Volume : 12, Issue : 11, November – 2025

Title:

ANTIDOTES IN CLINICAL TOXICOLOGY: PHARMACOLOGICAL APPROACHES TO POISON MANAGEMENT

Authors :

Prerana Prakash Lokare*, Dhanshree Baliram Gadhir, Radhika Shital Bodh, Prachiti Vasant Katkar, Sanika Samadhan Kumbhar, Shashikant Shivan and Langote

Abstract :

Poisoning remains a major global health challenge, with increasing morbidity and mortality associated with pharmaceutical agents, chemicals, industrial toxins, household poisons, and envenomation. Rapid identification and timely administration of an appropriate antidote are critical determinants of patient outcome. This review provides a comprehensive and structured evaluation of key antidotes used in modern clinical toxicology, emphasizing their mechanisms of action, pharmacological properties, dosing strategies, safety considerations, and clinical evidence supporting their use. Antidotes discussed include naloxone for opioid toxicity, N-acetylcysteine for acetaminophen poisoning, atropine–pralidoxime combinations for organophosphate exposure, flumazenil for benzodiazepine overdose, hydroxocobalamin for cyanide poisoning, fomepizole for toxic alcohol ingestion, digoxin-specific Fab fragments, vitamin K–PCC–FFP combinations for anticoagulant-associated bleeding, and therapies for cardiotoxic overdoses such as glucagon and high-dose insulin euglycemia treatment. Specialized antidotes for methemoglobinemia, heavy metal intoxication, envenomation, and emerging anticoagulants such as dabigatran and factor Xa inhibitors are also reviewed. Through an organized framework, this article highlights essential monitoring parameters, adverse effects, practical availability issues, and current guideline recommendations. This synthesis aims to support clinicians, pharmacists, and toxicology practitioners in delivering evidence-based, timely, and effective poison management.
Keywords: Antidotes; Clinical toxicology; Poison management; N-acetylcysteine; Naloxone; Organophosphate poisoning; Fomepizole; Cyanide antidotes; Digoxin toxicity; Antivenoms; Methylene blue; Chelation therapy; High-dose insulin euglycemia; Warfarin reversal; Idarucizumab; Andexanet alfa.

Cite This Article:

Please cite this article in press Prerana Prakash Lokare et al., Antidotes In Clinical Toxicology: Pharmacological Approaches To Poison Management, Indo Am. J. P. Sci, 2025; 12(11).

REFERENCES:

