Snake Venom

Snake venom is the secretion of venomous salivary glands (homologous to the supralabial gland), which belong to the alveolar-tubular type. To the serous secretion of the venom glands themselves is added the mucous secretion of the epithelium of the excretory duct or other salivary glands. Snake venom in its fresh state is a thick, colorless, yellowish, or greenish liquid. When shaken, an aqueous solution of the venom foams strongly. In dry form, the venom is preserved for a very long time (up to 23 years). Snake venom is destroyed by the action of bacteria and oxidizing substances, as well as by putrefaction. Specific gravity 1.030–1.1082. The properties of snake venom differ in various species of snakes; for example, in vipers, the venom coagulates and loses toxicity at 72°, in Lachesis jararacucii at 110°, in L. mutis it coagulates at 65° but loses toxicity only at 120°, etc. Viperidae venom does not dialyze; filtration through a Chamberland candle halves its toxicity and does not noticeably affect Colubridae venom. The first attempt to isolate the active principle of snake venom was made by L. Bonaparte (1813), who, by precipitating viper venom with alcohol, obtained a water-soluble toxic substance he named viperine. A similar principle from rattlesnake venom was named crotaline (Weir Mitchell). Later, peptone-venom and globulin-venom were isolated from rattlesnake venom, the latter possessing the properties of the venom as a whole. There were other attempts at chemical isolation of the active principles of the venom (e.g., C. J. Martin isolated from Pseudechis venom a non-diffusing protein possessing the property of causing hemorrhages, and a diffusing albumin toxic to respiratory centers). According to Faust, snake venom consists of albumins, globulins, albumoses, peptones, mucin and mucin-like bodies, enzymes, formed elements (epithelium of glands and oral cavity), bacteria introduced from outside, and salts—chlorides and phosphates of calcium, magnesia, and ammonia. The enzymes of snake venom are unrelated to its toxicity. Faust isolated ophiotoxin (C₁₇H₂₆O₁₀) from cobra venom, and crotalotoxin (C₁₇H₂₆O₁₀ + 0.5 H₂O) from rattlesnake venom. These nitrogen-free substances are, according to Faust, animal sapotoxins. Faust recognizes only one active principle of snake venom, while other researchers speak of the polyvalence of snake venom toxins and classify them as toxalbumins. Along with attempts at chemical characterization of snake venom, some researchers have followed the path of determining the active principles of the venom by the nature of their physiological properties. In the venom of Vipera aspis, echidnase, echidnotoxin, and echidnovaccine were discovered. The first possesses only a local inflammatory effect, the second causes severe and fatal symptoms of poisoning, and the third possesses vaccinating properties. In a similar order, the presence of neurotoxins, cytotoxins, hemorrhagins, hemolysins, precipitins, and enzymes (see below) was also established in snake venom. The effect of snake venom on humans depends on the species of snake, the quantity and quality of the venom entering the wound, the location and depth of the wound, the condition of the snake, and some other collateral circumstances. When bitten by a viper, the wound has the appearance of two larger points (traces from the venomous fangs) and two parallel rows of smaller points (traces from the non-venomous teeth; see article 701, fig. 10). Picture of poisoning (see also Viper). A distinction is made between the local and general effect of snake venom. The snakes of the genus Lachesis are remarkable for the greatest intensity of the former. A few minutes after the bite, the affected area swells; severe hemorrhagic edema spreads to the entire limb and further to the trunk (gangrenous decay of tissue at the site of the bite is often observed, which can reach the point of complete exposure of the bones of the limb; see article 702, fig. 11). Severe local pain with a sensation of heat; nausea and vomiting, muscle weakness, drowsiness, cold sweat, lowering of body temperature, weak and frequent pulse. Hemorrhages in the mouth, ears, and on the skin are frequent. Death occurs in periods from less than an hour after the bite to 10–14 days later. The active principle of snake venom that causes local changes is called hemorrhagin; under its influence, hemorrhages also appear in parts of the body distant from the site of the bite (pericardium, endocardium, lungs, gastric mucosa, etc.). The bite of the spectacled cobra (Naja tripudians), on the contrary, causes insignificant local phenomena: at the site of the bite, a more or less intense burning is felt; redness and swelling appear around the wound, there is no acute pain. General symptoms of poisoning appear after half an hour. General fatigue, drowsiness, weakness in the legs are felt, consciousness becomes clouded. Further, profuse salivation, paralysis of the tongue and larynx are noted; the bitten person can neither speak nor swallow. Nausea and vomiting