Antidotes for poisoning by alcohols that form toxic metabolites.

Kenneth McMartin, Dag Jacobsen, Knut Erik Hovda
Author Information
  1. Kenneth McMartin: Department of Pharmacology, Toxicology & Neuroscience, Louisiana State University Health Sciences Center - Shreveport, 1501 Kings Highway, Shreveport, Louisiana, 71130-3932, USA.
  2. Dag Jacobsen: Department of Acute Medicine, Division of Medicine, Oslo University Hospital, NO-0424, Oslo, Norway.
  3. Knut Erik Hovda: The Norwegian CBRNe Centre of Medicine, Department of Acute Medicine, Division of Medicine, Oslo University Hospital, NO-0424, Oslo, Norway.

Abstract

The alcohols, methanol, ethylene glycol and diethylene glycol, have many features in common, the most important of which is the fact that the compounds themselves are relatively non-toxic but are metabolized, initially by alcohol dehydrogenase, to various toxic intermediates. These compounds are readily available worldwide in commercial products as well as in homemade alcoholic beverages, both of which lead to most of the poisoning cases, from either unintentional or intentional ingestion. Although relatively infrequent in overall occurrence, poisonings by metabolically-toxic alcohols do unfortunately occur in outbreaks and can result in severe morbidity and mortality. These poisonings have traditionally been treated with ethanol since it competes for the active site of alcohol dehydrogenase and decreases the formation of toxic metabolites. Although ethanol can be effective in these poisonings, there are substantial practical problems with its use and so fomepizole, a potent competitive inhibitor of alcohol dehydrogenase, was developed for a hopefully better treatment for metabolically-toxic alcohol poisonings. Fomepizole has few side effects and is easy to use in practice and it may obviate the need for haemodialysis in some, but not all, patients. Hence, fomepizole has largely replaced ethanol as the toxic alcohol antidote in many countries. Nevertheless, ethanol remains an important alternative because access to fomepizole can be limited, the cost may appear excessive, or the physician may prefer ethanol due to experience.

