Antivenom

Antivenom

Milking a snake for the production of antivenom
Names
Other names	antivenin, antivenene
Clinical data
Routes of use	Injection
Defined daily dose	not established[1]
External links
AHFS/Drugs.com	Monograph
US NLM	Antivenom

Antivenom, also known as antivenin, venom antiserum, and antivenom immunoglobulin, is a medication made from antibodies that is used to treat certain venomous bites and stings.^[2] Antivenoms are recommended only if there is significant toxicity or a high risk of toxicity.^[2] The specific antivenom needed depends on the species involved.^[2] It is given by injection.^[2]

Side effects may be severe.^[2] They include serum sickness, shortness of breath, and allergic reactions including anaphylaxis.^[2] Antivenom is made by collecting venom from the relevant animal and injecting small amounts of it into a domestic animal.^[3] The antibodies that form are then collected from the domestic animal's blood and purified.^[3] Versions are available for spider bites, snake bites, fish stings, and scorpion stings.^[4]

Antivenom was first developed in the late 19th century and came into common use in the 1950s.^[3][5] It is on the World Health Organization's List of Essential Medicines.^[6] Depending on the type, the wholesale cost in the developing world is US$9.00–US$118.80 per vial.^[7] In the United States, the wholesale cost is as high as $2,300 per dose.^[8][9]

Medical uses

Antivenom is used to treat certain venomous bites and stings.^[2] They are recommended only if there is significant toxicity or a high risk of toxicity.^[2] The specific antivenom needed depends on the species involved.^[2]

In the US, approved antivenom, including for pit viper (rattlesnake, copperhead and water moccasin) snakebite, is based on a purified product made in sheep known as CroFab.^[10] 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.^[11][12]

As an alternative when conventional antivenom is not available, hospitals sometimes use an intravenous version of the antiparalytic drug neostigmine to delay the effects of neurotoxic envenomation through snakebite.^[13] Some promising research results have also been reported for administering the drug nasally as a "universal antivenom" for neurotoxic snakebite treatment.^[14]

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 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.^[15]

Antivenoms bind to and neutralize the venom, halting further damage, but do not reverse damage already done. Thus, they should be given 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 given soon enough.

Side effects

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. Although rare, severe hypersensitivity reactions including anaphylaxis to antivenin are possible.^[16] 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.^[17]

Mechanism

Antivenoms act by binding to and neutralizing venoms. The principle of antivenom is based on that of vaccines, developed by Edward Jenner; however, instead of inducing immunity in the person directly, it is induced in a host animal and the hyperimmunized serum is transfused into the person.^[18] The host animals may include horses, donkeys, goats, sheep, rabbits, chickens, llamas, and camels.^[19] In addition, opossums are being studied for antivenom production.^[20] Antivenoms for medical 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.

Some ophiophagic animals produce natural antidotes that render them immune to certain snake venoms. No human is immune to animal venom, but some individuals may be more or less susceptible to its effects.^[21]

A person can build up immunity to a particular venom through frequent low and increasing doses (about every 21 days), but this immunity is only in effect while he or she is undergoing the dose regime.^[21] According to Greek history, King Mithridates did this in order to protect himself against attempts of poisoning, therefore this procedure is often called mithridatism. However, cytotoxic venom causes injury even at low doses meant to build resistance and the long-term effects of venom dosing in general have not been studied.^[21] 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. Mithridatism 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 damage immediately upon injection.

History

Surgeon-Major Edward Nicholson wrote in the November 1870 Madras Medical Journal that he had witnessed a Burmese snake-catcher inoculating himself with cobra venom. However, the snake-catcher was unsure whether this was actually effective and therefore continued to treat his snakes with care. Nicholson, along with other Britons, began to consider that venom might provide its own cure. Although Scottish surgeon, Patrick Russell, had noted in the late 18th century that snakes were not affected by their own venom,^[22] it was not until the late 19th century that Joseph Frayer, Lawrence Waddell, and others began to consider venom-based remedies again. However, they and other naturalists working in India did not have the funding to fully develop their theories. Not until 1895 did Sir Thomas Fraser, Professor of Medicine at the University of Edinburgh, pick up Fayrer and Waddell's research to produce a serum to act against cobra venom. His 'Antivenin' was effective, but failed to make an impact as the public were focused on contemporary Pasteurian discoveries.^[23]

Another anti-ophidic serum was developed by Albert Calmette, a French scientist of the Pasteur Institute working at its Indochine branch in 1895, to treat the bites of the Indian Cobra (Naja naja).^[24]

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,^[25] as well as for certain species of venomous spiders, scorpions, and frogs.

In Australia, the Commonwealth Serum Laboratories (CSL) began antivenom research in the 1920s. CSL has developed antivenoms for the redback spider, funnel-web spiders and all deadly Australian snakes.^[26]

Availability

There is an overall shortage of antivenom to treat snakebites. Because of this shortage, clinical researchers are considering whether lower doses may be as effective as higher doses in severe neurotoxic snake envenoming.^[27]

Snake antivenom is complicated and expensive for manufacturers to produce.^[28] When weighed against profitability (especially for sale in poorer regions), the result is that many snake antivenoms, world-wide, are very expensive. Availability, from region to region, also varies.^[29]

Internationally, antivenoms must conform to the standards of pharmacopoeia and the World Health Organization (WHO).^[19][30] Antivenoms have been developed for the venoms associated with the following animals:^[31]

Terminology

The name "antivenin" comes from the French word venin, meaning venom, which in turn was derived from Latin venenum, meaning poison.^[35]

Historically, the term antivenin was predominant around the world, its first published use being in 1895.^[36] 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.^[37]

References

External links

• Antivenom Index Archived 2014-05-28 at the Wayback Machine Archived 2014-05-28 at the Wayback Machine, a joint project of the Association of Zoos and Aquariums and the American Association of Poison Control Centers which helps locate rare antivenoms
• Venom Response Program Archived 2013-11-01 at the Wayback Machine Archived 2013-11-01 at the Wayback Machine of the Miami-Dade Fire Rescue service