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VOLUME 23 , ISSUE S4 ( December, 2019 ) > List of Articles

INVITED ARTICLE

Antidotes in Poisoning

Keywords : Antidote, Binding, Poison, Toxin

Citation Information : Antidotes in Poisoning. Indian J Crit Care Med 2019; 23 (S4).

DOI: 10.5005/jp-journals-10071-23310

License: CC BY-NC 4.0

Published Online: 01-04-2015

Copyright Statement:  Copyright © 2019; The Author(s).


Abstract

Introduction: Antidotes are agents that negate the effect of a poison or toxin. Antidotes mediate its effect either by preventing the absorption of the toxin, by binding and neutralizing the poison, antagonizing its end-organ effect, or by inhibition of conversion of the toxin to more toxic metabolites. Antidote administration may not only result in the reduction of free or active toxin level, but also in the mitigation of end-organ effects of the toxin by mechanisms that include competitive inhibition, receptor blockade or direct antagonism of the toxin. Mechanism of action of antidotes: Reduction in free toxin level can be achieved by specific and non-specific agents that bind to the toxin. The most commonly used non-specific binding agent is activated charcoal. Specific binders include chelating agents, bioscavenger therapy and immunotherapy. In some situations, enhanced elimination can be achieved by urinary alkalization or hemadsorption. Competitive inhibition of enzymes (e.g. ethanol for methanol poisoning), enhancement of enzyme function (e.g. oximes for organophosphorus poisoning) and competitive receptor blockade (e.g. naloxone, flumazenil) are other mechanisms by which antidotes act. Drugs such as N-acetyl cysteine and sodium thiocyanate reduce the formation of toxic metabolites in paracetamol and cyanide poisoning respectively. Drugs such as atropine and magnesium are used to counteract the end-organ effects in organophosphorus poisoning. Vitamins such as vitamin K, folic acid and pyridoxine are used to antagonise the effects of warfarin, methotrexate and INH respectively in the setting of toxicity or overdose. This review provides an overview of the role of antidotes in poisoning.


