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Dextropropoxyphene Overdosage

Pharmacological Considerations and Clinical Management

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Summary

Dextropropoxyphene is a widely prescribed synthetic opiate-like drug of uncertain analgesic efficacy which, in acute overdosage, manifests all the features of opiate toxicity. It is rapidly absorbed and, in association with other central nervous system depressants such as alcohol or benzodiazepine drugs, may be rapidly fatal.

Seriously overdosed patients are comatose with respiratory depression, vomiting, seizures and circulatory collapse; small pupils are a useful diagnostic marker. The first priority is to establish the airway and treat convulsions, if present. All the features of overdosage are then rapidly and safely reversed by the specific opiate antagonist naloxone given intravenously. High tissue concentrations and slow elimination of dextropropoxyphene metabolites make continued and intensive monitoring after resuscitation essential because sudden unpredictable deterioration may occur for up to 24 hours. Other more slowly toxic co-ingestants such as paracetamol (acetaminophen) are often present and should be detected and treated as necessary.

Dextropropoxyphene poisoning is now probably one of the most common causes of self-poisoning death because, although there is an effective antidote, subjects frequently succumb before treatment can be made available.

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References

  • Abernethy, D.R.; Greenblatt, D.J.; Steel, K. and Shader, R.I.: Impairment of hepatic drug oxidation by propoxyphene. Annals of Internal Medicine 97: 223–224 (1982).

    PubMed  CAS  Google Scholar 

  • Amsterdam, E.A.; Rendig, S.V.; Henderson, G.L. and Mason, D.P.: Depression of myocardial contractile function by propoxyphene and norpropoxyphene. Journal of Cardiovascular Pharmacology 3: 129–138 (1981).

    Article  PubMed  CAS  Google Scholar 

  • Barclay, W.R.: Propoxyphene. Journal of the American Medical Association 241: 1689 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Barraclough, C.J. and Lowe, R.A.: Failure of naloxone to reverse the cardiotoxicity of Distalgesic overdose. Postgraduate Medical Journal 58: 667–668 (1982).

    Article  PubMed  CAS  Google Scholar 

  • Baselt, R.C.; Wright, J.A.; Turner, J.A. and Cravey, R.H.: Propoxyphene and norproxyphene tissue concentrations in fatalities associated with propoxyphene hydrochloride and propoxyphene napsylate. Archives of Toxicology 34: 145–149 (1975).

    Article  PubMed  CAS  Google Scholar 

  • Beattie, J.O.; Chen, P. and MacDonald, T.H.: Neonatal Distalgesic poisoning. (Correspondence.) Lancet 2: 49 (1981).

    Article  PubMed  CAS  Google Scholar 

  • Beaver, W.T.: Mild analgesics. II. A review of their clinical pharmacology. American Journal of Medical Science 251: 576–599 (1966).

    Article  CAS  Google Scholar 

  • Bogartz, L.J. and Miller, W.C: Pulmonary oedema associated with propoxyphene intoxication. Journal of the American Medical Association 215: 259–261 (1971).

    Article  PubMed  CAS  Google Scholar 

  • Bradberry, J.C. and Raebel, M.A.: Continuous infusion of naloxone in the treatment of narcotic overdose. Drug Intelligence and Clinical Pharmacy 15: 945–950 (1981).

    PubMed  CAS  Google Scholar 

  • Cann, H.M. and Verhulst, H.L.: Convulsions as a manifestation of acute dextropropoxyphene intoxication. American Journal of Diseases of Children 99: 380–381 (1960).

    CAS  Google Scholar 

  • Carson, D.J.L. and Carson, E.D.: Fatal dextropropoxyphene poisoning in Northern Ireland. Lancet 1: 894–897 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Christensen, H.: Dodelige forgisteninger med dekstropropoksifen. Ugeskrift for Laeger 137: 2571–2576 (1975).

    PubMed  CAS  Google Scholar 

  • Claghorn, J. and Schooler, J.C: Propoxyphene hydrochloride: A drug of abuse. Journal of the American Medical Association 196: 1089–1091 (1966).

    Article  PubMed  CAS  Google Scholar 

  • Critchley, J.; Illingworth, R.N.; Pottage, A.; Proudfoot, A.T. and Prescott, L.: Acute poisoning with Distalgesic. British Medical Journal 1: 342 (1979).

    Article  Google Scholar 

  • Data Sheet Compendium, The Association of the British Pharmaceutical Industry, pp. 272–274, 548–550 (Datapharm, London 1981).

  • Editorial: Dangers of dextropropoxyphene. British Medical Journal 1: 668 (1977).

