Organophosphorus Poisoning

Acute poisoning by Organophosphorus
compounds is one of the important cause of
morbidity and mortality in the world, especially in
developing countries. Accidental and intentional
pesticides poisoning occurs worldwide with a
significant mortality. Recent studies have shown
an increase in numbers with three hundred
thousand deaths occurring in Asia alone.
The most common pesticide in India are due to
anti-cholinesterase’s which includes
organophosphates and carbamate, followed by
aluminum phosphide.The effective number of
cases of pesticide poisoning occurring in India is
very high, and the calculated number of
intentional cases
as reported by NCRB (National Crime Records
Bureau) is again very high. A retrospective
analysis covering last 15 years showed the most
common agents causing acute poisoning was anticholinesterase’s
followed by aluminum
phosphide.The with a mean age of 27.8
years(range 13 to 82 years)
Organophosphates share structural similarity with
acetylcholine and bind covalently with
cholinesterase molecule. This results in
accumulation of acetylcholine at synapses causing
over stimulation at post-synaptic receptors in
central and peripheral nervous system. The
clinical features of acute OPC poisoning are
secondary to stimulation of muscarinic and
nicotinic acetylcholine receptors in the
parasympathetic system, sympathetic ganglia;
neuromuscular junctions.Disrruption of
transmission will also occur at the acetylcholine
receptor sites within the central nervous system.
The muscarinic receptors,M1 and M2 have
different regional distribution in brain. The M1
receptors are the main type found in the human
cerebral cortex, caudate nucleus, hippocampus,
nucleus accumbens, and globus pallidus,while the
M2 type dominates in the thalamus, brain
stem,pons,and the cerebellum. Different subtypes
of nicotinic receptors have been described in
human brain using ligands with different
affinities. Diagnosis of OPC poisoning is based on history of
exposure to known OP compounds, characteristic
clinical features. Estimation of acetyl
cholinesterase activity is useful for confirmation
of poisoning. But the degree of decrease in
cholinesterase levels does not show linear
relationship with severity of clinical features and
prognosis. Detection of the offending agent in
gastric lavage sample is one of the methods to
determine the involved agent.
OPC poisoning has several toxicological effects
on the body, namely on respiratory system,
cardiovascular system, neurological system &
endocrinal system.The patient is managed on a protocol based
management. The outcome depends on the
severity of toxic sign and symptoms, and the time
lag between poisoning and hospitalization.
Organophosphate poisoning : OP Poisoning
results from exposure to organophosphates (OPs),
which cause the inhibition of acetyl cholinesterase
(AChE), leading to the accumulation
of acetylcholine (ACh) in the body.
Organophosphate poisoning most commonly
results from exposure to insecticides or nerve
agents. OPs are one of the most common causes
of poisoning worldwide, and are frequently
intentionally used in suicides in agrarian areas.
There are around 1 million OP poisonings per
year with several hundred thousand resulting in
fatalities annually.
OP pesticide exposure occurs through inhalation,
ingestion and dermal contact.[ Because OP
pesticides disintegrate quickly in air and light,
they have been considered relatively safe to
consumers. However, OP residues linger on fruits
and vegetables. Certain OP pesticides have been
banned for use on some crops, for example methyl
parathion is banned from use on some crops while
permitted on others. The Environmental Working
Group has developed lists for concerned
consumers, identifying crops with the highest
pesticide residue quantities and the lowest. The
"Dirty Dozen" crops are updated yearly and in
2012 included apples, celery, sweet bell, peppers,
peaches, strawberries, imported nectarines,
grapes, spinach, lettuce, cucumbers, domestic
blueberries and potatoes. Forty-five fruits and
vegetables are listed by the Environmental
Working Group as being regularly found
with pesticide residue associated with OPs.
Example:
 Insecticides including malathion, parathion, di
azinon, fenthion, dichlorvos, chlorpyrifos, ethi
on, trichlorfon.
 Nerve
gases including soman, sarin, tabun, VX
 Herbicides including tribufos [DEF], merphos
are tricresyl phosphate–containing industrial
chemicals. Exposure to any one of the above-listed
organophosphates occurs on a daily basis through
inhalation, absorption, and ingestion, most
commonly of food that has been treated with an
organophosphate herbicide or insecticide.
Exposure to these chemicals can occur at public
buildings, schools, residential areas, and in
agricultural areas. The chemicals chlorpyrifos and
mellathion have been linked to reproductive
effects, neurotoxicity, kidney/liver damage, and
birth defects. Dichlorvos has also been linked to
reproductive effects, neurotoxicity, and
kidney/liver damage, as well as being a possible
carcinogen.Organophosphates inhibit AChE, causing OP
poisoning by phosphorylating the serine hydroxyl
residue on AChE, which inactivates AChE. AChE
is critical for nerve function, so the irreversible
blockage of this enzyme, which causes
acetylcholine accumulation, results in muscle
overstimulation. This causes disturbances across
the cholinergic synapses and can only be
reactivated very slowly, if at
all. Paraoxonase (PON1) is a key enzyme involved in OP pesticides and has been found to
be critical in determining an organism's sensitivity
to OP exposure.