Volume : 12, Issue : 11, November – 2025
Title:
A REVIEW OF ORGANOPHOSPHATE POISONING AND THE ROLE OF PHARMACOLOGICAL ANTIDOTES
Authors :
Nihal Ashish Tamboli*, Suyash Shivaji Suryavanshi, Shrutika Amar Patil, Abhay Ganesh Potghan, Om Ajit Wangade, Diksha Vishal Auti
Abstract :
Organophosphate (OP) compounds are widely utilized in agriculture, industry, and chemical warfare, making OP poisoning a major global health concern, particularly in developing regions. These compounds exert their toxic effects by irreversibly inhibiting acetylcholinesterase (AChE), resulting in excessive accumulation of acetylcholine at synapses and overstimulation of muscarinic, nicotinic, and central nervous system (CNS) receptors. The ensuing cholinergic crisis can lead to respiratory failure, convulsions, and death if not managed promptly. Diagnosis is primarily clinical, supported by biochemical assays of plasma and red blood cell cholinesterase activity.
Management requires an integrated approach involving rapid decontamination, supportive care, and timely pharmacological intervention. The cornerstone of therapy includes atropine, which counters muscarinic hyperactivity; oximes such as pralidoxime and obidoxime, which reactivate inhibited AChE; and benzodiazepines for seizure control and neuroprotection. However, conventional antidotes face limitations such as poor blood–brain barrier penetration and reduced efficacy after enzyme “aging.” Recent advances have introduced bioscavenger enzymes, centrally acting oximes, and neuroprotective adjuncts like galantamine and magnesium sulfate, offering promising avenues for more effective management.
This review comprehensively discusses the chemistry, toxicodynamics, clinical features, diagnostic approaches, and therapeutic strategies of OP poisoning, with an emphasis on the pharmacological mechanisms, comparative efficacy, and recent innovations in antidotal therapy. The evolving landscape of enzyme-based and combination treatments underscores the need for continued research to overcome existing therapeutic challenges and improve patient survival outcomes.
Keywords: Organophosphate poisoning; Acetylcholinesterase inhibition; Atropine; Oximes; Pralidoxime; Obidoxime; HI-6; Benzodiazepines; Bioscavengers; Enzyme reactivation; Cholinergic crisis; Neuroprotection; Antidotal therapy.
Cite This Article:
Please cite this article in press Nihal Ashish Tamboli et al., A Review Of Organophosphate Poisoning And The Role Of Pharmacological Antidotes, Indo Am. J. P. Sci, 2025; 12(11).
REFERENCES:
1. Eddleston M, Buckley NA, Eyer P, Dawson AH. Management of acute organophosphorus pesticide poisoning. Lancet. 2008;371(9612):597–607.
2. Karalliedde L, Senanayake N. Organophosphorus insecticide poisoning. Br J Anaesth. 1989;63(6):736–750.
3. Peter JV, Moran JL, Graham PL. Oxime therapy and outcomes in human organophosphate poisoning: an evaluation using meta-analytic techniques. Crit Care Med. 2006;34(2):502–510.
4. Lotti M. Clinical toxicology of anticholinesterase agents in humans. In: Krieger RI, editor. Hayes’ Handbook of Pesticide Toxicology. 3rd ed. San Diego: Academic Press; 2010. p. 1543–1589.
5. Namba T, Nolte CT, Jackrel J, Grob D. Poisoning due to organophosphate insecticides: acute and chronic manifestations. Am J Med. 1971;50(4):475–492.
6. World Health Organization (WHO). Organophosphorus Pesticides: A General Introduction. Geneva: WHO; 1986.
7. Eyer P. The role of oximes in the management of organophosphorus pesticide poisoning. Toxicol Rev. 2003;22(3):165–190.
8. Taylor P. Anticholinesterase agents. In: Brunton LL, Hilal-Dandan R, Knollmann BC, editors. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 14th ed. New York: McGraw-Hill; 2023. p. 149–168.
9. John S, Kale M, Rathore N, Bhatnagar D. Protective effect of vitamin E in dimethoate and malathion induced oxidative stress in rat erythrocytes. J Nutr Biochem. 2001;12(9):500–504.
10. Eddleston M, Street JM, Self I, et al. A role for monitoring acetylcholinesterase inhibition in patients with organophosphorus insecticide poisoning. Toxicol Rev. 2010;29(2):83–93.
