Anti Venom – Classification, Symptoms and Effect

Anti Venom – Classification, Symptoms and Effect

Anti Venom – Anti-venom is often still the only effective treatment for envenomation- snake Anti-venom is made up of the antibodies from horses, sheep, goats, rabbits or dogs blood. Horses are more commonly used as more blood can be tapped.

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The first anti venom was developed in 1895 by French physician Albert Calmetti for the treatment of Indian Cobra bites. Anti venom is made by injecting a small amount of venom in an animal (usually a horse or sheep) to initiate an immune system response. The resulting antibodies are then harvested from animals blood. (White, Julian(1991)).

Anti venom is inejected into the patient intravenously, and works by binding to and neutral using venom enzymes. It cannot undo damage already caused by venom, so anti venom treatment should be sought as soon as possible.

Classification Of Anti Venom.

Anti venom is classified into 2 namely,

1.)  Monovalent anti venom and

2.)   Polyvalent anti venom.

1.)     Monovalent anti venom: This is made by injecting the venom of a specific specie of snake into an animal to develop the anti venom. This is effective against one specific snake species.

2.)     Polyvalent anti-venom: this is made by injecting the venom from a variety of different snake species into an animal to develop the anti venom. This is effective against a broad range of snake species (David Med) sel (Article 2005-2009).

As anti venoms are specific antibodies that neutralize the particular active toxin of venoms, the type of anti venoms  must be properly matched to the snake responsible for the bite. Anti venom have revolutionized the treatment for the more deadly snake envenomations. For example, the first horse anti venom against bites from Bungarus candidus in Vietnam, Changi the cause of a grouped of patient from 80% mortality to 100% recovery venomation snake bite Trinh Kx et al, (2005).

Anti venoms Production and Intervention to Prevent Anti venom Reaction.

Production of Anti venoms

The first available anti venom was produced against cobra venom by Calmette in 1894- Therapeutic anti venoms used for the treatment of snake envenomation are usually prepared in horses, although sheep and goats have also been used. Horses are easy to handle, thrive in most climate, yield large volumes of serum, and methods of purifying horse serum as well developed.

Collection of Hyperimmune Plasma.

The horse are bled from the jugular vain to a sodium citrate solution. Depending on the size of the horse, from 8-10 liters of blood are removed on each of two occasion, separated by 3 days. The plasma is separated from the corpuscles by continuous centrifugation and sufficient cresol is added to give a concentration of 0.3%-cresol present bacterial growth, it is convenient to add the cresol under agitation as a spray mixed with ether.

Enzymatic Digestion of Anti Venom

Effective immunization induces production of anti venom antibody which, in horses, belong to an 1gG subclass termed 1gG. 1gGr is highly glycosylated and had molecular weight of about 160kDa. It is generally accepted that the removal of FC fragment from 1gG prevented complement activation and so reduced the risk of adverse reaction.

1gG can be digested using either pepsin to produce facbj or papain to produce a smaller fab fragment. However, f(ab’)s is often used since it contains high avidity for antigen than fab fragment (s)

The specific restriction sites of both enzymes to 1gG are shown below. Thus adrenaline is the most likely intervention to have effect in the acute phase, with anti histamine and coticostenoids potentially avoiding relapse or preventing adverse effect of additional doses of antivenom.Malast 1986.

Malast P, Warrel, Chanthavanich P, Viram Van C, Monglkolsapoya J, Singhthong Po, Supich C, Prediction prevention and mechanism of early (anaphylactic) anti venom reaction Victoms of snake bites-BMJ 1986:292:17-20.Sutherland 1977

Sutherland S- serum reaction-an early analysis of commercial anti venoms and the possible role of anticomplementary activity in de-novo reaction to anti venoms and antitoxin-medical journal of Australia 1977:1:613-5.

Symptoms and Pathology Of Snake Envenomation

The symptoms, signs and gravity caused by snake venoms depends on various factors from the individual victim situation and snake venom.

  • The age and size of the victim.
  • The length of time the snake held on.
  • The amount of venom injected.
  • The species and size of snake involved.
  • Pathogens present in the snake mouth.
  • The extent of anger or fear that motivated the snake to strike.
  • The condition of the fangs and the venom gland.
  • The degree and kind of first aid treatment and subsequent medical care.

The clinical symptoms of snake bite occur in a wide spectrum with no bites resulting in minimal or no symptoms at all, while others are severe enough to result in systematic manifestation and even death- it is well known that most of the crotaline and viperine venome induce local myonecrosis as well as hemorrhage. Although elapid venom are usually considered acrurotoxic, cobra venom also cause necrosis without hemorrhage.

Fractionation of Anti Venom

Although crude serum was originally used for therapy, for many years anti venom has been purified by successive steps in order to reduce anaphylactic reaction dunwy, the treatment, the difficult and high cost of it to produce and it is short supply, the efficient fractionation process should be encouraged.

Removal of low molecular weight compounds and salts from anti venoms fractionation dialysis is a separation techniques commonly used remove precipitating agents remaining in the precipitate or supernatant during anti venom production C16,23,24), it also taken several days and can result in the anti venom contaminated with bacteria productivity endotoxins.

Gel filtration an effective purification method with no denaturing effect on proteins. It can also be used for the removal of salts and other low molecular weight compounds. However, get filtration is time consuming and not applicable to large scale plasma fractionation.

Intervention for Preventing Reaction to Snake Antivenom

The main problem with anti venom is that foreign animal proteins ( from immunized animal) frequently cause reaction which could be severe and life threatening. There are drugs that can be given with the anti venom to reduce these adverse effect, and these include adrenaline, antihistmines and stenoids. Anti venom reaction can be classified as early and late reactions.