Keywords

References

  1. Eur J Clin Pharmacol. 1989;37(6):599-604 [PMID: 2693117]
  2. Clin Toxicol (Phila). 2009 Jul;47(6):525-35 [PMID: 19586352]
  3. Clin Toxicol (Phila). 2015;53(7):589-95 [PMID: 26114345]
  4. Intensive Care Med. 2001 Aug;27(8):1370-8 [PMID: 11511951]
  5. Biochem Med. 1975 Aug;13(4):319-33 [PMID: 2163]
  6. Eur J Clin Pharmacol. 1995;49(3):211-3 [PMID: 8665997]
  7. Ann Emerg Med. 2009 Apr;53(4):439-450.e10 [PMID: 18639955]
  8. Am J Med. 1978 May;64(5):749-58 [PMID: 645740]
  9. Diabetes. 1974 May;23(5):433-9 [PMID: 4830177]
  10. BMC Clin Pharmacol. 2009 Mar 27;9:5 [PMID: 19327138]
  11. Clin Toxicol (Phila). 2011 Jul;49(6):478-84 [PMID: 21824058]
  12. Ann Intern Med. 1990 Oct 15;113(8):580-2 [PMID: 2400167]
  13. Tidsskr Nor Laegeforen. 2002 Oct 20;122(25):2444-6 [PMID: 12448112]
  14. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2015 Dec;159(4):666-76 [PMID: 25732977]
  15. Scand J Clin Lab Invest. 1983 Sep;43(5):377-9 [PMID: 6648324]
  16. Clin Toxicol (Phila). 2005;43(3):155-9 [PMID: 15902788]
  17. Clin Toxicol (Phila). 2008 Mar;46(3):181-6 [PMID: 18344099]
  18. Ann Intern Med. 1983 Apr;98(4):481-2 [PMID: 6838071]
  19. J Public Health (Oxf). 2015 Jun;37(2):354-9 [PMID: 24944254]
  20. Clin Toxicol (Phila). 2009 Nov;47(9):859-69 [PMID: 19852621]
  21. Clin Toxicol (Phila). 2007;45(2):152-7 [PMID: 17364632]
  22. Toxicol Sci. 2011 Nov;124(1):35-44 [PMID: 21856646]
  23. Am J Kidney Dis. 1997 Oct;30(4):568-70 [PMID: 9328374]
  24. Lancet. 1999 Sep 4;354(9181):831 [PMID: 10485727]
  25. Hum Exp Toxicol. 1996 Jun;15(6):494-6 [PMID: 8793532]
  26. Med Sci Law. 1978 Oct;18(4):231-7 [PMID: 703561]
  27. Clin Toxicol (Phila). 2005;43(4):221-7 [PMID: 16035197]
  28. Intensive Care Med. 2004 Sep;30(9):1842-6 [PMID: 15241587]
  29. N Engl J Med. 2009 May 21;360(21):2216-23 [PMID: 19458366]
  30. Medicine (Baltimore). 1981 Sep;60(5):373-82 [PMID: 7278621]
  31. Nephrol Dial Transplant. 1999 Jul;14(7):1774-7 [PMID: 10435895]
  32. J Toxicol Clin Toxicol. 2004;42(3):255-9 [PMID: 15362591]
  33. Clin Toxicol (Phila). 2012 Nov;50(9):823-31 [PMID: 22992104]
  34. Artif Organs. 1999 Feb;23(2):208-9 [PMID: 10027893]
  35. Clin Toxicol (Phila). 2015 Nov;53(9):884-92 [PMID: 26364866]
  36. J Emerg Med. 2014 Mar;46(3):e69-74 [PMID: 24199725]
  37. Ann Emerg Med. 2014 Jul;64(1):38-47 [PMID: 24439712]
  38. Hum Exp Toxicol. 1994 Feb;13(2):131-4 [PMID: 7908810]
  39. Acta Med Scand. 1982;212(1-2):5-10 [PMID: 7124461]
  40. J Anal Toxicol. 2005 Sep;29(6):586-8 [PMID: 16168185]
  41. J Toxicol Clin Toxicol. 2003;41(2):155-61 [PMID: 12733853]
  42. Vet Hum Toxicol. 2003 Feb;45(1):28-30 [PMID: 12583693]
  43. J Toxicol Clin Toxicol. 1992;30(4):565-74 [PMID: 1433427]
  44. J Toxicol Clin Toxicol. 1991;29(2):231-40 [PMID: 2051510]
  45. Clin Nephrol. 2005 Sep;64(3):190-7 [PMID: 16175943]
  46. Kidney Int. 2014 Jul;86(1):199-207 [PMID: 24621917]
  47. Intensive Care Med. 2005 Feb;31(2):189-95 [PMID: 15627163]
  48. Arch Biochem Biophys. 1980 Feb;199(2):606-14 [PMID: 6767446]
  49. Am J Med. 1979 Nov;67(5):804-7 [PMID: 507092]
  50. Clin Toxicol (Phila). 2007 Jun-Aug;45(5):516-21 [PMID: 17503258]
  51. JAMA. 1998 Apr 15;279(15):1175-80 [PMID: 9555756]
  52. Ann Emerg Med. 1995 Aug;26(2):202-7 [PMID: 7618784]
  53. N Engl J Med. 1999 Mar 18;340(11):832-8 [PMID: 10080845]
  54. Clin Toxicol (Phila). 2014 Dec;52(10):1032-283 [PMID: 25559822]
  55. J Toxicol Clin Toxicol. 2003;41(1):23-8 [PMID: 12645964]
  56. Clin Toxicol (Phila). 2010 Jun;48(5):401-6 [PMID: 20586570]
  57. Crit Care Med. 2015 Feb;43(2):461-72 [PMID: 25493973]
  58. Drug Metab Dispos. 1977 Mar-Apr;5(2):149-56 [PMID: 15807]
  59. Toxicol Lett. 1987 Feb;35(2-3):307-14 [PMID: 3824418]
  60. Clin Pharmacokinet. 2011 Apr;50(4):245-51 [PMID: 21271747]
  61. J Intern Med. 2005 Aug;258(2):181-90 [PMID: 16018795]
  62. Scand J Clin Lab Invest. 2015 Nov;75(7):610-4 [PMID: 26203958]
  63. J Toxicol Clin Toxicol. 2002;40(4):415-46 [PMID: 12216995]
  64. Am J Emerg Med. 1988 Sep;6(5):479-515 [PMID: 3415745]
  65. Clin Nephrol. 1997 Jul;48(1):52-3 [PMID: 9247780]
  66. N Engl J Med. 2001 Feb 8;344(6):424-9 [PMID: 11172179]
  67. Eur J Emerg Med. 2002 Sep;9(3):278-9 [PMID: 12394629]
  68. Mol Pharmacol. 1968 Sep;4(5):471-83 [PMID: 4972128]
  69. Pediatrics. 2001 Oct;108(4):E77 [PMID: 11581485]
  70. Ann Emerg Med. 2009 Apr;53(4):451-3 [PMID: 18986732]
  71. Lancet. 1970 Oct 10;2(7676):736-40 [PMID: 4195976]
  72. West J Med. 1985 Mar;142(3):337-40 [PMID: 3993008]
  73. Enzymol Biol Clin (Basel). 1966;6(4):297-304 [PMID: 4288711]
  74. Clin Toxicol (Phila). 2012 Sep;50(8):743-8 [PMID: 22891985]
  75. Hum Exp Toxicol. 2008 Jul;27(7):539-46 [PMID: 18829729]
  76. Bull World Health Organ. 2008 Oct;86(10):749-56 [PMID: 18949211]
  77. Clin Toxicol (Phila). 2014 Dec;52(10):1013-24 [PMID: 25345388]
  78. Vet Hum Toxicol. 1997 Feb;39(1):26-8 [PMID: 9004463]
  79. J Toxicol Clin Toxicol. 1993;31(1):81-93 [PMID: 8433417]
  80. J Toxicol Clin Toxicol. 1999;37(5):537-60 [PMID: 10497633]
  81. Clin Toxicol (Phila). 2015;53(8):797-806 [PMID: 26109326]
  82. JAMA Intern Med. 2014 Jun;174(6):912-7 [PMID: 24819553]
  83. Toxicol Lett. 2010 Feb 15;192(3):365-72 [PMID: 19931368]
  84. Toxicol Appl Pharmacol. 1978 Jul;45(1):201-8 [PMID: 99844]
  85. Br J Clin Pharmacol. 2016 Mar;81(3):505-15 [PMID: 26551875]
  86. Acta Chem Scand. 1969;23(3):892-902 [PMID: 4308830]
  87. Neurology. 2002 Nov 12;59(9):1460-3 [PMID: 12427908]
  88. Acta Med Scand. 1984;216(4):409-16 [PMID: 6516909]
  89. N Engl J Med. 1981 Jan 1;304(1):21-3 [PMID: 7432434]
  90. Acta Med Scand. 1982;212(1-2):11-5 [PMID: 7124456]
  91. Toxicol Sci. 2010 Sep;117(1):25-35 [PMID: 20530232]
  92. J Toxicol Clin Toxicol. 1997;35(2):187-91 [PMID: 9120889]
  93. Toxicol Sci. 2011 Oct;123(2):374-83 [PMID: 21804082]
  94. J Clin Pharmacol. 2009 Feb;49(2):130-7 [PMID: 19004845]
  95. Emerg Med Int. 2013;2013:638057 [PMID: 23431453]
  96. Surg Forum. 1970;21:32-3 [PMID: 5514911]
  97. Clin Toxicol (Phila). 2012 Jun;50(5):375-83 [PMID: 22554311]
  98. Toxicol Eur Res. 1978;1(5):2890-94 [PMID: 45188]
  99. J Med Toxicol. 2010 Jun;6(2):131-4 [PMID: 20422336]
  100. Am J Kidney Dis. 2000 May;35(5):958-62 [PMID: 10793034]
  101. J Public Health Policy. 2009 Jul;30(2):127-43 [PMID: 19597445]
  102. J Assoc Physicians India. 1968 Oct;16(10):801-5 [PMID: 5715506]