  • Editorial: Treatment of dextropropoxyphene poisoning. Lancet 2: 542 (1977).

  • Elmes, P.C.: The contribution of prescribed drugs to the incidence of accidental and deliberate poisoning in the community. Acta Pharmacologica et Toxicologica 41 (Suppl.): 517–521 (1977).

    PubMed  Google Scholar 

  • Elson, A. and Domino, E.F.: Dextropropoxyphene addiction: Observation of a case. Journal of the American Medical Association 183: 482–485 (1963).

    Google Scholar 

  • Emmerson, J.L.; Gibson, W.R. and Anderson, R.C.: Acute toxicity of propoxyphene salts. Toxicology and Applied Pharmacology 19: 445–451 (1971).

    Article  PubMed  CAS  Google Scholar 

  • Evans, L.E.J.; Roscoe, P.; Swainson, C.P. and Prescott, L.F.: Treatment of drug overdosage with naloxone a specific narcotic antagonist. Lancet 1: 452–455 (1973).

    Article  PubMed  CAS  Google Scholar 

  • Evans, J.M.; Hogg, I.J.; Lunn, J.N. and Rosen, M.: Degree and duration of reversal by naloxone of effects of morphine in conscious subjects. British Medical Journal 2: 589–591 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Food and Drugs Administration, Department of Health, Education and Welfare: Propoxyphene. Federal Regulations 44: 11837 (1979).

    Google Scholar 

  • Ford, M.J.; Kellet, R.J.; Busuttil, A. and Finlayson, N.D.C.: Dextropropoxyphene and jaundice. British Medical Journal 2: 674 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Gary, N.E.; Maher, J.F. and DeMyttenaere, M.H.: Acute propoxyphene hydrochloride intoxication. Archives of Internal Medicine 121: 453–454 (1968).

    Article  PubMed  CAS  Google Scholar 

  • Giacomini, K.M.; Giacomini, J.C; Gibson, T.P. and Levy, G.: Propoxyphene and norpropoxyphene plasma concentrations after oral propoxyphene in cirrhotic patients with and without surgically constructed portacaval shunt. Clinical Pharmacology and Therapeutics 28: 417–424 (1980a).

    Article  PubMed  CAS  Google Scholar 

  • Giacomini, K.M.; Gibson, T.P. and Levy, G.: Effect of haemodialysis on propoxyphene and norpropoxyphene concentrations in blood of anephric patients. Clinical Pharmacology and Therapeutics 27: 508–514 (1980b).

    Article  PubMed  CAS  Google Scholar 

  • Gibson, T.P. and Nelson, H.A.: Drug kinetics and artificial kidneys. Clinical Pharmacokinetics 2: 403–426 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Gibson, T.P.; Giacomini, K.M.; Briggs, W.A.; Whitman, W. and Levy, G.: Propoxyphene and norpropoxyphene plasma concentrations in the anephric patient. Clinical Pharmacology and Therapeutics 27: 665–670 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Giertsen, J.C. and Dibb, W.L.: Dodelige forgiftninger med dextropropoksyfen. Tidsskrift for Praktisk Laegegering 100: 283–285 (1980).

    CAS  Google Scholar 

  • Gourlay, G.K. and Coulthard, K.: The role of naloxone infusions in the treatment of overdoses of long half-life narcotic agonists: Application to nor-methadone. British Journal of Clinical Pharmacology 15: 269–272 (1983).

    Article  PubMed  CAS  Google Scholar 

  • Gram, L.F.; Show, J.; Way, W.L.; Heltberg, J. and Bodin, N.O.: d-Propoxyphene kinetics after single oral and intravenous doses in man. Clin. Pharm. Ther. 26: 473–482 (1979).

    CAS  Google Scholar 

  • Gwilt, P.R. and Perrier, D.: Plasma protein binding and distribution characteristics of drugs as indices of their haemodialyzability. Clinical Pharmacology and Therapeutics 24: 154–161 (1978).

    PubMed  CAS  Google Scholar 

  • Harris, B. and Harper, M.: Psychosis after dextropropoxyphene. Lancet 2: 743 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Holland, D.R. and Steinberg, M.I.: Electrophysiologic properties of propoxyphene and norpropoxyphene in canine cardiac conducting tissues in vitro and in vivo. Toxicology and Applied Pharmacology 47: 123–133 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Holding, T.A.; Buglass, D.; Duffy, J.C. and Kreitman, N.: Parasuicide in Edinburgh —a seven year review 1968–74. British Journal of Psychiatry 130: 534–543 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Hunt, V.: Treatment of dextropropoxyphene poisoning. British Medical Journal 1: 554 (1973).

