- Organophosphate compounds are widely used in agricultural sector as PESTICIDES and as chemical war fare.
- Easily accessible ,associate with self poisoning 200,000 /500,00 Mortality associated self-poisoning with pesticides in rural Asia.
- 50-70 % in hospital based study.
- 15-30% in India
- Suicidal rate with OPC 20.6- 56.3%
Irreversibly bind to serine-OH group at the active site of acetylcholinesterase (AChE) à establish covalent bond (phosphorylation)
AGING: loss of alkyl group + strengthening of covalent bond
Phosphorylated AChE is very stable
Inhibition of enzyme activity accumulation of ACh in the synapse and NMJ
Overstimulation of cholinergic receptors
- Paralysis due to organophosphate (OP) poisoning can be three types ?
- It involves acute paralysis secondary to persistent depolarization at the neuromuscular junction caused by persistent stimulation by excessive Ach. Treatment of choice is atropine with or without oximes.
- It is also called as intermediate syndrome.
- It develops 1-4 days after resolution of acute cholinergic symptoms.
- It is manifested as paralysis and respiratory distress.
- It involves proximal muscles with relative sparing of distal muscle groups.
- The pathogenesis presumed to be dysfunction of neuromuscular junction caused by downregulation of presynaptic and postsynaptic nicotinic receptors due to release of excessive Ach and Ca' respectively.
- Atropine is ineffective, symptomatic treatment is given.
- It involves OP-induced delayed polyneuropathy (OPIDN).
- It occurs 1-3 weeks after exposure and is associated with demyelination of axons.
- Delayed onset polyneuropathy after organophosphorous poisoning is seen after a period of 2-4 week
- It is not caused by cholinesterase inhibition but rather by neuropathy target esterase (NTE) inhibition.
- It involves distal muscles with relative sparing of neck muscles, cranial nerves, and proximal muscles.
- Autonomic Nervous System:
- Eye:Miosis, blurred vision, pin point pupil,red tears
- Cardiovascular:Bradycardia, hypotension
- Glands:Extreme salivation, lacrimation, sweating
- Gastrointestinal: Anorexia, nausea, vomiting, diarrhea
- Respiratory: Bronchoconstriction, bronchial secretion
- Skeletal Muscle: Fasciculations, weakness, paralysis
- CNS: Ataxia, confusion, convulsions, coma, paralysis,tremor
- Respiratory depression due to bronchoconstriction,
- Increased secretions,
- Paralysis of diaphragm ,Intercostal muscles and central respiratory depression
MANAGEMENT OF OP:
- Diagnosis is made by Plasma cholinestrase level.
- Reverses muscarinic but not nicotinic
- 2 mg i.v. repeated every 10 mins till signs of full atropinization i.e dilatation of pupils ,tachycardia.
- Pralidoxime (2-PAM)
- Muscarinic signs of OPC poisoning can be remembered as SLUDGE- BBB: Salivation, Lacrimation, Urination, Defecation, Gastric upset, Emesis, Bronchospasm, Blurred vision (Miosis), Bradycardia.
- Delayed onset polyneuropathy after organophosphorous poisoning is seen after a period of 2-4 weeks
- Fatality rate of organophosphorous poisoning in India is 15-30%
- In organophosphorous compound poisoning, organophosphorous compound is a Phosphorylated enzyme Irreversibly inhibit cholinesterase
- Most specific test for organophosphorous poisoning is Plasma cholinestrase level
- Organophosphate inhibits Esteratic site ofAchEs
- Antidote for organophosphorous poisoning is Atropine
Don't Forget to Solve all the previous Year Question asked on OP Poisoning