Antivenom

Antivenom (or antivenin or antivenene) is a biological product used in the treatment of venomous bites or stings. Antivenom is created by injecting a small amount of the targeted venom into an animal such as a horse, sheep, goat, or rabbit; the subject animal will suffer 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 in others. Internationally, antivenoms must carefully meet the standards of Pharmacopoeia and WHO.

The name antivenin, comes from the French word venin meaning venom, and historically the word antivenin was predominant around the world; however, this usage is archaic in English. For the English language, the WHO decided in 1981 that the preferred terminology in the English language would be "venom" and "antivenom" rather than "venin/antivenin" or "venen/antivenene".

The principle of antivenom is based on that of vaccines, developed by Louis Pasteur; 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 given 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).

Vital Brazil, a Brazilian scientist, developed in 1901 the first monovalent and polyvalent antivenoms for Central and South American Crotalus, Bothrops and Elaps genera, as well as for certain species of venomous spiders, scorpions, and frogs. They were all developed in a Brazilian institution, the Instituto Butantan, located in Sao Paulo,Brazil.

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, 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.

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 inevitably 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.


Sheep are generally used in preference over horses now, however, as the potential for adverse immunological responses in humans from sheep-derived antibodies is generally somewhat less than that from horse-derived antibodies. The use of horses to raise antibodies - in Australia at least, where much antivenom research has been undertaken (by Sutherland and others for example) - has been attributed to the research base originally having been a large number of veterinary officers. These vets had, in many cases, returned from taking part in the Boer and First World Wars and were generally experienced with horses due to working with cavalry. The large animal vets were similarly oriented given the use of horses as a prime source of motive power and transport, especially in the rural setting. The overall experience with horses naturally made them the preferred subject in which to raise antibodies. It was not until later that the immuno-reactivity of certain horse serum proteins was assessed to be sufficiently problematic that alternatives in which to raise antibodies were investigated.

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 Cro-Fab. 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 will expire in the Fall of 2009 leaving the U.S. without a Coral snake antivenom at this time (January, 2009).

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. 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.