Clinical Uses of Snake Antivenoms

  • Ponlapat Rojnuckarin
Living reference work entry


Antivenom is the key treatment for venomous snakebites. It is produced by purification of polyclonal IgG from plasma of large animals pre-immunized by snake venom. Polyvalent antivenoms, which neutralize venoms from many species prevalent in the areas of uses, are preferred over monovalent antivenoms because the snake species are frequently unidentifiable in clinical practice. Antivenom therapy can promptly reverse snakebite-induced coagulopathy and limb edema, but muscular paralysis from presynaptic toxins, tissue necrosis, and renal failure resolve much more slowly, especially when antivenoms are given late after bites. Effective treatments of these latter complications remain to be determined. The anaphylaxis-like early adverse reaction is the major limitation of antivenom uses. It is unpredictable by the immediate hypersensitivity skin test, and therefore, every antivenom administration requires close observation. Highly purified caprylic acid-stabilized IgG antivenoms show significantly lower rates of reactions. Clinical judgments to give antivenom should be individualized weighing potential benefits versus risks of antivenoms for the snakes in specific regions. Due to the high cost of antivenom production, this therapy is usually lacking in developing countries where snakebites are very common. Strategies for the adequate supply of good quality antivenoms are strongly needed.


Snake Venom Caprylic Acid Venom Component Antivenom Therapy Presynaptic Neurotoxin 
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  1. Archundia IG, de Roodt AR, Ramos-Cerrillo B, Chippaux JP, Olguín-Pérez L, Alagón A, Stock RP. Neutralization of Vipera and Macrovipera venoms by two experimental polyvalent antisera: a study of paraspecificity. Toxicon. 2011;57(7–8):1049–56.PubMedCrossRefGoogle Scholar
  2. Boyer LV, Seifert SA, Cain JS. Recurrence phenomena after immunoglobulin therapy for snake envenomations: part 2. Guidelines for clinical management with crotaline Fab antivenom. Ann Emerg Med. 2001;37(2):196–201.PubMedCrossRefGoogle Scholar
  3. Calvete JJ. Antivenomics and venom phenotyping: a marriage of convenience to address the performance and range of clinical use of antivenoms. Toxicon. 2010;56(7):1284–91.PubMedCrossRefGoogle Scholar
  4. Calvete JJ. Snake venomics: from the inventory of toxins to biology. Toxicon. 2013;75(Dec 1):44-62.Google Scholar
  5. Chotenimitkhun R, Rojnuckarin P. Systemic antivenom and skin necrosis after green pit viper bites. Clin Toxicol. 2008;46(2):122–5.CrossRefGoogle Scholar
  6. Chotwiwatthanakun C, Pratanaphon R, Akesowan S, Sriprapat S, Ratanabanangkoon K. Production of potent polyvalent antivenom against three elapid venoms using a low dose, low volume, multi-site immunization protocol. Toxicon. 2001;39(10):1487–94.PubMedCrossRefGoogle Scholar
  7. Cook DA, Samarasekara CL, Wagstaff SC, Kinne J, Wernery U, Harrison RA. Analysis of camelid IgG for antivenom development: immunoreactivity and preclinical neutralisation of venom-induced pathology by IgG subclasses, and the effect of heat treatment. Toxicon. 2010a;56(4):596–603.PubMedCrossRefGoogle Scholar
  8. Cook DA, Owen T, Wagstaff SC, Kinne J, Wernery U, Harrison RA. Analysis of camelid IgG for antivenom development: serological responses of venom-immunised camels to prepare either monospecific or polyspecific antivenoms for West Africa. Toxicon. 2010b;56(3):363–72.PubMedCrossRefGoogle Scholar
  9. de Andrade FG, Eto SF, Santos Ferraro AC N d, Gonzales Marioto DT, Vieira NJ, Cheirubim AP, de Paula Ramos S, Venâncio EJ. The production and characterization of anti-bothropic and anti-crotalic IgY antibodies in laying hens: a long term experiment. Toxicon. 2013;66:18–24.PubMedCrossRefGoogle Scholar
