Pesticides are chemicals that are used to kill pests such as bacteria, insects, snails, rats and so on. ... Insecticides are a type of pesticide that is used to specifically target and kill insects.
Organophosphates are the major components present in most insecticides. It acts by inhibiting acetylcholinesterase, the enzyme that breaks down acetylcholine. As excess acetylcholine is not cleared up from the site of release and action, there is overstimulation of the acetylcholine receptors. This leads to excess action of the acetylcholine molecule eventually leading to cholinergic crisis.
Nerve agents used in chemical warfare contain a more potent and toxic form of Organophosphates.
Acetylcholine is a neurotransmitter released from parasympathetic nerve endings. The actions of acetylcholine depends on their site of action and receptors. The acetylcholine receptors are classified as Nicotinic and Muscarinic receptors.
The Nicotinic receptors are named so because the stimulation of these receptors by acetylcholine leads to effects similar to actions of nicotine.
Muscarine is a toxin present in a specific type of poisonous mushrooms known as toadstools. The muscarinic receptors are named so because, in smooth muscles and glands, the stimulation of these receptors by muscarine leads to effects similar to stimulation by acetylcholine.
Acetylcholine is the chief neurotransmitter released from parasympathetic nerve endings. Once released, it binds to specific receptors on the target organs. Upon binding, it stimulates the receptors leading to the receptor and location specific actions of acetylcholine.
Acetylcholinesterase(AChE) is the molecule that helps break down acetylcholine(ACh), thus preventing overstimulation of acetylcholine receptors. Also, by cleaving the acetylcholine molecule, AChE aids its reuptake by the nerve cells.
Organophosphates act by inhibiting the enzyme acetylcholinesterase. Due to this inhibition, acetylcholine released from nerve terminals is not broken down, therefore not reuptaken. The excess acetylcholine causes over stimulation of the acetylcholine receptors, both nicotinic and muscarinic. With prolonged untreated exposure, this can lead to cholinergic crisis.
The effects of organophosphate poisoning can be understood by first studying the nicotinic and muscarinic effects of acetylcholine.
The nicotinic effects of acetylcholine are as follows:
Receptor
|
Target/
Location
|
RESPONSE
|
NM
|
Neuromuscular Junction @ skeletal muscle
|
Skeletal muscle contraction
|
NN
|
Autonomic ganglia,
CNS, and
Adrenal medulla
|
Ganglionic
transmission
CNS
excitation
Release
of adrenaline
|
The muscarinic effects of acetylcholine are summarised below:
Target/
Location
|
Receptor
|
RESPONSE
|
Eyes
|
M3
M3
|
Contraction of iris sphincter muscle - Constriction of pupil – Miosis
Contraction of ciliary muscle
– Accommodation for near vision |
Heart
|
M2
M2
|
↓Heart
rate
↓Conduction
velocity
No effects on ventricles, Purkinje system
|
Lungs
|
M3
M3
|
Contraction – Bronchospasm
Secretion
|
G.I.tract
|
M3
|
↑Motility-cramps
Secretion
Contraction-diarrhea, involuntary defecation
|
Bladder
|
M3
M3
|
Contraction of detrusor muscle
Relaxation of trigone/sphincter
|
Sphincters
|
M3
|
Relaxation,
except lower esophageal, which contracts
|
Glands
|
M3
|
Secretions including sweat(thermoregulatory),
salivation,
and lacrimation.
|
Blood vessels
(endothelium)
|
M3
|
Dilation (via NO/endothelium-derived relaxing factor) –
no parasympathetic
innervations,
no effects of indirect agonists
|
In organophosphate(OP) poisoning, inhibition of AChE leads to accumulation of ACh and overstimulation of its receptors. The symptoms and signs of OP poisoning are due to excess action of Acetylcholine.
The effects of OP poisoning is described below with relation to the receptors involved:
Type of receptor
|
Receptor sub-type
|
Target location
|
Effects
|
Nicotinic
receptor stimulation
|
NM
|
Neuromuscular junction
|
Weakness,
fasciculations,
cramps, paralysis
|
NN
|
Autonomic ganglia
|
Tachycardia, hypertension
|
|
Adrenal medulla
|
Adrenaline mediated effects such as tachycardia,
hypertension
|
||
CNS
|
Anxiety, restlessness, ataxia, convulsions, insomnia,
dysarthria, tremors, coma, respiratory depression, circulatory collapse
|
Type of receptor
|
Receptor sub-type
|
Target location
|
Effects
|
Muscarinic receptor
stimulation
|
M1 – M5
|
CNS
|
Anxiety, restlessness, ataxia,
convulsions, insomnia, dysarthria, tremors, coma, respiratory depression,
circulatory collapse
|
M2
|
Heart
|
Bradycardia, Hypotension
|
|
M3
|
Iris sphincter
(Pupillary sphincter),
Ciliary muscle
|
Miosis (constriction of pupil)
Blurred vision
|
|
M3
|
Exocrine glands
|
Rhinorrhea, Bronchorrhea
Increased salivation &
lacrimation
Excessive sweating
Diarrhea
|
|
M3
|
Smooth muscles
|
Bronchospasm
Abdominal pain
Urinary incontinence
|
Treatment of OP poisoning:
1. Immediate measures such as termination of exposure, personal protection of person attending the patient and decontamination of the affected patient.
2. General supportive measures such as maintenance
of a patent airway, including endobronchial aspiration; administration of oxygen; artificial
respiration, if required; alleviation of
persistent convulsions with diazepam; and treatment of shock.
3. The muscarinic effects of OP poisoning can be countered using the anticholinergic drug, ATROPINE. It acts by blocking the muscarinic acetylcholine receptors as a competitive antagonist. Atropine in sufficient dosage effectively antagonizes
the actions of acetylcholine at muscarinic receptor sites. In order to alleviate the CNS manifestations, atropine should be given in larger doses to cross the blood–
brain barrier.
4. The chief mechanism involved in OP poisoning is the inhibition of the enzyme acetylcholinesterase (AChE). The drug PRALIDOXIME, a cholinesterase reactivator, reactivates acetylcholinesterase, thus treating the primary mechanism of OP poisoning.
References:
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