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  1. Karami M, Estachri MRAE. Principles of toxicotherapy: general and specific therapy. Sch Acad J Pharm 2015;4(3):153–156.
  2. Wang RY, Kazzi ZN. Editorial: antidotes and rescue therapies. Curr Pharm Biotechnol 2012;13(10):1914–1916. DOI: 10.2174/138920112802273164.
  3. Jacobsen D. The relative efficacy of antidotes. J Toxicol Clin Toxicol 2008;33(6):705–708. DOI: 10.3109/15563659509010633.
  4. De Garbino JP, Haines JA, Jacobsen D, Meredith T. Evaluation of antidotes: activities of the International Programme on Chemical Safety. J Toxicol Clin Toxicol 2009;35(4):333–343. DOI: 10.3109/15563659709043364.
  5. Salyer SW. Toxicology emergencies. In: Salyer SW, ed. Essential Emergency Medicine, ch. 17 Philadelphia: W.B. Saunders; 2007. pp. 923–1049.
  6. Pichamuthu K, Jerobin J, Nair A, John G, Kamalesh J, Thomas K, et al. Bioscavenger therapy for organophosphate poisoning - an open-labeled pilot randomized trial comparing fresh frozen plasma or albumin with saline in acute organophosphate poisoning in humans. Clin Toxicol (Phila) 2010;48(8):813–819. DOI: 10.3109/15563650.2010.518970.
  7. Peter JV, Moran JL, Graham PL. Advances in the management of organophosphate poisoning. Expert Opin Pharmacother 2007;8(10):1451–1464. DOI: 10.1517/14656566.8.10.1451.
  8. Pillay VV. Current views on antidotal therapy in managing cases of poisoning and overdose. J Assoc Physicians India 2008;56:881–892.
  9. Chyka PA, Seger D, Krenzelok EP, Vale JA, American Academy of Clinical Toxicology, European Association of Poisons Centres and Clinical Toxicologists. Position paper: single-dose activated charcoal. Clin Toxicol (Phila) 2005;43(2):61–87. DOI: 10.1081/CLT-51867.
  10. Merigian KS, Blaho KE. Single-dose oral activated charcoal in the treatment of the self-poisoned patient: a prospective, randomized, controlled trial. Am J Ther 2002;9(4):301–308. DOI: 10.1097/00045391-200207000-00007.
  11. Eddleston M, Juszczak E, Buckley NA, Senarathna L, Mohamed F, Dissanayake W, et al. Multiple-dose activated charcoal in acute self-poisoning: a randomised controlled trial. Lancet 2008;371(9612): 579–587. DOI: 10.1016/S0140-6736(08)60270-6.
  12. Do SI, Park S, Ha H, Kim HJ. Fatal pulmonary complications associated with activated charcoal: an autopsy case. Basic Appl Pathol 2009;2(3):106–108. DOI: 10.1111/j.1755-9294.2009.01048.x.
  13. Goulbourne KB, Cisek JE. Small-bowel obstruction secondary to activated charcoal and adhesions. Ann Emerg Med 1994;24(1): 108–110. DOI: 10.1016/S0196-0644(94)70170-9.
  14. Brent J, Jaeger A, McGuigan M, Meulenbelt J, Tenenbein M, Bradberry S, et al. Position statement and practice guidelines on the use of multi-dose activated charcoal in the treatment of acute poisoning. J Toxicol Clin Toxicol 1999;37(6):731–751. DOI: 10.1081/CLT-100102451.
  15. Weinberg GL, VadeBoncouer T, Ramaraju GA, Garcia-Amaro MF, Cwik MJ. Pretreatment or resuscitation with a lipid infusion shifts the dose-response to bupivacaine-induced asystole in rats. Anesthesiology 1998;88(4):1071–1075. DOI: 10.1097/00000542-199804000-00028.
  16. Ozcan MS, Weinberg G. Intravenous lipid emulsion for the treatment of drug toxicity. J Intensive Care Med 2012;29(2):59–70. DOI: 10.1177/0885066612445978.
  17. Rothschild L, Bern S, Oswald S, Weinberg G. Intravenous lipid emulsion in clinical toxicology. Scand J Trauma Resusc Emerg Med 2010;18:51. DOI: 10.1186/1757-7241-18-51.
  18. Gil H-W, Kim S-J, Yang J-O, Lee E-Y, Hong S-Y. Clinical outcome of hemoperfusion in poisoned patients. Blood Purif 2010;30(2):84–88. DOI: 10.1159/000318585.
  19. Proudfoot AT, Krenzelok EP, Vale JA. Position paper on urine alkalinization. J Toxicol Clin Toxicol 2004;42(1):1–26. DOI: 10.1081/CLT-120028740.
  20. Barceloux DG, Bond GR, Krenzelok EP, Cooper H, Vale JA, American Academy of Clinical Toxicology Ad Hoc Committee on the Treatment Guidelines for Methanol Poisoning. American Academy of Clinical Toxicology practice guidelines on the treatment of methanol poisoning. J Toxicol Clin Toxicol 2002;40(4):415–446. DOI: 10.1081/CLT-120006745.
  21. Miller H, Barceloux DG, Krenzelok EP, Olson K, Watson W. American Academy of Clinical Toxicology practice guidelines on the treatment of ethylene glycol poisoning. J Toxicol Clin Toxicol 2015;37(5):537–560. DOI: 10.1081/CLT-100102445.
