SNAKE BITES VENOM AND ANTI-VENOM

Snake venom is modified saliva and is produced by modified saliva glands. Venoms are rich in hydrolithic enzymes, a complex mix of polypeptides, nucleases, peptidases, etc., which help digest the snake's prey. Some of them also enhance or contribute to the toxic effect of the venom. As early as 1949 it was shown that an enzyme from the Bothrops species produces a vasodilation resulting from the production of a hypotensor neuropeptide, bradykinin. This had important consequences for man leading to drugs for the control of blood pressure. The proteins that can kill or immobilize prey vary and differ in their effect and the percentages in which they are present in venom. Some toxins and their effects Examples Action a-Bungarotoxin, a-toxin, Blocks neuromuscular transmission by erabutoxin, cobrotoxin linking, like curare, onto the cholinergic receptor found on the skeletal muscle fibers -Toxin Blocks some of the central nervous system's cholinergic receptors Notexin, ammodytoxin, Blocks neuromuscular transmission by bungarotoxin, crotoxin, taipoxin keeping nerve ends from liberating acetylcholine. Possible interaction with potassium canal sensitive to voltage. Dendrotoxin, toxins and Increases amount of acetylcholine liberated by nerve ends. Possible interaction with potassium canal sensitive to voltage. Disturbs the plasma membranes of some cells like cardiac fibers and results to lysis. Leads to cardiac arrest.

Class -Neiurotoxins

-Toxins -Neurotoxins

Dendrotoxins

Cardiotoxins

-Toxin, cariotoxin, cytotoxin

Sarafotoxins Mytotoxins

Sarafotoxins a, b and c

Hemorrgines

Powerful vasoconstrictors affecting the cardiac system as a whole leading to cardiac arrest. Myotoxin-a1, crotamine Leads to muscular degeneration by interacting with a sodium canal dependent on voltage Phospholipase A2 Leads to muscular degeneration Mucrotoxin A, hemorragic toxins Leads to very serious hemorrhages by a,b,c, HT1 and HT2 altering the vessel walls.

The protein-like nature of snake venom was established by Napoleon Bonaparte's brother, Lucien in 1843. Proteins constitute the major portion of venom's dry weight - 90% or more. Snake venom is a cocktail of hundreds, sometimes thousands, of different proteins and enzymes. Many of these proteins are harmless but a percentage of them are toxins. The composition of these toxins vary widely from species to species. This complexity accounts for the widely differing effects of snakebite. To some degree some or all of these toxins are present in all snake venoms. Snake venom can be divided into 4 main groups according to its clinical effect on the victim. Types of Venom: Cytotoxic Direct toxic effects on the cells that causes cell lyses (destruction) Neurotoxic - The venom blocks the transfer of the nervous impulse from the nerve tissue to the muscle. Haemotoxic - The venom interferes with the clotting mechanism in the blood with the attendant complications of uncontrolled bleeding. Combination - A syndrome develops with a mixed picture between cytotoxic and neurotoxic symptoms.

Cytotoxic venom
The presenting symptom of these bites is a painful swelling commencing at the bite site that is warm, often tender and spreads mainly up the limb or tissue. This may lead to swollen lymph glands within 2 hours after the bite. Local complications include blistering, necrosis (dead tissue), localized bleeding, and infection. The swelling may be so severe that it can cause compartment syndrome. This is a syndrome where the venom causes severe swelling of the underlying muscles. The muscles are surrounded by an inelastic sheath and when the muscle swells it compresses the arteries and nerves that runs through the muscles within the sheath. The oxygen rich blood that flows through the arteries cannot reach the tissue under the occluded arteries and the tissue will then die due to the oxygen shortage. If this condition is not corrected as a matter of urgency within a period of 4 hours (usually surgery is needed to release the intra compartmental pressure by splitting the inelastic sheath) it may lead to tissue loss or even amputation in severe cases. Compartment syndrome must be seriously suspected when the pain in the tissue below the swelling increases in severity and develops a pins and needles feeling or numbness. An absent pulse below the swelling is usually a late sign and requires urgent surgical intervention.

Another frequent regional complication from cytotoxic venom is the development of a deep vein thrombosis (blood clot) in the affected limb. Systemic effects of the venom include hypo tension (low blood pressure), fluid on the lungs and difficulty breathing (edema and ARDS), and a low platelet count, which can lead to bleeding (DIC). Systemic venom action producing edema and heart conduction defects has only been documented in Gaboon adder bites, which are uncommon in South Africa as this snake is only found around St Lucia. The groups of snakes that has cytotoxic venom include the Gaboon adder, Puff adder, Mozambique spitting cobra, Stiletto snake, Night adder and other smaller adders.