    Article  PubMed  CAS  Google Scholar 

  • Inturrisi, CE.; Colburn, W.A.; Vereby, K.; Dayton, H.E.; Woody, G.E. and O’Brien, C.P. Propoxyphene and norpropoxyphene kinetics after single and repeated doses of propoxyphene. Clinical Pharmacology and Therapeutics 31: 157–167 (1982).

    Article  PubMed  CAS  Google Scholar 

  • Jones, R.V.: Warfarin and Distalgesic interaction. British Medical Journal 1: 460 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Kane Jr, F.J. and Norton, J.L.: Addiction to propoxyphene. Journal of the American Medical Association 211: 300 (1970).

    Article  PubMed  Google Scholar 

  • Kersh, E.S.: Treatment of dextropropoxyphene overdosage with naloxone. Chest 63: 112–114 (1973).

    Article  PubMed  CAS  Google Scholar 

  • Kiplinger, G.F. and Nickander, R.: Pharmacologic basis for use of propoxyphene. Journal of the American Medical Association 216: 289–292 (1971).

    Article  PubMed  CAS  Google Scholar 

  • Lasagna, L.: Clinical evaluation of morphine and its substitutes as analgesics. Pharmacological Reviews 16: 47–63 (1964).

    PubMed  CAS  Google Scholar 

  • Lawson, A.A.H. and McCallum, C.J.: Trends in acute poisoning in a district general hospital. Health Bulletin 37: 121–127 (1979).

    PubMed  CAS  Google Scholar 

  • Lovejoy, F.H.; Mitchell, A.A. and Goldman, P.: The management of propoxyphene poisoning. Journal of Paediatrics 85: 98–100 (1974).

    Article  Google Scholar 

  • Lund, A. and Nielsen, G.D.: Dextropropoxyphene concentrations in blood in cases of fatal poisoning. Zeitschrift Für Rechtsmedizin 71: 148–150 (1972).

    Article  CAS  Google Scholar 

  • Lund-Jacobsen, H.: Cardio-respiratory toxicity of propoxyphene and norpropoxyphene in conscious rabbits. Acta Pharmacologica et Toxicologica 42: 171–178 (1978).

    Article  PubMed  CAS  Google Scholar 

  • McBay, A.J.: Propoxyphene and norpropoxyphene concentrations in blood and tissues in cases of fatal overdose. Clinical Chemistry 22: 1319–1321 (1976).

    PubMed  CAS  Google Scholar 

  • McBay, A.J.; Turk, R.F.; Corbett, B.W. and Hudson, P.: Determination of propoxyphene in biological materials. Journal of Forensic Science 19: 81 (1974).

    CAS  Google Scholar 

  • McCarthy, W.H. and Keenan, R.L.: Propoxyphene hydrochloride poisoning: Report of the first fatality. Journal of the American Medical Association 187: 460–461 (1964).

    Article  PubMed  CAS  Google Scholar 

  • McMahon, R.E.; Rodolfo, A.S. and Culp, R.W.: The fate of radiocarbon labelled propoxyphene in rat, dog and human. Toxicology and Applied Pharmacology 19: 427–444 (1971).

    Article  PubMed  CAS  Google Scholar 

  • Matthew, H. and Lawson, A.A.H.: Treatment of common acute poisonings, 4th edition (Churchill Livingstone,Edinburgh, London, New York 1979).

  • Messick, R.T.: Evaluation of acetaminophen, propoxyphene and their combination in office practice. Journal of Clinical Pharmacology 19: 227–230 (1979).

    PubMed  CAS  Google Scholar 

  • Miller, R.R.; Feingold, A. and Paxinos, J.: Propoxyphene hydrochloride —a critical review. Journal of the American Medical Association 213: 996–1006 (1970).

    Article  PubMed  CAS  Google Scholar 

  • Mitchell, A.A.; Lovejoy, F.H. and Goldman, P.: Drug ingestions associated with miosis in comatose children. Journal of Pediatrics 89: 303–305 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Monforte, J.R. and Spitz, W.U.: Drug deaths involving propoxyphene —An assessment in metropolitan Detroit. Preventive Medicine 5: 573–575 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Moore, R.A. and Rumack, B.H.: Naloxone underdosage after narcotic poisoning. American Journal of Diseases of Children 134: 156–158 (1980).

