This document summarizes neurotoxicity caused by snake venom. It discusses the main neurotoxic snakes found in India, including cobras, kraits and vipers. The venom contains various proteins like neurotoxins that interfere with neuromuscular transmission. Two main types of neurotoxins are alpha-neurotoxins and beta-neurotoxins. Alpha-neurotoxins bind competitively to nicotinic acetylcholine receptors at the post-synaptic membrane in a reversible manner. Beta-neurotoxins irreversibly bind to the pre-synaptic membrane, depleting synaptic vesicles and impairing neurotransmitter release. Neurotoxicity can cause flaccid paralysis and is a major cause of snakebite mortality

1. NEUROTOXIC SNAKE
VENOM
SCHOOL OF LIFE SCIENCE
(BIOCHEMISTRY)

2. CONTENTS
INTRODUCTION
N
VENOMOUS SNAKES OF INDIA
VENOM :DEFINITION ,APPARATUS ,INGREDIENTS
4
NEUROMUSCULAR TRANSMISSION
NEUROTOXICITY : BETA-NEUROTOXIN
ALPHA-NEUROTOXIN
NNEUROTOXIN DIVERSITY IN SNAKE VENOM
NNCLINICAL MANIFESTATIONS AND TREATMENT
REFERENCES

3. INTRODUCTION
Snakebite is a neglected tropical disease of global importance.
In INDIA , on an average 2,50,000 snake bites are recorded in single year.
Most snake envenomings and fatalities occur in South Asia ,Southeast Asia
and sub-Sahara Africa, with India reporting the most snake bite deaths of any
country.
Neurotoxicity is a well known feature of envenoming due to
Elapidae – Kraits, Cobras, Taipans, Coral snakes
Viperidae – Rattlesnakes, Russell viper, Saw scaled viper
Acute neuromuscular paralysis is the main type of neurotoxicity and is an
important cause of morbidity and mortality related to snakebite..

4. VENOMOUS SNAKES OF INDIA
COBRA
(Naja naja )
Neurotoxic
LD50 : 6-7µg/g
Common krait
(Bungarus caeruleus )
Neurotoxic
.
LD50 : 4-5µg/g
Russell’s viper
(Daboia russelli)
Hemotoxic
LD50 : 5-6µg/g
Saw scaled viper
(Echis carinatus)
Hemotoxic
LD50 :11-12µg/g

5. VENOM
• Simple to complex secretion produced in a specialized gland
that is typically delivered via specialized envenomation
systems, including a secretory gland.
• Snake venoms 90% of dry weight comprises >100 different
protein: enzymes, non-enzymatic polypeptide toxins, and non-
toxic proteins.
• They are used as offensive weapons in immobilizing, killing
. and digesting the preys.
• .
Venom glands of Elapidae & Viperidae
are Situated behind the eye, surrounded
by compressor muscles. The venom duct
opens at the base of the fang, conducting
venom to its tip through a groove or
canal.

6. VENOM COMPONENTS
The major types of biomolecules found in venom can be divided into two groups
1) Enzymatic proteins : phosphodiesterase, hyaluronidase, metalloproteinase ,
phospholipase A2,acetylcholine esterase, etc.
2) Non enzymatic proteins : neurotoxic PLA2, disintegrins, myotoxin.
The potent neurotoxins of snake venom, which are responsible for causing severe
pathophysiological effects after envenomation ,are
 α- neurotoxin
 ĸ-neurotoxins
 Muscarinic
 Fasciculins
 Non conventional
 β- neurotoxin

9. NEUROTOXINS
• Neurotoxins interfere with cholinergic transmission at the synaptic sites of the nerv
ous systems.
• Neurotoxins are generally found in venom of ELAPIDS and VIPERIDS.
• Acts as NEUROMUSCULAR BLOCKING AGENTS (NMBA).
DEPOLARIZING
(dendrotoxins)
NON-DEPOLARIZING
(α-neurotoxins)

10. β-neurotoxins
• Target – PRE-SYNAPTIC TERMINAL
• Mainly involves NEUROTOXIC PLA2
• Monecucco et al have shown that the effects produced by four different sna
ke venom PLA2s (beta bungarotoxin ,taipoxin, notexin and textilo-
• toxin) were similar ,suggesting a similar mechanism of action for pre
synaptic neurotoxins.
• Hydrolysis of phospholipids of pre synaptic membrane and membrane des
tabilization by the products of hydrolysis are likely to be the key driver
s in this process.
• The pre – synaptically active neurotoxins (beta neurotoxins-mostly neur-oto
xic PLA2) bind to the motor nerve terminal, leading to the depletion of syn
aptic Ach vesicles, impaired release of Ach, and later degeneration of the mo
tor nerve terminal.

