Antivenom

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For the Marvel Comics character, see Anti-Venom (comics).
Milking a snake for the production of antivenom.

Antivenom (or antivenin or antivenene) is a biological product used in the treatment of venomous bites or stings. Antivenom is created by milking venom from the desired snake, spider or insect. The venom is then diluted and injected into a horse, sheep, rabbit, or goat. The subject animal will undergo an immune response to the venom, producing antibodies against the venom's active molecule which can then be harvested from the animal's blood and used to treat envenomation. Internationally, antivenoms must conform to the standards of pharmacopoeia and the World Health Organization (WHO).[1]

Terminology[edit]

The name "antivenin" comes from the French word venin, meaning venom, which in turn was derived from Latin venenum, meaning poison.

Historically, the term antivenin was predominant around the world, its first published use being in 1895.[2] In 1981, the World Health Organization decided that the preferred terminology in the English language would be venom and antivenom rather than venin and antivenin or venen and antivenene.[3]

Therapeutic use[edit]

The principle of antivenom is based on that of vaccines, developed by Edward Jenner; however, instead of inducing immunity in the patient directly, it is induced in a host animal and the hyperimmunized serum is transfused into the patient.

Antivenoms can be classified into monovalent (when they are effective against a single species' venom) or polyvalent (when they are effective against a range of species, or several different species at the same time). The first antivenom for snakes (called an anti-ophidic serum) was developed by Albert Calmette, a French scientist of the Pasteur Institute working at its Indochine branch in 1895, against the Indian Cobra (Naja naja). In 1901, Vital Brazil, working at the Instituto Butantan in São Paulo, Brazil, developed the first monovalent and polyvalent antivenoms for Central and South American Crotalus and Bothrops genera, as well as for certain species of venomous spiders, scorpions, and frogs.

Antivenoms for therapeutic use are often preserved as freeze-dried ampoules, but some are available only in liquid form and must be kept refrigerated. They are not immediately inactivated by heat, however, so a minor gap in the cold chain is not disastrous. The majority of antivenoms (including all snake antivenoms) are administered intravenously; however, stonefish and redback spider antivenoms are given intramuscularly. The intramuscular route has been questioned in some situations as not uniformly effective.[4]

Antivenoms bind to and neutralize the venom, halting further damage, but do not reverse damage already done. Thus, they should be administered as soon as possible after the venom has been injected, but are of some benefit as long as venom is present in the body. Since the advent of antivenoms, some bites which were previously invariably fatal have become only rarely fatal provided that the antivenom is administered soon enough.

Antivenoms are purified by several processes but will still contain other serum proteins that can act as antigens. Some individuals may react to the antivenom with an immediate hypersensitivity reaction (anaphylaxis) or a delayed hypersensitivity (serum sickness) reaction and antivenom should, therefore, be used with caution. Despite this caution, antivenom is typically the sole effective treatment for a life-threatening condition, and once the precautions for managing these reactions are in place, an anaphylactoid reaction is not grounds to refuse to give antivenom if otherwise indicated. Although it is a popular myth that a person allergic to horses "cannot" be given antivenom, the side effects are manageable, and antivenom should be given as rapidly as the side effects can be managed.[5]

In the U.S. the only approved antivenom for pit viper (rattlesnake, copperhead and water moccasin) snakebite is based on a purified product made in sheep known as CroFab.[6] It was approved by the FDA in October, 2000. U.S. coral snake antivenom is no longer manufactured, and remaining stocks of in-date antivenom for coral snakebite expired in the Fall of 2009, leaving the U.S. without a coral snake antivenom. Efforts are being made to obtain approval for a coral snake antivenom produced in Mexico which would work against U.S. coral snakebite, but such approval remains speculative.[citation needed] In the absence of antivenom, all coral snakebite should be treated in a hospital by elective endotracheal intubation and mechanical ventilation until the effects of coral snake neurotoxins abate. It is important to remember that respiratory paralysis in coral snakebite can occur suddenly, often up to 12 or more hours after the bite, so intubation and ventilation should be employed in anticipation of respiratory failure and not after it occurs, when it may be too late.

Natural and acquired immunity[edit]

Although individuals can vary in their physiopathological response and sensitivity to animal venoms, there is no natural immunity to them in humans. Some ophiophagic animals are immune to the venoms produced by some species of venomous snakes, by the presence of antihemorrhagic and antineurotoxic factors in their blood.

It is quite possible to immunize a person directly with small and graded doses of venom rather than an animal. According to Greek history, King Mithridates did this in order to protect himself against attempts of poisoning, therefore this procedure is often called mithridatization. However, unlike a vaccination against disease which must only produce a latent immunity that can be roused in case of infection, to neutralize a sudden and large dose of venom requires maintaining a high level of circulating antibody (a hyperimmunized state), through repeated venom injections (typically every 21 days). The long-term health effects of this process have not been studied. Further, cytotoxic venom components can cause pain and scarring at the immunization site. Finally, the resistance is specific to the particular venom used; maintaining resistance to a variety of venoms requires multiple monthly venom injections. Thus, there is no practical purpose or favorable cost/benefit ratio for this, except for people like zoo handlers, researchers, and circus artists who deal closely with venomous animals. Mithridatization has been tried with success in Australia and Brazil and total immunity has been achieved even to multiple bites of extremely venomous cobras and pit vipers.

Because neurotoxic venoms must travel farther in the body to do harm and are produced in smaller quantities, it is easier to develop resistance to them than directly cytotoxic venoms (such as those of most vipers) that are injected in large quantity and do damage immediately upon injection.