Early anti venom reaction maybe mild (HCh, nausea, vomiting, diarrhea, headache or fever) but sometimes severe systemic anaphylaxis, develops with bronchospasm, hypotension or agioedema, occurring 10 minutes to 3 hours of administration. These early reaction are not 1gE mediated and are mostly caused by complement activation by 1gG aggregates. That are in the horse serum (Sutherland 1977, malasite 1986). These early reaction can be detected by skin or conjuctival sensitivity testes. (malasites, 1986). These reaction respond readily to subcutaneous adrenaline.

Late (serum sickness type) anti venom reaction can occur 1-2 weeks after treatment with anti venomous . it consists of fever, itching, arthralgia lympadenopathy and albuminuria. The rate reaction is caused by immune complex, and responds to treatment with steroids and anti histamines.

Adrenaling, antihistamines and corticosteroids corticosteroids are used concurrently with anti venom, each of these interventions has a different biological mode of action and each has different side or adverse effect.

  • Adrenaline (epinephrine) provides immediate physiological reversal or hyposensitivity effect seen in anaphylaxis. It stimulates the cardiosvascular system and can cause cardiac irrhythrmias.
  • Antihistamines drugs are often given with adrenaline and are thought to prevent anaphylactic relapse. They are relatively safe.
  • Corticosteroids are often given in anaphylaxis and suppress the immune system, but any effect will only come apparent 4-6 hours after administration of the drug.

Neurotoxic effect

The neurological symptoms are predominated in the elapid and hydrophid bites. Symptoms include ptosis impaired vision, slurred speech, difficulty swallowing, hypersalivation, paraesthesias, generalized muscle weakness, respiratory impairment and arrest. Onset of symptoms can be within minutes, but are typically develop over a few hours (80).

Necrotizing effect.

Myonecrosis, although common in most cases of snake envenomations, is most pronounced with crotalodae and viperidae venoms and can also be observed with Hydrophidae and Blapidae envenomation. The onset of gross myonecrosis is not as fast as the hemorrhagic effect, however, necrotic fibers can be observed histologically as early as the first hour after snake envenomation. Necrosis caused by snakes venom is really not limited to a local area; it also spreads to many internal organs such as the brains, lung kidney, hearth and liver at later stages, necrosis is seen at the site of the bite, with destruction of soft tissue (83), deep necrosis down the bones of a food or hand has often been reported. (84).

Edema-Forming Effect

Edema formation is a common feature of the cutaneous inflammatory response and is dependent on a synergism between mediator that increase vascular permeability and those that increase blood flow (85,86). The edema was maximum within 2hours, disappeared within 24 hours and was accompanied by thickening of inner derma layers and marked infiltration of neutropils into the underlying muscle layer (87). The capacity of exogenous-applied vasodilation such as calcitonin generated peptide (CGRP), prostaglanding E2, prostacyclin to potentiate inflammatory meditors is well known (88).

Hematotoxic Effect.

Hemorrhage is due to injury and subsequent lysis of endothelial cell plasma membrane. This cause the flow of blood and it’s component into the surrounding tissues. Venom of viperidae and crotalidae show pronounced hemorrhagic activities while Elapidae venoms are nonhemorrhagic, except ophiophagus harmah (kins cobra) venoms which has both hemorrhagic and proteolytic activity.

Venoms of crotalids and viperids are known to cause disturbance in blood coagulation and also thrombocytopenia. The pathogenesis of hemorrhage due to envenomation from snake bite involves, besides vessel wall damage caused by hemorrhagins, coagualation disturbance  by anticoagulants and coagulants and thrombocytopenia. The hemorrhagic effect of snake venom has been attributed to the action of proteolytic enzymes in the venoms (81,82)- in less severe cases, hemorrhage is limited to the cutaneous and subcutaneous tissue at the site of venom infection. In severe cases, herrmohage may even spread to cover a large portion of the involved extremity, affecting the muscle layer. Bleeding in several organs such as the brain, heart, lungs, intestine and kidneys is often encountered.

Use of Plants as Anti venom for the Treatment of Snake Venom

The subject of snake venom is one which has always attracted much attention and which has made great progress within the las century. The plants used include the vine called monkey ladder (Bauninia Cumanensis or excise, fabiceae) is pounded and put on the bite. Alternatively a tincture is made with a piece of vine and kept in a small bottle- other plant used include: mat root (Aristolochia rugosa), cat’s claw ( Pithocellobium unguis-cati), tobacco (Nicotiana tobacum), snake bush (Barlenia lupula), Obie seed (Cola nitida), and wild grigri root (Acrocomia rerensis). Some small bottle also contain the caterpillars (Battus polydamus, papilionidae) that eat tref leaves (Aristolochia tricobata). Emergency snake medicine one obtained by chewing a three-inch piece of the root of bosi canot (cecropia peltata) and administering this chewed-root solution to the person. Another native plant used is mardi grass ( Renealima alpine) (berries), which are crushed together with juice of wild cane (costus scaber) and given to the Victim. Making cut around the puncture or sucking out the venom has also been helpful.

Plants used to treat snake bites in (Trinidad and Tobago are made into the tincture with alcohol or olive oil and kept in rum flask called snake bottles.

Use of Nonovalent and Polyvalent Anti venom

Identification of the Culprit Snake.

It is essential that a diagnosis, based on identification of the snake and the presence or absence of symptoms and signs be made before treatment is instituted. The admitting diagnosis should indicate whether the patient had been bitten by a non venomous snake.

The identification of the species causing envenomation in a victim is a problem in the clinical study of snake bite, as most patients either do not bring the culprit snake with them to hospital, or do not see snake responsible and are thus incapable of identifying it. The selection of specific therapeutic anti venom

 

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