are frequent. Heart activity is weakened. Paralysis becomes general. Spontaneous movements are impossible. Breathing slows down and weakens. Finally, it ceases due to paralysis of the nerve endings of the respiratory muscles in the absence or presence of convulsions. Then the heart stops, and 2–7 hours after the bite, the poisoned person dies. In milder poisoning, severe symptoms do not develop, and the patient quickly recovers; the same happens if they survive the period of paralysis. The venom is removed by the kidneys. There is no protein in the urine. The venom of the spectacled cobra is rich in neurotoxin, which acts electively on the nervous system; the venom of some rattlesnakes (e.g., Crotalus terrificus) is distinguished by the same. In poisonings by the venom of coral snakes (Elaps), there are no local phenomena. Among the painful symptoms, the most important are severe pain, lacrimation, profuse salivation, diarrhea, tremors, muscle weakness, and paralysis. It is necessary to note that snake venom is very diverse in its properties and that snake venoms are not identical even in closely related species of the same genus. This complicates the pharmacological grouping of snake venom. There is no strict proportionality between the size of the dose of snake venom and the speed of death. The time of death is shortened only to certain limits, and a further increase in the dose of venom in the same direction no longer acts. Regarding the degree of toxicity of snake venom, one can judge by the following examples: the same amount of rattlesnake venom kills 10 snakes, 24 dogs (25 kg each), 25 bulls, 60 horses, 600 rabbits, 800 rats, 2,000 guinea pigs, and 300,000 pigeons (Brazil). 1 g of cobra venom is lethal for 1,250 kg of dogs, 1,430 kg of rats, 2,000 kg of rabbits, 2,500 kg of guinea pigs, and 8,333 kg of horses. 1 g of dry venom of the same snake is lethal for 20,000 kg of horses and 10,000 kg of humans (Calmette). The course of poisoning depends on the place of entry of the venom. If a part of the body rich in vessels is wounded, the venom is quickly absorbed into the blood, which affects the speed of the course of the disease. Lightning-fast poisoning occurs with the accidental biting of a large vein by a snake. The venom enters the blood directly, which coagulates from its action. Intact healthy skin and the same mucous membrane do not absorb the venom of most snakes. When swallowed, the venom of Colubridae has no effect, while the venom of Viperidae in sufficient doses causes inflammation of the mucosa and gastrointestinal hemorrhages. Pathological changes under the influence of snake venom develop in various organs: the heart muscle and liver cells undergo fatty degeneration; in the kidneys, there is effusion in Bowman's capsules, necrosis and desquamation of the epithelium; in the lungs, a multitude of small infarcts; in nerve cells, granular disintegration of Nissl bodies and acute fatty degeneration of some cells of the anterior horns of the spinal cord. The effect of snake venom on the blood is different. The venom of the spectacled cobra, pit viper (Ancistrodon), rattlesnake (Crotalus adamanteus), and others possesses anticoagulant properties (in vivo and in vitro); on the contrary, coagulating properties are inherent in the snake venom of various Lachesis, saw-scaled viper (Echis carinata), Crotalus terrificus, Ancistrodon blomhoffi, various Vipera, and others. The hemolyzing power of snake venom is different for different animals. For the possibility of hemolysis, snake venom must be activated by the addition of heated normal horse serum or lecithin (formation of toxolecithid). The hemolysins of snake venom are not identical to its neurotoxin. The agglutinins of snake venom, in turn, are not identical to either the hemolysin or the toxic principles of the venom. The agglutinating principle of snake venom is the same for erythrocytes and leukocytes, but leukolysins are not identical to hemolysins. Snake venom contains cytolysins that act on the endothelium of vessels, which causes the appearance of hemorrhages in poisoning (Lachesis). In vitro, the venom of the cobra and other snakes dissolves the cells of the liver, kidneys, and spleen of humans and acts similarly on the cholera vibrio, diphtheria bacillus, and other microbes. The bacteriolysins of snake venom are independent of its proteolytic principle and hemolysin. There is no exact statistics on human mortality from snake venom. It is indicated that 20,000 people die annually in India from bites by venomous snakes, which is highly doubtful. In Brazil (according to Brazil), venomous snakes bite about 24,000 people a year with 4,800 fatal outcomes. Statistics on bites by venomous snakes in the USSR have not been and are not being kept. The frequency of bites does not always coincide with the frequency of the presence of venomous snakes. For example, in Primorye and Manchuria, pit vipers (Ancistrodon) are frequent and numerous, but very little is known about bites by them to humans or animals: in the hospital with...

