmacology and Experimental Therapeutics 200 1 245 53 PMID 13200 Lund Jacobsen H March 1978 Cardio respiratory toxicity of propoxyphene and norpropoxyphene in conscious rabbits Acta Pharmacologica et Toxicologica 42 3 171 8 doi 10 1111 j 1600 0773 1978 tb02187 x PMID 580345 Ulens C Daenens P Tytgat J December 1999 Norpropoxyphene induced cardiotoxicity is associated with changes in ion selectivity and gating of HERG currents Cardiovascular Research 44 3 568 78 doi 10 1016 s0008 6363 99 00258 8 PMID 10690289 Young RJ July 1983 Dextropropoxyphene overdosage Pharmacological considerations and clinical management Drugs 26 1 70 9 doi 10 2165 00003495 198326010 00004 PMID 6349964 S2CID 46978533 Lawson AA Northridge DB 1987 Dextropropoxyphene overdose Epidemiology clinical presentation and management Medical Toxicology and Adverse Drug Experience 2 6 430 44 doi 10 1007 BF03259877 PMID 3323775 S2CID 13452948 Afshari R Maxwell S Dawson A Bateman DN 2005 ECG abnormalities in co proxamol paracetamol dextropropoxyphene poisoning Clinical Toxicology 43 4 255 9 doi 10 1081 CLT 66069 PMID 16035201 S2CID 36817890 Simkin S Hawton K Sutton L Gunnell D Bennewith O Kapur N March 2005 Co proxamol and suicide preventing the continuing toll of overdose deaths QJM 98 3 159 70 doi 10 1093 qjmed hci026 PMID 15728397 Afshari R Good AM Maxwell SR Bateman DN October 2005 Co proxamol overdose is associated with a 10 fold excess mortality compared with other paracetamol combination analgesics British Journal of Clinical Pharmacology 60 4 444 7 doi 10 1111 j 1365 2125 2005 02468 x PMC 1884826 PMID 16187978 Sandilands EA Bateman DN August 2008 Co proxamol withdrawal has reduced suicide from drugs in Scotland British Journal of Clinical Pharmacology 66 2 290 3 doi 10 1111 j 1365 2125 2008 03206 x PMC 2492929 PMID 18489609 Gibson TP Giacomini KM Briggs WA Whitman W Levy G May 1980 Propoxyphene and norpropoxyphene plasma concentrations in the anephric patient Clinical Pharmacology and Therapeutics 27 5 665 70 doi 10 1038 clpt 1980 94 PMID 7371364 S2CID 24099122 Inturrisi CE Colburn WA Verebey K Dayton HE Woody GE O Brien CP February 1982 Propoxyphene and norpropoxyphene kinetics after single and repeated doses of propoxyphene Clinical Pharmacology and Therapeutics 31 2 157 67 doi 10 1038 clpt 1982 25 PMID 7056023 S2CID 38421623 Flanagan RJ Johnston A White AS Crome P October 1989 Pharmacokinetics of dextropropoxyphene and nordextropropoxyphene in young and elderly volunteers after single and multiple dextropropoxyphene dosage British Journal of Clinical Pharmacology 28 4 463 9 doi 10 1111 j 1365 2125 1989 tb03527 x PMC 1379997 PMID 2590604 Retrieved from https en wikipedia org w index php title Norpropoxyphene amp oldid 1170395325, wikipedia, wiki, book, books, library,