11. β-Bungarotoxin
• SOURCE - Bungarus multicinctus and B. caeruleus
• LD50 – 0.09 mg/kg (mice)
• Two polypeptide chains: A chain (71 amino acids)
• B chain (60 amino acids)
The binding of beta-Bungarotoxin to the pre synaptic membrane is irreversible.
Pathological change : 3-6h :Depletion of synaptic vesicles
Mitochondrial damage
Degeneration of axons
Denervation complete by 12h
Reinnervation starts at 3 days and complete by 7 days
Clinical effects : Flaccid paralysis by 3h
Return of function by starting by 3days and complete by 7 days
AChE has no effects.
Recovery is dependent upon regeneration of terminal axon.

13. α-neurotoxin
• Alpha neurotoxin (alpha cobratoxin) r
esembles the action of d-tubocurarine (d
TC) and therefore are called curare-mi
mic neurotoxins.
• Belongs to the group of “three finger to
xins”.
Non – depolarizing Post synaptic Block
Target : nAChR
Binding : Reversible (competitive)
α-Bungarotoxin

15. nAChR : Transmembrane allosteric proteins (290kD)
pentamer (α2βγδ)
Each subunit is composed of :
• a large amino-terminal domain;
• four membrane-spanning domains (MI,MII, MIII,MIV)
LIGAND BINDING SITES :α /δ and α/γ or α/ε
Alpha-cobratoxin : Produce a competitive (reversible), non-depolarizing type of
block similar to dTC.
They repetitively associate and dissociate from Ach binding si
tes and therefore, can be reversed by AChEIs.
Alpha Bungarotoxin : Bind almost irreversibly t
o the post synaptic nAChR even though they
produce a non-depolarizing type of block.
Their action is therefore, not reversible by
antivenom or AChE inhibitors.

16. NEUROTOXIN DIVERSITY IN SNAKE VENOM

17. Clinical manifestations

18. TREATMENT
Anti Snake Venom
.
• Antivenom is immunoglobulin purified from plasma of horses or sheep
hyperimmunised with venoms of one (to make monospecific antivenom) or
more (to make poly-specific antivenom) snake species, medically the most
important species in a particular geographical area.
• Indian “polyvalent anti-snake venom serum” (ASV) is raised against
venoms of their “big four” species:
• spectacled cobra (N. naja);
• common krait (B. caeruleus),
• Russell’s viper (D. russelii),
• saw-scaled viper (E. carinatus).

19. Snake Venom Antiserum is a sterile preparation containing
equine immunoglobulin fragments F (ab’) 2.
Freeze dried powder is reconstituted in 10ml of sterile water for
injection I.P. supplied along with the vial.
. Each ml has power to specifically neutralize the venoms of following
species of snakes:
0.60 mg - Indian Cobra (Naja naja) venom
0.45 mg - Common Krait (Bangarus Caeruleus) venom
0.60 mg - Russell’s Viper (Vipera Russelli) venom
0.45 mg - Saw scaled Viper (Echis Carinatus) venom
Reconstituted anti-venom/liquid anti-venom is administered as soon as
possible if clear-cut signs / symptoms of envenomation are evident.
It can be administered in two ways:
• Intravenous injection
• Infusion
All SVA is to be administered over 1 hour.
The patient should be closely monitored for 2 hours.

20. Antivenom Reactions
Anaphylaxis with ASV may be life-threatening. The patient after
ASV administration should be monitored closely and if
anaphylaxis is evident, ASV should be discontinued .
0.5mg of adrenaline must be administered intramuscularly.
Children must be given 0.01mg/kg body weight of adrenaline I/M.
If after 10 to 15 minutes, the patient’s condition has not improved,
or if the condition is worsening, a second dose of 0.5 mg of
adrenaline IM may be given. In the vast majority of cases, no
more doses will be required.
Once the patient has recovered, the antivenom can be restarted
slowly for 10-15 minutes, keeping the patient under close
observation.

21. Manufacturers of ASV in INDIA
• Serum Institute of India , Pune
• Central Research Institute , Kasauli
• Haffkine Biopharmaceutical Co.,Mumbai

22. REFERENCES :
1) Lifan Shih (1999) : Mechanism of the neurotoxin in snake
venom.
2) Udaya K. Ranakawa , David G.Lallo (2013) : Neurotoxicity
in snakebite -The limits of our knowledge.
3) Stephan P. Mackessy (2010) : Venom and toxins of reptiles.
4) Selvanayagam Nirthanan (2003) : Three finger alpha neuro-
toxins and Nicotinic Acetylcholine Receptor.
5)Surjit Singh, Gagandip Singh : Snake bite : Indian Guidelines
and Protocol
6)Priyanka Goswami, Mayuri Samant, Rashmi Srivastava (2014) :
Snake venom, Anti venom and Potential of Snake Venom .

23. THANK YOU
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