    PubMed  CAS  Google Scholar 

  • Musa, M.N. and Lyons, L.L.: Effect of food and liquid on the pharmacokinetics of propoxyphene. Current Therapeutic Research 19: 669–674 (1976).

    PubMed  CAS  Google Scholar 

  • Neill, A. and Terenius, L.: d-Propoxyphene acts differently from morphine on opioid receptor-effector mechanisms. European Journal of Pharmacology 69: 33–39 (1981).

    Article  Google Scholar 

  • Nickander, R.; Smits, S.E. and Steinberg, M.I.: Propoxyphene and norpropoxyphene: Pharmacologic and toxic effects in animals. Journal of Pharmacology and Experimental Therapeutics 200: 245–253 (1977).

    PubMed  CAS  Google Scholar 

  • Oguma, T. and Levy, G.: Acute effect of ethanol on hepatic first pass elimination of propoxyphene in rats. Journal of Pharmacology and Experimental Therapeutics 219: 7–13 (1981).

    PubMed  CAS  Google Scholar 

  • Orme, M.; Breckenbridge, A. and Cook, P.: Warfarin and Distalgesic interaction. British Medical Journal 1: 200 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Owen, N.L.: Abuse of propoxyphene. Journal of the American Medical Association 216: 2016 (1971).

    Article  PubMed  CAS  Google Scholar 

  • Pohland, A. and Sullivan, H.R.: Analgesics: Esters of 4-dialhylamino-1,2-diphenyl-2-butanols. Journal of the American Chemical Association 75: 4458–4461 (1953).

    CAS  Google Scholar 

  • Poust, R.I. and Jaffe, J.N.: Propoxyphene bioavailability monograph. Journal of the American Pharmacological Association 2: 97–101 (1976).

    Google Scholar 

  • Prescott, L.F.: Paracetamol overdosage: Pharmacological considerations and clinical management. Drugs 25: 290–314 (1983).

    Article  PubMed  CAS  Google Scholar 

  • Prescott, L.F.; Park, J.; Ballantyne, A.; Adriaensseus, P. and Proudfoot, A.T.: Treatment of paracetamol (acetaminophen) poisoning with N-acetylcysteine. Lancet 2: 432–434 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Quillian, W.W. and Dunn, C.A.: Neonatal drug withdrawal from propoxyphene. Journal of the American Medical Association 235: 2128–2129 (1976).

    Article  PubMed  Google Scholar 

  • Robbins, E.B.: Pharmacologic effects of new analgesics alpha-4-dimethylamino-2-d-phenyl-3-methyl-4-propionyl oxybutane. Journal of the American Pharmacological Association 44: 497–499 (1955).

    Article  CAS  Google Scholar 

  • Shenfield, G.M.; Jones, A.N. and Paterson, J.W.: Effect of restrictions on prescribing patterns for dextropropoxyphene. British Medical Journal 281: 651–653 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Simonsen, J.: Accidental fatal drug poisoning with particular reference to dextropropoxyphene. Forensic Science 10: 127–132 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Starkey, I.R. and Lawson, A.A.H.: Acute poisoning with Distalgesic. British Medical Journal 2: 1468 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Sturner, W.Q. and Garriott, J.C.: Deaths involving propoxyphene. A study of 41 cases over a two year period. Journal of the American Medical Association 223: 1125–1130 (1973).

    Article  PubMed  CAS  Google Scholar 

  • Sundvist, L. and Petrovics, J.: Fatal poisoning with dextropropoxyphene containing analgesics —suicide or not? Acta Medica Scandinavica 196: 467–472 (1974).

    Article  Google Scholar 

  • Tarala, R. and Forrest, J.A.H.: Treatment of dextropropoxyphene poisoning. British Medical Journal 2: 550 (1973).

    Article  PubMed  CAS  Google Scholar 

  • Tennant, F.S.: Complications of propoxyphene abuse. Archives of Internal Medicine 132: 191–194 (1973).

    Article  PubMed  Google Scholar 

  • The National Poisons Information Service Monitoring Group: Analgesic poisoning: A multi-centre, prospective study. Human Toxicology 1: 7–23 (1981).

    Article  Google Scholar 

  • Therapeutic category report on National Prescription Audit (Gosselin and Company, Dedham, Massachusetts, 18 December 1969).

  • Verebely, K. and Inturrisi, C.E.: The simultaneous determination of propoxyphene and norpropoxyphene in human biofluids using gas-liquid chromatography. Journal of Chromatography 75: 195–201 (1973).