11. Jokanović M. Medical treatment of acute poisoning with organophosphorus and carbamate pesticides. Toxicol Lett. 2009;190(2):107–115.
12. Newmark J. Therapy for nerve agent poisoning. Arch Neurol. 2004;61(5):649–652.
13. Shih TM, Duniho SM, McDonough JH Jr. Control of nerve agent-induced seizures is critical for neuroprotection and survival. Toxicol Appl Pharmacol. 2003;188(2):69–80.
14. Kassa J. Review of oximes in the antidotal treatment of poisoning by organophosphorus nerve agents. J Toxicol Clin Toxicol. 2002;40(6):803–816.
15. Marrs TC. Organophosphate poisoning. Pharmacol Ther. 1993;58(1):51–66.
16. Vale JA, Lotti M, Scott GW. Organophosphorus and carbamate insecticides. In: Dart RC, editor. Medical Toxicology. 4th ed. Philadelphia: Lippincott Williams & Wilkins; 2015. p. 1465–1483.
17. Bajgar J. Organophosphates/nerve agent poisoning: mechanism of action, diagnosis, prophylaxis, and treatment. Adv Clin Chem. 2004;38:151–216.
18. Masson P, Lockridge O. Butyrylcholinesterase for protection from organophosphorus poisons: catalytic complexities and hysteretic behavior. Arch Biochem Biophys. 2010;494(2):107–120.
19. Doctor BP, Saxena A. Bioscavengers for the protection of humans against organophosphate toxicity. Chem Biol Interact. 2005;157–158:167–171.
20. Maxwell DM, Koplovitz I, Worek F, Sweeney RE. The in vivo efficacy of combinations of oximes against organophosphorus compound poisoning in guinea pigs. Toxicol Appl Pharmacol. 2008;230(3):319–328.
21. Singh AK, Jaiswal DK, Tiwari R, Prakash O. Organophosphorus poisoning and management strategies: A review. J Pharm Sci Res. 2018;10(2):282–289.
22. Liu J, Liu C, Liu M, Zhang W, Qiao Y. Advances in bioscavenger therapy for organophosphate poisoning. Front Pharmacol. 2020;11:573601.
23. Bhattacharyya K, Phaujdar S, Sarkar R, Mullick OS. Serum creatine phosphokinase: a probable marker of severity in organophosphorus poisoning. Toxicol Int. 2011;18(2):117–123.
24. Eddleston M, Dawson A, Karalliedde L. Early management after self-poisoning with an organophosphorus or carbamate pesticide – a treatment protocol for junior doctors. Crit Care. 2004;8(6):R391–R397.
25. Abdollahi M, Karami-Mohajeri S. A comprehensive review on experimental and clinical findings in intermediate syndrome following organophosphate poisoning. Toxicol Appl Pharmacol. 2012;258(3):309–314.
26. Roberts DM, Aaron CK. Managing acute organophosphorus pesticide poisoning. BMJ. 2007;334(7594):629–634.
27. Eyer F, Meischner V, Kiderlen D, Thiermann H, Worek F, Eyer P. Human poisoning with organophosphorus insecticides and nerve agents: mechanism of action and pharmacological management. Crit Rev Toxicol. 2008;38(10):759–789.
28. Singh S, Sharma N. Neurological syndromes following organophosphate poisoning. Neurol India. 2000;48(4):308–313.
29. 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.
30. Thiermann H, Worek F, Kehe K. Limitations and challenges in treatment of acute chemical warfare agent poisoning. Toxicology. 2013;314(3):167–175.
31. Balali-Mood M, Balali-Mood B. Neurotoxic disorders of organophosphorus compounds and their managements. Arch Iran Med. 2008;11(1):65–89.
32. Jeyaratnam J. Acute pesticide poisoning: a major global health problem. World Health Stat Q. 1990;43(3):139–144.
33. Kousba AA, Poet TS, Timchalk C. Influence of chemical structure on the inhibition of acetylcholinesterase by organophosphorus compounds. Toxicol Sci. 2003;71(2):390–400.
34. Jokanović M, Prostran M. Pyridinium oximes as cholinesterase reactivators. Structure–activity relationship and efficacy in the treatment of poisoning with organophosphorus compounds. Curr Med Chem. 2009;16(17):2177–2188.
35. Thompson CM, Richardson RJ. Anticholinesterase insecticides. In: Krieger R, editor. Handbook of Pesticide Toxicology. 3rd ed. San Diego: Academic Press; 2010. p. 1503–1525.