  10. de Silva HA, Pathmeswaran A, Ranasinha CD, Jayamanne S, Samarakoon SB, Hittharage A, Kalupahana R, Ratnatilaka GA, Uluwatthage W, Aronson JK, Armitage JM, Lalloo DG, de Silva HJ. Low-dose adrenaline, promethazine, and hydrocortisone in the prevention of acute adverse reactions to antivenom following snakebite: a randomised, double-blind, placebo-controlled trial. PLoS Med. 2011;8(5):e1000435.PubMedCentralPubMedCrossRefGoogle Scholar
  11. Durban J, Pérez A, Sanz L, Gómez A, Bonilla F, Rodríguez S, Chacón D, Sasa M, Angulo Y, Gutiérrez JM, Calvete JJ. Integrated “omics” profiling indicates that miRNAs are modulators of the ontogenetic venom composition shift in the Central American rattlesnake, Crotalus simus simus. BMC Genomics. 2013;14:234.PubMedCentralPubMedCrossRefGoogle Scholar
  12. Fan HW, Marcopito LF, Cardoso JL, França FO, Malaque CM, Ferrari RA, Theakston RD, Warrell DA. Sequential randomised and double blind trial of promethazine prophylaxis against early anaphylactic reactions to antivenom for bothrops snake bites. BMJ. 1999;318(7196):1451–2.PubMedCentralPubMedCrossRefGoogle Scholar
  13. Gawarammana IB, Kularatne SA, Dissanayake WP, Kumarasiri RP, Senanayake N, Ariyasena H. Parallel infusion of hydrocortisone +/− chlorpheniramine bolus injection to prevent acute adverse reactions to antivenom for snakebites. Med J Aust. 2004;180(1):20–3.PubMedGoogle Scholar
  14. Gold BS, Dart RC, Barish RA. Bites of venomous snakes. N Engl J Med. 2002;347(5):347–56.PubMedCrossRefGoogle Scholar
  15. Gutiérrez JM. Improving antivenom availability and accessibility: science, technology, and beyond. Toxicon. 2012;60(4):676–87.PubMedCrossRefGoogle Scholar
  16. Gutiérrez JM, León G, Rojas G, Lomonte B, Rucavado A, Chaves F. Neutralization of local tissue damage induced by Bothrops asper (terciopelo) snake venom. Toxicon. 1998;36(11):1529–38.PubMedCrossRefGoogle Scholar
  17. Gutiérrez JM, León G, Lomonte B. Pharmacokinetic-pharmacodynamic relationships of immunoglobulin therapy for envenomation. Clin Pharmacokinet. 2003;42(8):721–41.PubMedCrossRefGoogle Scholar
  18. Hanvivatvong O, Phanuphak P, Sakulramrung R. Kinetic study of cobra venom and effect of anti-cobra venom in rabbits. In: Pochanukul C, editor. Plant, animal and microbial toxins. Bangkok: Chulalongkorn; 1988. p. 115–26.Google Scholar
  19. Harrison RA. Development of venom toxin-specific antibodies by DNA immunisation: rationale and strategies to improve therapy of viper envenoming. Vaccine. 2004;22(13–14):1648–55.PubMedCrossRefGoogle Scholar
  20. Hung DZ, Yu YJ, Hsu CL, Lin TJ. Antivenom treatment and renal dysfunction in Russell’s viper snakebite in Taiwan: a case series. Trans R Soc Trop Med Hyg. 2006;100(5):489–94.PubMedCrossRefGoogle Scholar
  21. Isbister GK, Brown SG, MacDonald E, White J, Currie BJ. Australian Snakebite Project Investigators. Current use of Australian snake antivenoms and frequency of immediate-type hypersensitivity reactions and anaphylaxis. Med J Aust. 2008;188(8):473–6.PubMedGoogle Scholar
  22. Isbister GK, Shahmy S, Mohamed F, Abeysinghe C, Karunathilake H, Ariaratnam A. A randomised controlled trial of two infusion rates to decrease reactions to antivenom. PLoS One. 2012;7(6):e38739.PubMedCentralPubMedCrossRefGoogle Scholar
  23. Isbister G, Buckley N, Page C, Scorgie F, Lincz L, Seldon M, Brown S; the ASP Investigators. A randomised controlled trial of fresh frozen plasma for treating venom induced consumption coagulopathy in Australian snakebite (ASP-18). J Thromb Haemost. 2013a;11(7):1310-8.Google Scholar