Neurotoxic venom
The neurotoxic venom interferes with the impulse transfer from nerve endings to skeletal muscles leading to paralysis. The signs and symptoms of neurotoxic envenomation can deteriorate rapidly from a feeling of numbness around the mouth (perioral anesthesia) to sweating, drop in blood pressure, difficulty in swallowing (saliva running from the mouth) to complete respiratory arrest where the patient stops breathing, and eventually without medical intervention, to death. Within a few minutes from a mamba bite there is perioral anesthesia that progress to relentless widespread muscle weakness leading to respiratory failure in 60-70% of cases. Non spitting cobras (Cape, Snouted and Forest) leads to early swelling around the bite site, a window period where the patient is apparently normal followed by fairly rapid onset of inadequate respiration due to paralysis (about 50% of cases). The group of snakes with neurotoxic venom include Black and Green Mambas and the non Spitting Cobras: Cape, Snouted, Forest.

Haemotoxic venom
The venom interferes with the clotting cascade and by lowering the platelets in the blood. The Boomslang and Vine snakes are the two snakes most commonly responsible for bites to snake handlers. Their venoms are exclusively haemotoxic and acts on the clotting cascade preventing blood clotting which can cause internal and external bleeding. Fortunately both snakes are back fanged snakes and their bites are limited to hands and feet. Boomslang induced clotting dysfunction is of slow onset, with potential death only occurring after several days. This allows time to get the Boom slang specific antivenom from the manufactures (phone: 011-882-9940).

There is currently no antivenom available for the Vine snake. Although Gaboon and Puff adderss has got cytotoxic venom, it can also cause bleeding by reducing the platelets.

Combination venom
A syndrome of a mixed picture of cytotoxic and neurotoxic signs and symptoms are found in some snakebites. Among these symptoms are cranial nerves dysfunction (Cranial nerves mainly supplies the organs of the face, throat and neck, heart and intestines), which uncommonly leads to other skeletal muscle weakness and respiratory failure. Venom from a Berg adder bite can cause loss of taste and smell. The group of snakes with combination venom effects includes: Rinkhals, Berg adder, Garter snake, Shield-nosed snake

Allergic reaction
Exposure to venom either by skin contact or envenomation through a snakebite can cause an acute allergic reaction to patients that were previously exposed to the venom. The reaction can be compared similarly to an allergic reaction from a bee sting, ranging from a mild reaction to death within minutes after the bite. These type of reactions are usually limited to snake handlers or persons that was previously bitten by a snake. In the above group of patients that deteriorates rapidly after a bite an allergic reaction must be seriously considered. There is a huge difference in treatment between envenomation by snakebite and an allergic reaction against the venom. Symptomatic snake bites are usually treated by antivenom where as an allergic reaction is treated with adrenaline.

Anti-venoms
Anti-venoms were first produced a century or more ago. Albert Calmette demonstrated that it was possible to "hyper-immunise" an animal against snakebite by graduated and increased regular dosage of that animal with the venom of that snake. He further demonstrated that a second animal could be saved after snakebite by introducing the serum of the immunised creature. This discovery is still the basis of the production of modern anti-venoms. A few modern modifications have been introduced - such as the neutralisation of the venom with formaldahyde before use on the animal. This removes a lot of the earlier suffering such animals endured.

The animal of choice is the horse. Increasing doses of venom are injected until the animal becomes hyper-immunised and thereafter blood is drawn and the serum removed. The rest of the blood is transfused back into the animal. The serum then passes through various stages of refinement before it is released for use on humans. The serum contains immunoglobulins and these are digested by pepsin to isolate the antigen that neutralises the venom. These antivenoms are very safe - however they are an animal protein derivative and a small percentage of people react dangerously to it. They display a hyper-allergic reaction which leads to anaphylactic shock which can kill. In a hospital situation a cocktail of anti-histamines and hydro-cortisones would be administered prophylactically. Then a small test sample of antivenom is administered and the reaction to it noted before a full dose is injected or preferably dripped into the patient in an intravenous solution. The production of serum from a single venom is known as a "monovalent" anti-venom and is efficacious only on the snake from which the venom comes. When a cocktail of venoms is used in the hyper-immunisation process the serum produced is a "polyvalent" serum and is effective against a range of venoms. However the addition of each venom causes a loss of efficiency and potency in the anti-venom as a whole. So a delicate balance of similar venoms is usually used to produce an antivenom against the known snakes of a given area. Snake venoms play an important role in the production of diverse medications that have saved numerous lives.

Management
An analysis of 4 rural snakebite series involving 911 patients by Dr Roger Blaylock, one of the foremost authorities in South Africa on the management of snakebites, showed the following.

16% had no envenomation 77% developed progressive painful swelling 6% progressive weakness <1% bleeding

Prevention
Common sense is the gold standard in preventing snakebites:

Wear boots that covers the ankle and loose hanging long pants. Most of the snakebites are on the feet, ankle and lower leg. Dont step over an obstacle if you cannot see what is on the other side. Dont put your hand into a hole when you cant see what is inside. Dont handle snakes if you are not a professional snake handler.

