As far as is known, the following substances mainly enter into composition of the venom–fibrin ferments, proteolytic ferments, cytolysins acting upon the red cells, leucocytes, epithelial cells, nerve cells and agglutinins and neurotoxin having a selective action on all the nerve tissue specially in the respiratory and vascular centres. If has been observed that the neurotoxin in cobra venom has a special affinity for the respiratory centre and for the neighbouring gangalia of the 9th., 10th, 11th., and 12th. cranial nerves, and a curare-like effect on the motor endplates of the muscles. the krait neurotoxin has a selective action on the anterior horn cells of the spinal cord.
It has been found that an adult cobra injects 211.3 mgm. of the venom at a single, bite, while the minimum lethal dose of cobra venom for a man of 60 kilogrammes weight is about 15 mgms., causing death in three hours. This shows that the cobra injects about 10 to 15 times the minimum lethal dose. The toxicity of the venom varies with different kinds of animals. It is relatively less toxic to frogs, cats and rats but fatal to dogs, rabbits and men.
When given intravenously the venom produces an immediate effect, the animal dying within a few minutes of respiratory failure, provided a large enough dose is given. The absorption is slower when the venom is given by the subcutaneous or intramuscular routes, death taking place in 4 to 24 hours. The venom is not absorbed at all from the gastrointestinal tract or other mucous membranes.
The venom has no effect on the activity of salivary, gastric and pancreatic secretions of man in vitro. It slightly increases the tone of the musculature of the gastro-intestinal tract in cats and rabbits.
Injections of sub-lethal doses of the venom produce a small but persistent rise of blood pressure in experimental animals. this rise is not due to any stimulant action on the accelerator mechanism of the heart or on the myocardium. None of the concentrations of the venom, however high or low, produce definite stimulation of the heart specially when it is failing. Very large doses appear to act directly on the heart producing a marked depression and stoppage. The rise of blood pressure appears to be associated with the stimulation of the vasomotor centre in the medulla, as it is absent in decerebrated animals.
The fall of blood pressure by large doses has been shown to be due to paralysis of the vasomotor centre. The main action of the venom in lethal and sub-lethal doses on the animals is on the respiratory centre, the effect being one of initial stimulation and final paralysis. The venom appears to have no effect on the motor endplates in the diaphragm or other respiratory muscles. Observation on animals shows that the venom produces initial stimulation of the higher parts of the brain followed by paralysis.
Snakes and their venoms have been regarded as of great medicinal value in India and their use is from time immemorial. The Hindu physicians obtain the poison by making the reptile bite a piece of wood and the poison flowing out is collected in plantain leaf. It is preserved by drying or rubbing with a little mustard oil and spreading it on the leaf. It is chiefly the venom of the Indian cobra that is used by Hindu physicians.
In Western medicine, rattle snake venom (crotaline) has been used in a number of diseases. It is said to have been employed beneficially in the treatment of pulmonary tuberculosis, acute pneumonia, pulmonary gangrene, asthma, chronic spasmodic cough, hoarseness, neuralgia, chorea, epilepsy, hystero-epilepsy and haemophilia. Its use in Therapeutics is based on its depressing properties on the nerve cells.
The application of the venom in medicine may be based on the presence of the following active principles:–(a) Neurotoxin. (b) Cytolysin (with absorption of granular tissue). (c) Coagulative and haemorrhagic enzymes (production of protein and histamine-like shock). (d) Protective properties against Epilepsy.
Neorotoxin.–The neurotoxin principle is present in all snake-venoms though it predominates in cobra venom of other vipers and other snakes. This principle has a strong depressant action on the higher centres. In small doses it has an irritant action, but in large doses or on prolonged contact it produces paralysis of both the sensory and motor endplates. The venom therefore is graduated doses may be sued to depress the higher psychical centres and is useful in delirium, hallucination, aphasia, and melancholia.
Improvement may occur in apoplexy, meningitis, hysteria and chorea. It may be used to depress the respiratory spasms of asthmatic attacks. In small doses it may be useful in early stages of hemiplegia and paraplegia. On account of its producing anaesthesia by paralysing the sensory nerve- endings it has been used locally to stop the severe pains of inoperable carcinoma. BRUNNER-ORNSTEIN has recorded gratifying results in obstinate cases of Trigeminal Neuralgia, relief was speedily obtained in half an hour.
ROTTMAN reported on 10 cases of Tabes (Vienna University Clinics) all of whom improved remarkably after treatment with cobra venom. BULLRICH obtained good results in 6 cases of Angina Pectoris and Arteriosclerosis with attacks of Angina, Syphilitic Aortitis with Aortic insufficiency due to coronary sclerosis. In most cases injections of cobra venom were given intramuscularly starting with small doses such as 0.5 to 1 mouse units, twice a week. The relief of pain was appreciable after the third or the fourth dose.
Cytolysin and tissue absorption.–The venom produces necrosis by damaging the intima layer of the blood vessels when it is injected intravenously. The cobra venom has the property of absorbing granulation tissue and neoplastic protective cells formed in the tissues. This property has been utilised in the treatment of malignant growths with the idea of absorbing the neoplastic cells of the tumour. LAIGNEL-LEVASTINE and KOROSSIOS have shown that in this way the growth of the neoplasm is retarded and even distant metastasis may disappear. It cannot be claimed however that a definite cure can thus be brought about.
Haemorrhagin, Thrombose and Agglutinins.–cobra venom when injected intravenously produces intravascular clotting while viper venom and crotaline venom produces excessive haemorrhages. FITZSIMONS (1930) stresses that the pathologic effects of any venom in many vary with the dose injected; while a large dose may be lethal, a small dose may produce a beneficial physiological result.
Small doses of ophidian venom have been used to cure the symptoms produced by the venom itself. The haemorrhagic and neurotoxin principles in it may be used in the treatment of Epilepsy, Blackwater Fever and Haemophilia, etc. Venene, a mixture of different venoms; has been used in the treatment of Menorrhagia, Metrorrhagia, Piles (bleeding), Epistaxis, Purpura, Haemophilia and Flushes in females.
Protein and Histamine desensitization.–It has been pointed out that viper venom produces fall of blood pressure and symptoms of shock from paralysis of the capillaries. The shock produced appears to be similar to that of histamine or protein. It has been suggested that animals protected against histamine may become immune to viper venom, or in other words an anti- histamine serum may act as a prophylactic and curative against viper bite. The venom in graduated doses may be also used to desensitize persons against protein sensitivity.
This has been done in Asthma, or as non-specific protein therapy against Erysipelas, carbuncles, Epilepsy, etc., and it acts by producing protein shock or suppressing allergic symptoms. FRANK COKE observed that persons bitten by honey bees were cured of rheumatic complaints. Cases have also been recorded when persons after a single bite have ceased to get attacks of Epilepsy for years. Similarly bee-venum has been used against rabies since it has been shown to be allied in its action to rabies virus.