1. Hoffman RS, Howland MA, Lewin NA, Nelson LS, Goldfrank LR, editors. Goldfrank’s Toxicologic Emergencies. 11th ed. New York: McGraw-Hill; 2019.
2. Dart RC, editor. Medical Toxicology. 4th ed. Philadelphia: Lippincott Williams & Wilkins; 2015.
3. Olson KR. Poisoning and Drug Overdose. 8th ed. New York: McGraw-Hill; 2022.
4. Brent J. Fomepizole for ethylene glycol and methanol poisoning. N Engl J Med. 2009;360(21):2216–23.
5. Hoffman RJ, Nelson LS. Antidotes in depth. Emerg Med Clin North Am. 2015;33(1):1–21.
6. Bond GR. Naloxone for opioid toxicity. Clin Toxicol. 2020;58(7):525–31.
7. Boyer EW. Management of opioid analgesic overdose. N Engl J Med. 2012;367(2):146–55.
8. Bateman DN, Dear JW, Thomas SHL. Acetaminophen-induced hepatic injury: mechanism and NAC therapy. Br J Clin Pharmacol. 2014;78(2):201–11.
9. Heard KJ. Acetylcysteine for acetaminophen poisoning. N Engl J Med. 2008;359(3):285–92.
10. Chiew AL, Fountain JS, Graudins A, Isbister GK, Buckley NA. Summary of NAC dosing strategies. Clin Toxicol. 2018;56(11):873–82.
11. Eddleston M, Buckley NA, Eyer P, Dawson AH. Management of organophosphorus insecticide poisoning. Lancet. 2008;371(9612):597–607.
12. Peter JV, Moran JL, Graham PL. Oxime therapy for organophosphate poisoning. Crit Care Med. 2006;34(2):502–10.
13. Roberts DM, Aaron CK. Management of carbamate poisoning. Clin Toxicol. 2007;45(3):310–6.
14. Woolf AD, Erdman AR, Nelson LS. Atropine therapy in pesticide poisoning. Clin Toxicol. 2010;48(1):1–17.
15. Greenblatt DJ. Flumazenil safety profile. J Toxicol Clin Toxicol. 1993;31(3):307–19.
16. Penninga EI, Graudal N. Flumazenil in benzodiazepine overdose. Cochrane Database Syst Rev. 2016;8:CD004804.
17. Borron SW, Baud FJ, Megarbane B. Hydroxocobalamin for cyanide poisoning. Crit Care. 2006;10(5):R148.
18. Bebarta VS, Tanen DA, Lairet J. Cyanide poisoning treatment strategies. Ann Emerg Med. 2010;55(4):345–51.
19. Megarbane B. Antidotes for toxic alcohol poisoning. Toxicol Rev. 2005;24(2):77–80.
20. Barceloux DG, Bond GR. American Academy of Clinical Toxicology practice guidelines: methanol poisoning. J Toxicol Clin Toxicol. 2002;40(4):415–46.
21. Juurlink DN. Digoxin toxicity and treatment with Fab fragments. CMAJ. 2007;177(11):1277–9.
22. Chan BS, Buckley NA. Evidence-based review of digoxin Fab. Clin Toxicol. 2014;52(6):824–36.
23. Ageno W, Gallus AS, Wittkowsky A, Crowther M. Oral anticoagulant management and reversal. Chest. 2012;141(2 Suppl):e44S–88S.
24. Schulman S, Bijsterveld NR. Anticoagulant reversal. Semin Thromb Hemost. 2012;38(7):712–20.
25. Siegal DM, Curnutte JT. Idarucizumab for dabigatran reversal. N Engl J Med. 2015;373(6):511–20.
26. Connolly SJ, Milling TJ. Andexanet alfa for factor Xa inhibitor reversal. N Engl J Med. 2016;375(12):1131–41.
27. Page C, Bawazeer G. Methylene blue in methemoglobinemia. Clin Toxicol. 2019;57(4):247–53.
28. Wright RO, Lewander WJ, Woolf AD. Methemoglobinemia: clinical features and management. Ann Emerg Med. 1999;34(5):646–56.
29. Choudhry VP, Pati HP. G6PD deficiency and oxidant drugs. Indian J Pediatr. 2000;67(12):893–6.
30. Aaseth J, Crisponi G, Anderson O. Chelation Therapy in the Treatment of Metal Intoxication. Amsterdam: Elsevier; 2016.
31. Kosnett MJ. Lead poisoning and chelation therapy. N Engl J Med. 2007;357(26):2638–47.
32. Shannon M. Succimer in lead poisoning. Pediatrics. 1997;99(2):251–7.
33. Chisolm JJ. Chelation therapy using sodium EDTA. J Pediatr. 1968;72(1):1–7.
34. Anderson CP, Powers WT. Deferoxamine therapy in iron poisoning. J Pediatr. 1979;94(3):529–31.
35. Dart RC, McNally J. Iron poisoning: diagnosis and management. Pediatr Clin North Am. 2006;53(2):393–409.
36. Lavonas EJ, et al. High-dose insulin therapy for beta-blocker toxicity. Clin Toxicol. 2011;49(4):277–83.
37. Engebretsen KM, Kaczmarek KM, Morgan J. HIET for calcium channel blocker overdose. Ann Emerg Med. 2011;57(6):643–53.
38. Lheureux PE, Zahir S, Gris M. Glucagon in beta-blocker poisoning. Intensive Care Med. 2006;32(7):1049–55.
39. Levine M, et al. Lipid emulsion therapy for drug toxicity. Clin Toxicol. 2016;54(1):1–9.
40. Cave G, Harvey M. Lipid rescue in local anesthetic toxicity. Anaesthesia. 2009;64(2):122–4.
41. Jamaty C, Bailey B, Larocque A. Lipid emulsions for systemic toxicity of lipophilic drugs. J Pharm Pract. 2010;23(3):297–304.
42. Bush SP, Siedenburg E. Snake antivenoms: effectiveness and safety. Clin Toxicol. 2020;58(4):223–34.
43. Williams HF, Vaiyapuri S, Gutiérrez JM. Challenges in antivenom therapy. Toxins. 2019;11(10):564.
44. Isbister GK. Antivenom dosing and adverse reactions. Lancet. 2010;375(9729):1538–46.
45. Seifert SA, Boyer LV. North American snakebite treatment guidelines. Ann Emerg Med. 2001;37(3):304–14.
46. Banerji S, Anderson IB. Pyridoxine in isoniazid poisoning. Ann Emerg Med. 2001;38(6):640–5.
47. Sahin S, Kalkan M. Severe isoniazid toxicity and pyridoxine therapy. Clin Toxicol. 2016;54(5):453–7.
48. Burns MJ, Linden CH. Physostigmine for anticholinergic delirium. Ann Emerg Med. 2000;35(4):374–81.
49. Shannon M. Physostigmine safety review. Pediatrics. 1998;102(3):709–14.
50. Graudins A, Lee HM. Octreotide in sulfonylurea poisoning. Clin Toxicol. 2017;55(7):683–90.
51. Boyle PJ. Octreotide reversal of hypoglycemia. Diabetes Care. 1993;16(3):553–7.
52. Hoffman RS. Clinical utility of antidotes. Clin Pharmacol Ther. 2008;84(2):173–5.
53. Juurlink DN. Poisoning management: clinical decision-making. CMAJ. 2014;186(13):1015–9.
54. Farkas A. Emergency stabilization in toxicology. Crit Care Clin. 2019;35(2):203–22.
55. Wax PM. Historical development of antidotes. Clin Toxicol. 2013;51(3):175–9.
56. Whyte IM, Dawson AH, Buckley NA. Toxidrome recognition. Med J Aust. 2002;176(4):161–5.
57. Thanacoody HKR. Multiple-dose activated charcoal. Clin Toxicol. 2016;54(2):88–99.
58. Juurlink DN, Gosselin S. Extracorporeal removal in poisoning. Kidney Int. 2019;96(1):32–42.
59. Roberts DM, et al. Gastric decontamination guidelines. Clin Toxicol. 2013;51(3):130–7.
60. American College of Medical Toxicology (ACMT). Antidote stocking guidelines. J Med Toxicol. 2018;14(4):345–52.