    Article  PubMed  CAS  Google Scholar 

  • Verebely, K. and Inturrisi, C.E.: Disposition of propoxyphene and norpropoxyphene in man after a single oral dose. Clinical Pharmacology and Therapeutics 15: 302–309 (1974).

    PubMed  CAS  Google Scholar 

  • Voigt, J.: Norkomandodsfald. Ugeskrift for Laeger 132: 1955–1960 (1970).

    Google Scholar 

  • Volkans, G.N.: Self-poisoning and suicide due to paracetamol. Journal of Internal Medical Research 4 (Suppl. 4): 7–13 (1976).

    Google Scholar 

  • Wagner, J.C.: Welling, P.G.; Roth, S.B.; Sakamer, E.; Lee, D.P. and Walker, J.E.: Plasma concentrations of propoxyphene in man following oral administration of the drug in solution and capsule forms. International Journal of Clinical Pharmacology 5: 371–380 (1972).

    CAS  Google Scholar 

  • Waife, S.P.; Gruber, CM.; Rodda, B.E. and Nash, J.F.: Problems and solutions to single dose testing of analgesics —comparison of propoxyphene, codeine and fenoprofen. International Journal of Clinical Pharmacology 12: 301–304 (1975).

    CAS  Google Scholar 

  • Waife, S.P.; Gruber, CM; Rodda, B.E. and Nash, J.F.: Analgesia, plasma levels, and dosage of propoxyphene. International Journal of Clinical Pharmacology 13: 177–181 (1976).

    CAS  Google Scholar 

  • Wall, R.; Linford, S.M.J. and Akhter, M.: Addiction to Distalgesic (dextropropoxyphene). British Medical Journal 1: 1213–1214 (1980).

    Article  Google Scholar 

  • Way, E.L. and Adler, T.K.: The pharmacologic implications of the fate of morphine and its surrogates. Pharmacological Reviews 12: 383–396 (1960).

    PubMed  CAS  Google Scholar 

  • Welling, P.G.; Lyons, F.L.; Tse, F.L.S. and Craig, W.A.: Propoxyphene and norpropoxyphene. Influence of diet and fluid on plasma levels. Clinical Pharmacology and Therapeutics 19: 559–565 (1976).

    PubMed  CAS  Google Scholar 

  • Wetli, C.V. and Badnarczyk, L.R.: Deaths related to propoxyphene overdose: A ten year assessment. Southern Medical Journal 73: 1205–1209 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Whittington, R.M.: Dextropropoxyphene (Distalgesic) overdose in the West Midlands. British Medical Journal 2: 172–173 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Whittington, R.M.: Dextropropoxyphene addiction. Lancet 2: 743–744 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Wiseman, M.S.; Chapman, S.; Huldstock, G.E. and Loehry, C.A.: Dextropropoxyphene overdosage and naloxone. British Medical Journal 1: 1159 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Wolen, R.L.; Gruber, C.H.; Kiplinger, G.F. and Scholz, N.E.: Concentrations of propoxyphene in human plasma following oral, intramuscular and intravenous administration. Toxicology and Applied Pharmacology 19: 480–492 (1971a).

    Article  PubMed  CAS  Google Scholar 

  • Wolen, R.L.; Gruber, CM.; Kiplinger, G.F. and Scholz, N.E.: Concentrations of propoxyphene in human plasma following repeated oral doses. Toxicology and Applied Pharmacology 19: 493–497 (1971b).

    Article  PubMed  CAS  Google Scholar 

  • Wolen, R.L.; Ziege, E.A. and Gruber, CM.: Determination of propoxyphene and norpropoxyphene by chemical ionization mass fragmentography. Clinical Pharmacology and Therapeutics 17: 15–20 (1975).

    PubMed  CAS  Google Scholar 

  • Wolfe, R.C; Reidenberg, M. and Vispo, R.H.: Propoxyphene (Darvon) addiction and withdrawal syndrome. Annals of Internal Medicine 70: 773–776 (1969).

    PubMed  CAS  Google Scholar 

  • Young, DJ.: Propoxyphene suicides. Archives of Internal Medicine 129: 62–66 (1972).

    Article  PubMed  CAS  Google Scholar 

  • Young, R.J. and Lawson, A.A.H.: Distalgesic poisoning —cause for concern. British Medical Journal 1: 1045–1047 (1980).

    Article  Google Scholar 

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  1. Diabetic and Dietetic Department, The Royal Infirmary, Edinburgh, EH3 9YW, Scotland

    Robert J. Young

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Young, R.J. Dextropropoxyphene Overdosage. Drugs 26, 70–79 (1983). https://doi.org/10.2165/00003495-198326010-00004

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