Antivenom

Antivenom

Milking a snake for the production of antivenom.
Clinical data
AHFS/Drugs.com	Monograph
Routes of administration	injection
ATC code	J06
Identifiers
Synonyms	antivenin, antivenene
ChemSpider	none

Antivenom, also known as antivenin, venom antiserum and antivenom immunoglobulin, is a medication made from antibodies which is used to treat certain venomous bites and stings. They are only recommended if there is significant toxicity or a high risk of toxicity. The specific antivenom needed depends on the species involved. It is given by injection.^[1]

Side effects may be severe. They include serum sickness, shortness of breath, and allergic reactions including anaphylaxis.^[1] Antivenom is made by collecting venom from the relevant animal and injecting small amount of it into a domestic animal. The antibodies that form are then collected from the domestic animal's blood and purified.^[2] Versions are available for spider bites, snake bites, fish stings, and scorpion stings.^[3]

Antivenom was first developed in the late 1800s and came into common use in the 1950s.^[2][4] They are on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.^[5] Depending on the type the wholesale cost in the developing world is 9.00 to 118.80 USD per vial.^[6] In the United States the wholesale cost is as high as 2,300 USD per dose.^[7][8]

Medical uses

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).

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.^[9]

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. Although rare, severe hypersensitivity reactions including anaphylaxis to antivenin are possible.^[10] 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.^[11]

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.^[12] 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. 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.

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]

Mechanism

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.

History

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. 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.^[15]

Availability

Internationally, antivenoms must conform to the standards of pharmacopoeia and the World Health Organization (WHO).^[16] Antivenoms have been developed for the venoms associated with the following animals:^[17]

There is an overall shortage of antivenom to treat snakebites. Because of this shortage, clinical researchers are looking at seeing if the amounts can is effective in severe neurotoxic snake envenoming.^[18]

Spiders

Acarids

Insects

Scorpions

Marine animals

Snakes

Terminology

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.^[20] 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.^[21]

References

External links

• Antivenom Index, 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 of the Miami-Dade Fire Rescue service