Availability of antivenoms[edit]

Antivenoms have been developed for the venoms associated with the following animals:[7]

Spiders[edit]

AntivenomSpeciesCountry
Funnel web spider antivenomSydney funnel-web spiderAustralia
Soro antiaracnidicoBrazilian wandering spiderBrazil
Soro antiloxoscelicoRecluse spiderBrazil
Suero antiloxoscelicoChilean recluseChile
AracmynAll species of Loxosceles and LatrodectusMexico
Redback spider antivenomRedback spiderAustralia
Black widow antivenomBlack widow spiderUnited States
SAIMR Spider antivenomButton spiderSouth Africa
Anti Latrodectus antivenomBlack Widow spiderArgentina

Acarids[edit]

AntivenomSpeciesCountry
Tick antivenomParalysis tickAustralia

Insects[edit]

AntivenomSpeciesCountry
zoro antilonomicoLonomia obliqua caterpillarBrazil

Scorpions[edit]

AntivenomSpeciesCountry
AlacramynCentruroides limpidus, C. noxius, C. suffususMexico
Suero AntialacranCentruroides limpidus, C. noxius, C. suffususMexico
Tunisian polyvalent antivenomAll Iranian scorpionsTunisia
Anti-Scorpion Venom Serum I.P.(AScVS)Indian red scorpionIndia
Anti-scorpioniqueAndroctonus spp., Buthus spp.Algeria
Scorpion antivenomBlack scorpion, Buthus occitanusMorocco
Soro antiscorpionicoTityus spp.Brazil
SAIMR scorpion antiveninParabuthus spp.South Africa
Purified prevalent Anti-Scorpion Serum(equine)Leiurus spp.& Androctonus scorpionsEgypt

Marine animals[edit]

AntivenomSpeciesCountry
CSL box jellyfish antivenomBox jellyfishAustralia
CSL stonefish antivenomStonefishAustralia

Snakes[edit]

AntivenomSpeciesCountry
Polyvalent snake antivenomSouth American Rattlesnake Crotalus durissus and fer-de-lance Bothrops asperMexico (Instituto Bioclon)
Polyvalent snake antivenomSouth American Rattlesnake Crotalus durissus and fer-de-lance Bothrops asperSouth America
Polyvalent snake antivenomSaw-scaled Viper Echis carinatus, Russell's Viper Daboia russelli, Spectacled Cobra Naja naja, Common Krait Bungarus caeruleusIndia
Death adder antivenomDeath adderAustralia
Taipan antivenomTaipanAustralia
Black snake antivenomPseudechis spp.Australia
Tiger snake antivenomAustralian copperheads, Tiger snakes, Pseudechis spp., Rough scaled snakeAustralia
Brown snake antivenomBrown snakesAustralia
Polyvalent snake antivenomMany Australian snakesAustralia
Sea snake antivenomSea snakesAustralia
Vipera tabVipera spp.USA
Polyvalent crotalid antivenin (CroFab—Crotalidae Polyvalent Immune Fab (Ovine))North American pit vipers (all rattlesnakes, copperheads, and cottonmouths)North America
Soro antibotropicocrotalicoPit vipers and rattlesnakesBrazil
AntielapidicoCoral snakesBrazil
SAIMR polyvalent antivenomMambas, Cobras, Rinkhalses, Puff adders (Unsuitable small adders: B. worthingtoni, B. atropos, B. caudalis, B. cornuta, B. heraldica, B. inornata, B. peringueyi, B. schneideri, B. xeropaga)South Africa[8]
SAIMR echis antivenomSaw-scaled vipersSouth Africa
SAIMR Boomslang antivenomBoomslangSouth Africa
Panamerican serumCoral snakesCosta Rica
AnticoralCoral snakesCosta Rica
Anti-mipartitus antivenomCoral snakesCosta Rica
Anticoral monovalentCoral snakesCosta Rica
AntimicrurusCoral snakesArgentina
CoralmynCoral snakesMexico
Anti-micruricoscoralesCoral snakesColombia

Antivenom sources[edit]

The following groups assist in locating antivenoms:

References[edit]

  1. ^ Theakston RD, Warrell DA, Griffiths E (April 2003). "Report of a WHO workshop on the standardization and control of antivenoms". Toxicon 41 (5): 541–57. doi:10.1016/S0041-0101(02)00393-8. PMID 12676433. 
  2. ^ Merriam-Webster Dictionary Antivenin
  3. ^ World Health Organization (1981). Progress in the characterization of venoms and standardization of antivenoms. Geneva: WHO Offset Publications. p. 5. ISBN 92-4-170058-0. 
  4. ^ Isbister GK. (2002). "Failure of intramuscular antivenom in Redback spider envenoming". Emerg Med (Fremantle) 14 (4): 436–9. doi:10.1046/j.1442-2026.2002.00356.x. PMID 12534488. 
  5. ^ See, for example, the Antivenom Precautions paragraph of the Medication section of James Forster, MD, MS (2006-03-14). "Snake Envenomations, Sea". eMedicine Emergency Medicine (environmental). Archived from the original on 26 June 2006. Retrieved 2006-06-25. 
  6. ^ http://www.savagelabs.com/Products/CroFab/Home/crofab_frame.htm Link to PDF for full prescribing information, retrieved 11/11/12
  7. ^ "Appendix: Antivenom Tables". Clinical Toxicology 41 (3): 317–27. 2003. doi:10.1081/CLT-120021117. 
  8. ^ Spawls, S; Branch B (1995). The Dangerous Snakes of Africa. Ralph Curtis Books. Dubai: Oriental Press. p. 192. ISBN 0-88359-029-8. 

External links[edit]