In Chernigovka of the Nikolsk-Ussuriysky Uyezd, not a single case of a bite requiring medical assistance was noted over 7 years. In the Posyet district, up to 10 cases of bites by venomous snakes occur annually in one of the outpatient clinics. Unfortunately, doctors leave the majority of cases of human poisoning by snakes in our country without description or registration in the press. Measures to combat venomous snakes, which ultimately also serve as prophylaxis for snake bites, boil down to announcing a bounty for the head of a killed venomous snake. In France, in one district in 1890, 67,620 vipers were killed at a price of 25-50 centimes apiece. In Germany, they paid up to 2 marks. In Bosnia and Herzegovina in 1906, 25,483 snakes were destroyed, half of which were Vipera ammodytes. However, the advisability of mass destruction of certain venomous snakes is disputed by some authors. Regarding the pit vipers of the Far East, A. Emelyanov says that they practically "pose almost no danger either to humans or to their domestic animals," but at the same time, these snakes devour a mass of field mice—important pests of agriculture. Likewise, some authors consider the opinion about the general harmfulness and danger of the viper to be exaggerated, but along with these species, there are also those that are very dangerous to humans. Other authors, however, say that "it is better to kill all snakes, equally venomous and non-venomous, than to allow even one person to die from one of them." Protecting the enemies of venomous snakes—hedgehogs, polecats, and various birds (short-toed snake eagle, lesser spotted eagle, buzzard, raven, magpies, jays, and others)—can have some significance. Among natural disasters, forest and steppe fires are destructive to snakes. Since the chances of snake bites on the legs are most frequent, personal prophylaxis should consist of wearing boots with shafts made of thick leather, which our venomous snakes are unable to bite through. The most appropriate and effective method would be vaccination with weakened venom of one or another group of snakes. But it is used (purely intuitively) only by some wild tribes. It is also noted here that people acquire immunity to snake venom after having successfully survived a bite from the corresponding venomous snake. Treatment of snake venom poisoning. The Brahmins of India apply a "snake stone," prepared from animal charcoal, to the bite site. In other places, various quack remedies and incantations are used for treatment. In case of a bite by a venomous snake, a ligature (made of a scarf, towel, belt, rope, etc.) should be applied above the wound site, which is tightened firmly to stop blood circulation. The ligature is kept on for no more than half an hour. During this time, it is necessary to remove or neutralize the snake venom. Sucking blood from the wound with the mouth can be dangerous if the oral mucosa is bleeding anywhere (do not swallow the blood!). A suction cup acts more safely and reliably; before its immediate application, the wound is widened with a knife. To destroy the snake venom, a 1% solution of potassium permanganate (0.5 cm³ in three or four places around the wound) or gold chloride or a 2% solution of chlorinated lime is injected as soon as possible into the wound itself or its vicinity. Among symptomatic agents, alcohol is used internally (but not during serum treatment), although there are objections to it; camphor and adrenaline are injected. It is recommended to take a large amount of hot tea or coffee. The most reliable treatment is with specific anti-snake venom sera (Sewall, 1887; Kaufmann, Fraser, Phisalix and Bertrand, Calmette, Great Medical Encyclopedia, vol. X, Brazil, Kraus, and others). The production of therapeutic sera is based on the development of powerful antibodies in an animal's body during repeated injections of increasing doses of snake venom, starting with a sublethal one. Calmette developed the following method: horses are injected into the jugular vein with increasing doses of cobra venom and, over 16 months, are made resistant to a single injection of 2 g of dry venom, i.e., to a dose exceeding the normal lethal dose by 80 times. Twelve days after the final injection, blood is taken in three stages: the first time—8 liters, after 5 days—6 liters, and after another 5 days—the same amount. 2 cm³ of serum from an immunized horse, when injected into a rabbit's ear vein, should protect it from the effect of 1 mg of venom injected into the vein of the other ear. A control animal dies from such a dose in half an hour. The serum is aseptically bottled in 10 cm³ sterile vials and heated in a water bath for 1 hour at 58° for three consecutive days. It can be stored for two years. The serum can also be preserved in dry form in sealed glass tubes. Before use, it is dissolved: 1 part in 10 parts of sterile water. Due to the pharmacological difference between "hemorrhagic" and "neurotoxic" principles and the predominance of one or the other in the venom of different snake species, it is necessary to prepare special sera for them, since anti-cobra serum is ineffective, for example, in treating poisoning by Lachesis venom. Specific monovalent sera, effective against one type of snake venom, are less practical in places where species of snakes with different pharmacological properties of venom are found. Therefore, they also began to prepare polyvalent universal sera by immunizing a horse with different types of snake venom. The fabrication of such sera is carried out in various serotherapeutic and Pasteur institutes (Lille, London, Algiers, India, etc.). Regarding European vipers, Calmette's special "ER" serum and serum against the Brazilian Lachesis jararaca are effective. The serum is injected as soon as possible after the bite under the skin of the abdomen or back. The success of such specific treatment is undoubted: in Brazil, by using it, it was possible to reduce mortality from snake venom from 25% to 3%. Use of snake venom. In Egypt, asps were used for executions. Hottentots cut out the venom glands of Bitis arietans or grind its head to prepare arrow poison. Levin treated leprosy with rattlesnake venom and found that lepers tolerate doses that are lethal to a normal person. Calmette and Mezie attempted to use the same venom to treat epilepsy and sometimes achieved a reduction in the number of seizures. Phisalix (M. Phisalix) tried to immunize rabbits with Vipera aspis venom against rabies. Finally, the reaction of activating cobra venom for hemolysis by adding human blood serum was sometimes used for differential diagnosis. Normally, serum is devoid of lecithin, and there is no reaction. In general paralysis and dementia praecox, lecithin passes into the blood, and the serum often activates the venom, while in depressive mental illnesses, such an effect is very rare. This reaction is not specific.