  24. Isbister GK, Maduwage K, Shahmy S, Mohamed F, Abeysinghe C, Karunathilake H, Ariaratnam CA, Buckley NA. Diagnostic 20-min whole blood clotting test in Russell’s viper envenoming delays antivenom administration. QJM. 2013b;106(10):925-32.Google Scholar
  25. Karnchanachetanee C, Hanvivatvong O, Mahasandana S. Monospecific antivenin therapy in Russell’s viper bite. J Med Assoc Thai. 1994;77(6):293–7.PubMedGoogle Scholar
  26. Leeprasert W, Kaojarern S. Specific antivenom for Bungarus candidus. J Med Assoc Thai. 2007;90(7):1467–76.PubMedGoogle Scholar
  27. León G, Monge M, Rojas E, Lomonte B, Gutiérrez JM. Comparison between IgG and F(ab′)(2) polyvalent antivenoms: neutralization of systemic effects induced by Bothrops asper venom in mice, extravasation to muscle tissue, and potential for induction of adverse reactions. Toxicon. 2001;39(6):793–801.PubMedCrossRefGoogle Scholar
  28. Malasit P, Warrell DA, Chanthavanich P, Viravan C, Mongkolsapaya J, Singhthong B, Supich C. Prediction, prevention, and mechanism of early (anaphylactic) antivenom reactions in victims of snake bites. Br Med J (Clin Res Ed). 1986;292(6512):17–20.CrossRefGoogle Scholar
  29. Meenatchisundaram S, Parameswari G, Michael A, Ramalingam S. Neutralization of the pharmacological effects of cobra and krait venoms by chicken egg yolk antibodies. Toxicon. 2008;52(2):221–7.PubMedCrossRefGoogle Scholar
  30. Mitrakul C, Impun C. The hemorrhagic phenomena associated with green pit viper (Trimeresurus erythrurus and Trimeresurus popeorum) bites in children. A report of studies in elucidate their pathogenesis. Clin Pediatr. 1973;12(4):215–8.Google Scholar
  31. Mitrakul C, Juzi U, Pongrujikorn W. Antivenom therapy in Russell’s viper bite. Am J Clin Pathol. 1991;95(3):412–7.PubMedGoogle Scholar
  32. Nakashima K, Nobuhisa I, Deshimaru M, Nakai M, Ogawa T, Shimohigashi Y, Fukumaki Y, Hattori M, Sakaki Y, Hattori S, Ohno M. Accelerated evolution in the protein-coding regions is universal in crotalinae snake venom gland phospholipase A2 isozyme genes. Proc Natl Acad Sci USA. 1995;92(12):5605–9.PubMedCentralPubMedCrossRefGoogle Scholar
  33. Otero R, Gutiérrez JM, Rojas G, Núñez V, Díaz A, Miranda E, Uribe AF, Silva JF, Ospina JG, Medina Y, Toro MF, García ME, León G, García M, Lizano S, De La Torre J, Márquez J, Mena Y, González N, Arenas LC, Puzón A, Blanco N, Sierra A, Espinal ME, Lozano R, et al. A randomized blinded clinical trial of two antivenoms, prepared by caprylic acid or ammonium sulphate fractionation of IgG, in Bothrops and Porthidium snake bites in Colombia: correlation between safety and biochemical characteristics of antivenoms. Toxicon. 1999;37(6):895–908.PubMedCrossRefGoogle Scholar
  34. Otero R, León G, Gutiérrez JM, Rojas G, Toro MF, Barona J, Rodríguez V, Díaz A, Núñez V, Quintana JC, Ayala S, Mosquera D, Conrado LL, Fernández D, Arroyo Y, Paniagua CA, López M, Ospina CE, Alzate C, Fernández J, Meza JJ, Silva JF, Ramírez P, Fabra PE, Ramírez E, Córdoba E, Arrieta AB, Warrell DA, Theakston RD. Efficacy and safety of two whole IgG polyvalent antivenoms, refined by caprylic acid fractionation with or without beta-propiolactone, in the treatment of Bothrops asper bites in Colombia. Trans R Soc Trop Med Hyg. 2006;100(12):1173–82.PubMedCrossRefGoogle Scholar
  35. Otero-Patiño R, Cardoso JL, Higashi HG, Nunez V, Diaz A, Toro MF, Garcia ME, Sierra A, Garcia LF, Moreno AM, Medina MC, Castañeda N, Silva-Diaz JF, Murcia M, Cardenas SY, da Silva WD D. A randomized, blinded, comparative trial of one pepsin-digested and two whole IgG antivenoms for Bothrops snake bites in Uraba, Colombia. The Regional Group on Antivenom Therapy Research (REGATHER). Am J Trop Med Hyg. 1998;58(2):183–9.PubMedGoogle Scholar