MeSH Term

Acidosis
Antidotes
Ethanol
Ethylene Glycol
Ethylene Glycols
Fomepizole
Humans
Methanol
Pyrazoles

Chemicals

Antidotes
Ethylene Glycols
Pyrazoles
Ethanol
diethylene glycol
Fomepizole
Ethylene Glycol
Methanol

Word Cloud

Created with Highcharts 10.0.0ethanolalcoholglycoltoxicpoisoningsfomepizolealcoholsdehydrogenasecanmaymethanolethylenediethylenemanyimportantcompoundsrelativelypoisoningAlthoughmetabolically-toxicmetabolitesusefeaturescommonfactnon-toxicmetabolizedinitiallyvariousintermediatesreadilyavailableworldwidecommercialproductswellhomemadealcoholicbeveragesleadcaseseitherunintentionalintentionalingestioninfrequentoveralloccurrenceunfortunatelyoccuroutbreaksresultseveremorbiditymortalitytraditionallytreatedsincecompetesactivesitedecreasesformationeffectivesubstantialpracticalproblemspotentcompetitiveinhibitordevelopedhopefullybettertreatmentFomepizolesideeffectseasypracticeobviateneedhaemodialysispatientsHencelargelyreplacedantidotecountriesNeverthelessremainsalternativeaccesslimitedcostappearexcessivephysicianpreferdueexperienceAntidotesform

Similar Articles

Cited By