  22. Eddleston M, Eyer P, Worek F, Juszczak E, Alder N, Mohamed F, et al. Pralidoxime in acute organophosphorus insecticide poisoning--a randomised controlled trial. PLoS Med 2009;6(6):e1000104. DOI: 10.1371/journal.pmed.1000104.
  23. Peter JV, Moran JL, Graham P. Oxime therapy and outcomes in human organophosphate poisoning: an evaluation using meta-analytic techniques. Crit Care Med 2006;34(2):502–510. DOI: 10.1097/01.CCM.0000198325.46538.AD.
  24. Hoffman EJ, Warren EW. Flumazenil: a benzodiazepine antagonist. Clin Pharm 1993;12(9):641–656; quiz 699–701.
  25. Kreshak AA, Cantrell FL, Clark RF, Tomaszewski CA. A poison center's ten-year experience with flumazenil administration to acutely poisoned adults. J Emerg Med 2012;43(4):677–682. DOI: 10.1016/j.jemermed.2012.01.059.
  26. Weinbroum AA, Flaishon R, Sorkine P, Szold O, Rudick V. A risk-benefit assessment of flumazenil in the management of benzodiazepine overdose. Drug Saf 1997;17(3):181–196. DOI: 10.2165/00002018-199717030-00004.
  27. Weinbroum A, Rudick V, Sorkine P, Nevo Y, Halpern P, Geller E, et al. Use of flumazenil in the treatment of drug overdose. Crit Care Med 1996;24(2):199–206. DOI: 10.1097/00003246-199602000- 00004.
  28. Rzasa Lynn R, Galinkin JL. Naloxone dosage for opioid reversal: current evidence and clinical implications. Ther Adv Drug Saf 2018;9(1):63–88. DOI: 10.1177/2042098617744161.
  29. Lavonas EJ, Drennan IR, Gabrielli A, Heffner AC, Hoyte CO, Orkin AM, et al. Part 10: special circumstances of resuscitation: 2015 American Heart Association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation 2015;132(18 Suppl 2):S501–S518. DOI: 10.1161/CIR.0000000000000264.
  30. Piperno E, Mosher AH, Berssenbruegge DA, Winkler JD, Smith RB. Pathophysiology of acetaminophen overdosage toxicity: implications for management. Pediatrics 1978;62(5 Pt 2 Suppl):880–889.
  31. Rumack BH, Peterson RC, Koch GG, Amara IA. Acetaminophen overdose. 662 cases with evaluation of oral acetylcysteine treatment. Arch Intern Med 1981;141(3 Spec No):380–385. DOI: 10.1001/archinte.1981.00340030112020.
  32. Prescott LF, Ballantyne A, Proudfoot AT, Park J, Adriaenssens P. Treatment of paracetamol (acetaminophen) poisoning with N-acetylcysteine. Lancet 1977;310(8035):432–434. DOI: 10.1016/S0140-6736(77)90612-2.
  33. Curry SC, Carlton MW, Raschke RA. Prevention of fetal and maternal cyanide toxicity from nitroprusside with coinfusion of sodium thiosulfate in gravid ewes. Anesth Analg 1997;84(5):1121–1126. DOI: 10.1213/00000539-199705000-00031.
  34. Lheureux P, Penaloza A, Gris M. Pyridoxine in clinical toxicology: a review. Eur J Emerg Med 2005;12(2):78–85. DOI: 10.1097/00063110-200504000-00007.
  35. Howard SC, McCormick J, Pui C-H, Buddington RK, Harvey RD. Preventing and managing toxicities of high-dose methotrexate. Oncologist 2016;21(12):1471–1482. DOI: 10.1634/theoncologist.2015-0164.
  36. Buckley NA, Dawson AH, Juurlink DN, Isbister GK. Who gets antidotes? choosing the chosen few. Br J Clin Pharmacol 2016;81(3):402–407. DOI: 10.1111/bcp.12894.
  37. Cooper GM, Le Couteur DG, Richardson D, Buckley NA. A randomized clinical trial of activated charcoal for the routine management of oral drug overdose. QJM 2005;98(9):655–660. DOI: 10.1093/qjmed/hci102.
  38. Pawar KS, Bhoite RR, Pillay CP, Chavan SC, Malshikare DS, Garad SG. Continuous pralidoxime infusion versus repeated bolus injection to treat organophosphorus pesticide poisoning: a randomised controlled trial. Lancet 2006;368(9553):2136–2141. DOI: 10.1016/S0140-6736(06)69862-0.
  39. Johnson S, Peter JV, Thomas K, Jeyaseelan L, Cherian AM. Evaluation of two treatment regimens of pralidoxime (1 g single bolus dose vs 12 g infusion) in the management of organophosphorus poisoning. J Assoc Physicians India 1996;44(8):529–531.
  40. Kosnett MJ. The role of chelation in the treatment of arsenic and mercury poisoning. J Med Toxicol 2013;9(4):347–354. DOI: 10.1007/s13181-013-0344-5.
  41. Chan BSH, Buckley NA. Digoxin-specific antibody fragments in the treatment of digoxin toxicity. Clin Toxicol 2014;52(8):824–836. DOI: 10.3109/15563650.2014.943907.
  42. Ghannoum M, Bouchard J, Nolin TD, Ouellet G, Roberts DM. Hemoperfusion for the treatment of poisoning: technology, determinants of poison clearance, and application in clinical practice. Semin Dial 2014;27(4):350–361. DOI: 10.1111/sdi.12246.
  43. Borron SW, Baud FJ. Antidotes for acute cyanide poisoning. Curr Pharm Biotechnol 2012;13(10):1940–1948. DOI: 10.2174/138920112802273182.
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