A SEMINAR ONPHARMACOTHERAPY OF

SNAKE BITE

SUBMITTED BY G . ARUN KUMAR M.PHARM(PHARMACOLOGY)

SUBMITTED TODR. S. NAGARJUNAHODDEPARTMENT OF PHARMACOLOGYRIPER,INDIA-515721.

TOPICS

INTRODUCTION EPIDEMIOLOGY CLASSIFICATION PATHOPHYSIOLOGY MECHANISM OF ACTION SYMPTOMS & SIGNS OF SNAKE-BITE MANAGEMENT OF SNAKE –BITES PREVENTION AND CONTROL

HISTORY They live almost everywhere, in forests, oceans,

streams and lakes. They cannot survive in places where the ground

stays frozen the year around, so they are missing in the polar regions or at high mountain elevations.

Several islands, including Ireland and New Zealand, do not have snakes.

Epidemiology INDIA

Records the highest annual incidence of total snake bites as well as fatal snake bites in the world

2,00,000 bites/year15,000 deaths/year

Rural: urban ratio ---- 9:1 Monsoon and post monsoon season, floods. Out of the 2700 known species of snake only 300

are venomous. Number of Indian snake species:

– 250 [ some say 272]o Venomous species: – 52

Classification of snakes Colubridae

Elapidae

Viperidae

Hydrophidae

Most non venomous snakes eg : grass snake

Cobras, krait, mambas, coral snake

American rattlesnake, Asian pitviper, Russels viper, aders

Sea Snake

Commonest Indian venomous snakes

The big 4 –

1. Common cobra – Naja Naja - neurotoxic venom

2. Common krait – Bungarus Caeruleus - neurotoxic venom

3. Saw scaled viper (carpet viper)– Echis carinatus - haemotoxic Venom

4. Russell’s viper– Daboia russelli - haemotoxic Venom

Commonest Indian venomous snakes – the big 4

The venom is synthesized by the modified salivary glands and injected through special channeled or grooved teeth called fangs

Cobra Krait

Russel’s viper Saw-scaled viper

Poisonous Non poisonous Fangs : hollow

like hypodermic needles

Teeth : 2 long fangs

Tail : compressed

Short and solid

Several small teeth

Not much compressed

Pathophysiology

The local effects of venom serve as a reminder of the potential systemic disruption of organ system function.

Local bleeding - coagulopathies are not uncommon with severe envenomations.

Local edema - increases capillary leak and interstitial fluid in the lungs. Pulmonary mechanics may be altered

Local cell death - increases lactic acid concentration secondary to changes in volume status and requires increased minute ventilation.

The effects of neuromuscular blockade result in poor diaphragmatic excursion.

Cardiac failure can result from hypotension and acidosis.

Myonecrosis raises concerns about myoglobinuria and renal damage.

MECHANISM Hemotoxin (blood toxin) : Hemotoxic venom attacks the

circulatory system and muscle tissue causing excessive scarring,

This venom basically destroys tissue and blood cells. The venom breaks down protein in the region of the bite,

making prey easier to digest.ex : Vipers Neurotoxin (nerve toxin) : Neurotoxic venom attacks the

victim's central nervous system and usually result in heart failure and/or breathing difficulties or even total respiratory paralysis. eg: Cobras,Kraits, Coral Snakes.

Mechanism of Toxicity of Venom The most common types of enzymes are

proteolytic, phospholipases and hyaluronidases

– Proteolytic Enzymes: digestive properties

– Phospholipases: degrade lipids

– Hyaluronidases: speed venom spread through the

body

MECHANISM OF ACTION It takes about 10 minutes for the venom to

affect the nervous system.

Most neurotoxins in snake venoms are too large to cross the blood-brain barrier, and so they usually exert their effects on the peripheral nervous system rather than directly on the brain and spinal cord.

The neurotoxic effects are mainly at the postsynaptic level of the neuromuscular junction where the neurotoxins block acetylcholine receptors, thereby producing muscular paralysis and respiratory failure

Binding of neurotoxin to acetylcholine

NEUROTOXIN SYSTEMIC S&S Neuromuscular junction blockade Muscle paralysis which started from the group of

small sized muscles, larger and then generalized Ptosis respiratory paralysis generalized paralysis double vision (diplopia) sweating, excessive salivation, It takes about 10 minutes for the venom to affect

the nervous system. Mucular weakness sets in 1 hr ,lasts upto 10 days

Neurotoxic symptoms usually resolve in 2-3 days.

SNAKE BITESManagement of

First Aid Methods — Not Recommended

Traditional tight tourniquets. Incisions at the site of snake of bite or any

other place. Local suction either by mouth or by

application of chick. Application of herbal medicines, stones,

seeds, saliva, potassium permanganate solution.

Ingestion of herbal products like oil, ghee, pepper to induce vomiting.