  36. Otero-Patiño R, Segura A, Herrera M, Angulo Y, León G, Gutiérrez JM, Barona J, Estrada S, Pereañez A, Quintana JC, Vargas LJ, Gómez JP, Díaz A, Suárez AM, Fernández J, Ramírez P, Fabra P, Perea M, Fernández D, Arroyo Y, Betancur D, Pupo L, Córdoba EA, Ramírez CE, Arrieta AB, Rivero A, Mosquera DC, Conrado NL, Ortiz R. Comparative study of the efficacy and safety of two polyvalent, caprylic acid fractionated [IgG and F(ab′)2] antivenoms, in Bothrops asper bites in Colombia. Toxicon. 2012;59(2):344–55.PubMedCrossRefGoogle Scholar
  37. Pochanugool C, Limthongkul S, Wilde H. Management of Thai cobra bites with a single bolus of antivenin. Wilderness Environ Med. 1997;8(1):20–3.PubMedCrossRefGoogle Scholar
  38. Pongpit J, Limpawittayakul P, Juntiang J, Akkawat B, Rojnuckarin P. The role of prothrombin time (PT) in evaluating green pit viper (Cryptelytrops sp.) bitten patients. Trans R Soc Trop Med Hyg. 2012;106(7):415–8.PubMedCrossRefGoogle Scholar
  39. Premawardhena AP, de Silva CE, Fonseka MM, Gunatilake SB, de Silva HJ. Low dose subcutaneous adrenaline to prevent acute adverse reactions to antivenom serum in people bitten by snakes: randomised, placebo controlled trial. BMJ. 1999;318(7190):1041–3.PubMedCentralPubMedCrossRefGoogle Scholar
  40. Rojnuckarin P, Mahasandana S, Intragumtornchai T, Sutcharitchan P, Swasdikul D. Prognostic factors of green pit viper bites. Am J Trop Med Hyg. 1998;58(1):22–5.PubMedGoogle Scholar
  41. Rojnuckarin P, Chanthawibun W, Noiphrom J, Pakmanee N, Intragumtornchai T. A randomized, double-blind, placebo-controlled trial of antivenom for local effects of green pit viper bites. Trans R Soc Trop Med Hyg. 2006;100(9):879–84.PubMedCrossRefGoogle Scholar
  42. Rojnuckarin P, Banjongkit S, Chantawibun W, Akkawat B, Juntiang J, Noiphrom J, Pakmanee N, Intragumtornchai T. Green Pit Viper (Trimeresurus albolabris and T. macrops) venom antigenaemia and kinetics in human. Trop Doct 2007;37(4):207-10.Google Scholar
  43. Rojnuckarin P, Suteparuk S, Sibunruang S. Diagnosis and management of venomous snakebites in Southeast Asia. Asian Biomed. 2012;6(6):795–805.Google Scholar
  44. Sano-Martins IS, Fan HW, Castro SC, Tomy SC, Franca FO, Jorge MT, Kamiguti AS, Warrell DA, Theakston RD. Reliability of the simple 20 minute whole blood clotting test (WBCT20) as an indicator of low plasma fibrinogen concentration in patients envenomed by Bothrops snakes. Butantan Institute Antivenom Study Group. Toxicon. 1994;32(9):1045–50.PubMedCrossRefGoogle Scholar
  45. Thiansookon A, Rojnuckarin P. Low incidence of early reactions to horse-derived F(ab′)(2) antivenom for snakebites in Thailand. Acta Trop. 2008;105(2):203–5.PubMedCrossRefGoogle Scholar
  46. Visudhiphan S, Dumavibhat B, Trishnananda M. Prolonged defibrination syndrome after green pit viper bite with persisting venom activity in patient’s blood. Am J Clin Pathol. 1981;75(1):65–9.PubMedGoogle Scholar
  47. Wagstaff SC, Laing GD, Theakston RD, Papaspyridis C, Harrison RA. Bioinformatics and multiepitope DNA immunization to design rational snake antivenom. PLoS Med. 2006;3(6):e184.PubMedCentralPubMedCrossRefGoogle Scholar
  48. Warrell DA. Snake venoms in science and clinical medicine. 1. Russell’s viper: biology, venom and treatment of bites. Trans R Soc Trop Med Hyg. 1989;83(6):732–40.PubMedCrossRefGoogle Scholar
  49. Warrell DA. Guidelines for the management of snakebite. New Delhi: WHO regional office for Southeast Asia; 2010.Google Scholar
  50. WHO Expert Committee on Biological Standardization. WHO guidelines for the production, control and regulation of snake antivenom immunoglobulins. Geneva: WHO Press. Available from 2010.

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  1. 1.Faculty of MedicineChulalongkorn University and King Chulalongkorn Memorial HospitalBangkokThailand

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