36. Worek F, Thiermann H, Wille T. Oxime treatment for nerve agent poisoning. Chem Biol Interact. 2016;259(Pt B):176–182.
37. Calesnick B, Christensen HD. Clinical toxicology of anticholinesterase agents. Clin Pharmacol Ther. 1977;22(4):488–495.
38. De Silva HJ, Wijewickrema R, Senanayake N. Does pralidoxime affect outcome of management in acute organophosphorus poisoning? Lancet. 1992;339(8794):1136–1138.
39. Bajgar J, Fusek J, Kassa J. Current strategies for the treatment of organophosphate poisoning. Clin Toxicol (Phila). 2008;46(6):489–511.
40. Gupta RC. Handbook of Toxicology of Chemical Warfare Agents. 3rd ed. London: Academic Press; 2020.
41. Karami-Mohajeri S, Abdollahi M. Toxic influence of organophosphate, carbamate, and organochlorine pesticides on cellular metabolism of lipids, proteins, and carbohydrates: a systematic review. Hum Exp Toxicol. 2011;30(9):1119–1140.
42. Raveendran R, Devi K, Gopalan TR, Anandaraj R. Evaluation of N-acetylcysteine as an adjuvant therapy in organophosphorus poisoning. Indian J Crit Care Med. 2015;19(9):531–536.
43. Chambers JE, Levi PE. Organophosphates: chemistry, fate, and effects. Toxicol Ind Health. 1992;8(1–2):1–11.
44. Bajgar J, Bartosova L, Fusek J. Prophylaxis against nerve agent poisoning. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2007;151(1):3–12.
45. Eddleston M, Gunnell D, Karunaratne A, de Silva D, Sheriff MH, Buckley NA. Epidemiology of intentional self-poisoning in rural Sri Lanka. Br J Psychiatry. 2005;187:583–584.
46. Jokanović M. Medical treatment of acute poisoning with organophosphorus and carbamate pesticides. Toxicol Lett. 2009;190(2):107–115.
47. Newmark J. Therapy for nerve agent poisoning. Arch Neurol. 2004;61(5):649–652.
48. Shih TM, Duniho SM, McDonough JH Jr. Control of nerve agent-induced seizures is critical for neuroprotection and survival. Toxicol Appl Pharmacol. 2003;188(2):69–80.
49. Kassa J. Review of oximes in the antidotal treatment of poisoning by organophosphorus nerve agents. J Toxicol Clin Toxicol. 2002;40(6):803–816.
50. Marrs TC. Organophosphate poisoning. Pharmacol Ther. 1993;58(1):51–66.
51. Vale JA, Lotti M, Scott GW. Organophosphorus and carbamate insecticides. In: Dart RC, editor. Medical Toxicology. 4th ed. Philadelphia: Lippincott Williams & Wilkins; 2015. p. 1465–1483.
52. Bajgar J. Organophosphates/nerve agent poisoning: mechanism of action, diagnosis, prophylaxis, and treatment. Adv Clin Chem. 2004;38:151–216.
53. Masson P, Lockridge O. Butyrylcholinesterase for protection from organophosphorus poisons: catalytic complexities and hysteretic behavior. Arch Biochem Biophys. 2010;494(2):107–120.
54. Doctor BP, Saxena A. Bioscavengers for the protection of humans against organophosphate toxicity. Chem Biol Interact. 2005;157–158:167–171.
55. Maxwell DM, Koplovitz I, Worek F, Sweeney RE. The in vivo efficacy of combinations of oximes against organophosphorus compound poisoning in guinea pigs. Toxicol Appl Pharmacol. 2008;230(3):319–328.
56. Karami-Mohajeri S, Abdollahi M. Toxic influence of organophosphate, carbamate, and organochlorine pesticides on cellular metabolism of lipids, proteins, and carbohydrates: a systematic review. Hum Exp Toxicol. 2011;30(9):1119–1140.
57. Raveendran R, Devi K, Gopalan TR, Anandaraj R. Evaluation of N-acetylcysteine as an adjuvant therapy in organophosphorus poisoning. Indian J Crit Care Med. 2015;19(9):531–536.
58. Chambers JE, Levi PE. Organophosphates: chemistry, fate, and effects. Toxicol Ind Health. 1992;8(1–2):1–11.