Unnecessary delaying.

Laboratory lnvestigations(depending on clinical features)

Coagulation tests - 20 min whole blood clotting test

ECG Complete blood count Blood urea Urine R/E Serum C P K(creatine phosphokinase) Immuno diagnosis(by ELISA).

SUMMARY MANIFESTATIONS

FEATURE Cobra

Krait

Russels viper

Saw scaled viper

Hump nosed viper

Local pain / tissue damage

YES NO YES YES YES

Ptosis/Neurological signs

YES YES YES NO NO

Hemostatic abn

NO NO YES YES YES

Renal Comp NO NO YES NO YES

Response to Neostigmine

YES NO? NO? NO NO

Response to ASV

YES YES YES YES NO

Neurotoxic

Local reaction

Haemotoxic

COBRA

RV

KRAIT

S HS NV P V

CURRENT THERAPY GUIDELINES

Approach to diagnosis of snake bite The history: • Site of bite, circumstance of bite, time of bite Non-specific symptoms: headache, nausea,

vomiting, abdominal pain, loss of consciousness, difficulty in vision, convulsions. '

Neurological symptoms: Muscle paralysis, difficulty in moving Jaw, tongue and eye, heaviness of eye lids (ptosis), difficulty in swallowing, dribbling of saliva, nasal regurgitation, nasal voice, difficulty in respiration, extreme generalized weakness.

Haematological symptoms: Spontaneous bleeding from gum, vomiting of blood, haemoptysis, haematuria, persistent bleeding from bite site and inflicted wound.

Others: Severe muscle pain, dark colored urine, scanty urine volume, collapse

Treatment protocol Attend to AIRWAY , BREATHING,

CIRCULATION Tetanus toxoid Routine antibiotic is not necessary Identify the snake responsible All patients should be kept under

observation for a min period of 24 hrs. Determine the exact time of bite Pain – give PARACETAMOL Not Aspirin & NSAIDS 5o mg TRAMADOL can also be used

Pharmacotherapy The goals of pharmacotherapy are to neutralize

the toxin, to reduce morbidity and to prevent complications

Antibiotics Immunizations -- Snakes do not harbor

Clostridium tetani in their mouths, but bites may carry other bacteria, especially gram-negative species.

Tetanus prophylaxis recommended if patient not immunized.

Antivenin (At present only polyvalent antivenom is available in our country

INDICATIONS / CRITERIA FOR USING POLYVALENT ANTIVENOM

1. Neurotoxic signs: Ptosis, External ophthalmoplegia Broken neck sign Nasal voice Respiratory difficulty

2. Rapid extension of local swelling (more than half of bitten limb) not due to Green snake bite or tight touriquet.

3. Acute renal failure not due to sea snake bite.4. Cardiovascular abnormalities. 5. Bleeding abnormalities.6. Haemoglobinuria / Myoglobinuria not due to sea

snakes.

ANTISNAKE VENOMASV

AntiSnakevenoms available in India

Polyvalent Snake Antivenom I.P 4 Antivenoms effective against the Big 4, mixed

together Manufacturers:

1. VINS Bioproducts Ltd, AP2. Serum Institute of India Ltd, Pune3. Haffkine Institute, Mumbai4. Bharat Serums of India, Mumbai

Owing to reports of significant bites by pit vipers, there is a move to add a 5th antivenom!

Polyvalent antisnakevenomAdvantages

No need to waste time or effort at identifying the exact nature of venomous snake

Less expensive Easy distribution to

all parts of the country

Disadvantages Decreased efficacy

(?) Increased

incidence of allergic reactions

ASV and children Dose of antivenom Snakes inject the same dose of venom into

children and adults. Children must therefore be given exactly

the same dose of antivenom as adults.

PREVENTION AND CONTROL

Snakes love dark and cool places! Never get into a dark bathroom; first switch on a light

and then see around you before you enter. Drain mesh should be fixed with cement and not with

hinges. In case you need to clean the drain, just break the cement; the cost of a little cement is not worth bartering with your life. Mostly snakes make their way to your bathrooms and toilets through drain system.

Summary Snake bites may be by an non venomous snake

or a dry bite Not all snake bites require ASV ASV is the main stay in the treatment of snake

bites ASV must be initiated if indicated at the

earliest Respiratory paralysis can be because of

different reasons-Neurotoxicity, shock, sepsis, ARF…

MV may be main stay of treatment or just supportive depending on the cause of failure.

REFERENCES

WHO/SEARO GUIDELINES FOR THE CLINICAL MANAGEMENT OF SNAKE BITE IN THE SOUTH EAST ASIAN REGION by David A Warrell-Supplement to The Southeast Asian Journal of Tropical Medicine & Public Health

Visit website www.firstaid.co.in

THANKS FOR THE

ATTENTION!!!!!