Organophosphate poisoning Basis of organophosphate poisoning Clinical features Treatment
Organophosphates What are Organophosphates? group of potent nerve agents, functioning by inhibiting the enzyme acetyl cholinesterase Examples :-
Mechanism of organophosphate poisoning Organophosphates inactivate AChE by phosphorylating the serine hydroxyl group located at the active site of AChE. The phosphorylation occurs by loss of an organophosphate leaving group and establishment of a covalent bond with AChE.
Mechanism of organophosphate poisoning
increase and accumulation of acetylcholine at nerve endings, stimulating neuro- effecter junctions, skeletal neuro- muscular junctions, autonomic ganglia and in the brain. AChaccumulates throughout the nervous system, resulting in overstimulation of muscarinic and nicotinic receptors Overstimulation causes a depolarising block of neuromuscular junction receptors.
Mechanism of organophosphate poisoning Acetyl cholinesterase Acetyl choline Depolarizing Block
Muscarinic effects by organ systems include the following: Cardiovascular- Bradycardia, hypotension Respiratory - Rhinorrhea, bronchorrhea, bronchospasm, cough, severe respiratory distress Gastrointestinal - Hypersalivation, nausea and vomiting, abdominal pain, diarrhea. Genitourinary - Incontinence Ocular - Blurred vision, miosis Glands - Increased lacrimation, diaphoresis
Nicotinic signs and symptoms muscle fasciculations, cramping, weakness, and diaphragmatic failure. CNS effects anxiety, emotional liability, restlessness, confusion, ataxia, tremors, seizures, and coma.
Poisoning may follow ingestion, inhalation or dermal absorption At first Person feels sick Complains of headache General weakness or tiredness Then Person begins to sweat and salivate, may vomit and diarrhea stomach cramps Pupils (of the eyes) become very small
Blurred vision Muscle twitch and hand shake Breathing becomes bubbly Person has a fit and unconscious
Treatment Atropine block muscarinic effects due to excessive acetylcholine 0.6-2 mg should be given to reduce bronchorrhoea and rhinorrhoea, together with an oxime, such as pralidoxime
Pralidoxime (2-PAM) Nucleophilic agent that reactivates the phosphorylatedAChE by binding to the OP molecule not effective once the OP compound has bound AChEirreversibly Recommendation - administration within 48 h of OP poisoning Administered by slow injection or as an infusion.