Dont confront a dangerous snake. If you encounter a snake back of as fast as possible keeping your eye on the snake. However if you are so close that you are within striking distance and the snake is already engaged to strike stand dead still until the snake withdraws. Snakes only strike at movement Prevent nocturnal bites by using a light, wearing footwear and sleeping in a snake proof dwelling (zip up tents). Be careful of handling dead snakes as some elapids, notably the Rinkhals, may feign death.

Medical management
The majority of patients cannot correctly identify the snake even with the help of pictures. Because of this Dr Blaylock divided the snakebite victims into the following 3 groups according to the clinical picture at presentation. 1. Painful Progressive Swelling 2. Progressive Weakness 3. Bleeding The syndromic management of these patients with antivenom simplifies the treatment of snakebites drastically. Antivenom is given in each of these groups according to set criteria based on signs and symptoms.

Patients also receive supportive treatment according to the organ systems affected e.g. ventilation support for patients with respiratory failure and platelets and blood clotting components for patients with active bleeding

First Aid
Getting the patient to medical help is the major priority. General principles to consider:

Remain calm and react in a logical way. Remember: very few people die from snake bite Keep the patient calm and reassured. Immobilize the patient as far as possible and dont waste time in delaying his transport to the nearest medical facility. Do not give the patient anything to drink or eat especially not alcohol.

Incision, suction, cryotherapy (freezing of bite site), electrotherapy, topical or ingested medication is of no value. Do not waste time by searching for and trying to kill the snake Pressure immobilization bandaging is not recommended as it may aggravate or precipitate tissue necrosis (death/destruction) or compartment syndrome as the majority of snakebites presents with progressive swelling. An arterial tourniquet is of value in known non spitting cobra and mamba bites and should be reserved for cases with positive identification of one of the above group of snakes. Tourniquet application can cause severe underlying tissue damage if applied wrongly .It is best to leave it to people with the necessary training on tourniquet application. The tourniquet must be released every 30 min and not be kept on for longer than 2 hours. Patients who cannot swallow their saliva must be placed in the recovery position and closely observed for respiratory failure. The saliva can accumulate in the patients throat and prevents air entry in the lungs. If left unattended the patient can drown in his own saliva . Try to remove as much as possible of the saliva in the victims airways by either sucking or finger sweep. With finger sweep, wrap a gauze swab or a piece of absorbable clothing around your index and middle finger, and sweep your finger through the patients mouth and throat to remove as much as possible of the saliva manually When the patient becomes unresponsive or start having difficulties breathing, immediately start with CPR. Do not inject antivenom, the doctor should do that. Antivenom is very effective and should not be withheld to a patient with signs and symptoms that necessitate the administration of antivenom. However, the antivenom can cause a potentially severe allergic reaction. The incidence of potentially severe acute allergic reactions depends on the clinical indication for its administration ranging from 8% when given to patients with progressive weakness to 20% for patients with painful progressive swelling. Patients with bleeding from Boom slang bites can have an allergic reaction to the antivenom in up to 70% of cases. Antivenom must preferably be given under medical supervision with adrenaline at the bedside. All snakebite victims should be hospitalized for at least 24 hours. Symptoms and signs of severe local or systemic poisoning occur sooner in children than in adults due to a higher venom concentration. The indications for antivenom administrations occur sooner and more frequently in children than in adults. The same amount of antivenom is given to children and adults. The venom from baby snakes is just as lethal as that of the adult snakes. The severity of the signs and symptoms and rate of deterioration of a victim, depends on the amount of venom injected during the bite and bite site. The closer the bites site to the heart the faster the signs and symptoms will appear. If the venom is injected directly into a vessel, rapid deterioration in the victims condition may be expected

Venom in the eyes

The Rinkhals and Mozambique spitting cobra are responsible for nearly all the cases of eye envenomation in Southern Africa. The Black spitting cobra and the Western barred spiting cobra can also be responsible for spitting in their victims eyes, although reported cases are uncommon.

The Rinkhals and Mozambique spitting cobra can spit accurately over a distance of up to 2 meters. The Rinkhals needs to hood its neck to be able to spit whereas the Mozambique spitting cobra can spit from any position.

The eye is very vascular and venom in the eye can be rapidly absorbed. This can cause severe inflammation and painful spasm of the eyelid. If left untreated it may progress to inflammation of the cornea and ulcer formation, which may cause blindness. If correctly treated the effects are usually benign with full recovery expected within a week.

General first aid principles for venom in the eyes

Wipe the venom from the face Wash the eyes with copious amounts of fluid for at least ten minutes If water is not available any type of fluid can be used which is not harmful to the eyes like cold drinks, milk, beer etc Place an eye pad over the eyes if available and transport the victim to the nearest medical facility It is advisable to let an ophthalmologist examine the eyes Antivenom, either topical or systemic, is not indicated