ORGANOPHOSPHORUS

 OP compounds are widely used as pesticides, especially in

developing countries.
 Nerve agents developed for chemical warfare are derived
from OP insecticides but are much more toxic.
 Physical Appearance
 These compounds are available as dusts, granules or
liquids.
 Some products need to be diluted with water before use,
and some are burnt to make smoke that kills insects.
Toxicokinetics
 Organophosphates are absorbed by any route including
transdermal, transconjunctival, inhalational, across the
GI and GU mucosa and through direct injection.
 Nerve agents
. G agents :- Sarin,Tabun,Soman
. V agents :- VX,VE

Insecticides
Dimethyl compounds Diethyl
compounds
- Dichlorvos - Diazinon
- Fenathion - Parathion-ethyl
- Malathion
 G agents are volatile, are absorbed by inhalation or via
skin
and dissipate rapidly after use.
 V agents are contact poisions unless aerolised, and
contaminate ground for weeks or months.
 The toxicology and management of nerve agent and
pesticide Poisoning are similar.
 Organophosphates are powerful inhibitors of
acetylcholinesterase.
 As a result there is accumulation of acetylcholine in
synapses with continued stimulation of local receptors and
eventual pralysis of nerve or muscle
 Acute Poisoning
1. Cholinergic excess
 Muscuranic effects like Broncho-constriction with
wheezing
and dysponea, cough, pulmonary oedema, vomiting,
diarrhoea ,abdominal cramps, increased salivation ,
lacrimation and sweating , bradycardia, hypotension,
miosis and urinary incontinence.
 Nicotinic effects like fasciculations, weakness,
hypertension, tachycardia and paralysis.
 CNS effects
 Restlessness, headache, tremor, drowsiness, delirium,
slurred speech, ataxia and convulsions.
 Death usually results from respiratory failure
.
 A characteristic kerosene-like odour is often perceptible in
the vicinity of the patient since the solvent used in many
organophosphate insecticides is some petroleum derivative
such as aromax.
 There may be either tachycardia or bradycardia.
 Miosis while being a characteristic feature, may not be
apparent in the early stages. In fact, maydriasis is often
present and hence treatment should not be delayed if there
is absence of pupillary constriction.
 While respiratory failure is the commonest cause of death
other causes may contribute including hypoxia due to
seizures, hyperthermia, renal failure and hepatic failure.
Intermediate Syndrome :-
 Occurs one to four days after poisioning due to long lasting
Cholinesterase inhibition and muscle necrosis , main features
include paralysis characterised by motor cranial nerve palasy .
 It may be due to inadequate treatment of the acute episode
especially involving sub-therapeutic assisted ventilation.
 Intermediate Syndrome have to be managed by supportive
measures, since it does not respond to oximes or atropine.
Delayed Syndrome:-
 Occurs one to four weeks after poisioning due to nerve
demyelination and is characterized by flaccid weakness and
atrophy of distal limb muscles or spasticity and ataxia
 These Syndrome also does not respond to either oximes or
atropine.
 Chronic poisioning:-
 It is usually occurs as an occupational hazard in
agriculturists, especially those who engaged in pesticide
spraying of crops.
 Route of exposure is usually inhalation or contamination
of skin. The following are the main features :-
 Polyneuropathy:-Paraesthesias, muscle cramps, weakness,
gait disorders.
 CNS Effects:-Drowsiness, Confusion, irritability, anxiety,
psychiatric manifestations.
 Depression of Cholinesterase activity
 If the RBC Cholinesterase level is less than 50% of
normal, it indicates organophosphate toxicity.
 Disadvantages:-
 A very low Cholinesterase level does not always correlate
with clinical illness.
 False depression of RBC Cholinesterase level is seen in
perinicious anaemia, hemoglobinopathies, anti- Malarial
treatment.
 Depression of plasma Cholinesterase level is less reliable
indicator of organophosphate toxicity , but is easier to
assay and more commonly done.
 P-Nitrophenol Test:-
 P-Nitrophenol is a metabolite of some organophosphates
and is excreted in the urine .
 Procedure:-
 Steam distilled 10mL of urine and collect the disitillate.
Add sodium hydroxide (2pellates) and heat on a water
bath for 10 minutes.
 Production of yellow colour indicates the presence of P-
NITROPHENOL.
1. Decontamination
2. Antidote administration
3. Supportive measures
4. Prevention of further exposure
 If skin spillage has occured ,it is imperative that the
patient be stripped and washed with soap and water.
 If ocular exposure has occured, copius eye irrigation
should be done with normal Saline or tap water.
 In case of ingestion stomach wash can be done. Activated
charcoal is beneficial.
 Atropine- a competitive antagonist to acetylcholine at the
muscuranic post synaptic membrane and in the CNS, will
block muscuranic manifestations of organophosphate
poisioning.
 Oximes- help to regenerate acetylcholinesterase at
muscuranic, nicotinic, and CNS sites.
 The commonest oxime used in India is PRALIDOXIME.
 Administration of iv fluids to replave the losses.
 Oxygenation/intubation/positive pressure ventilation.
 Following drugs are contraindicated like
parasympathomimitics, phenothiazines, antihistamines,
and opiates.
 After the patient has recovered, he should not be re-
exposed to organophosphates for atleast a few weeks since
he is likely to suffer serious harm from a dose that
normally would be harmless owing to alteration of body
chemistry.
 External
1. Characterstic odur (garliky or kerosene-like)
2. Frothing at mouse and mouth and nose.
3. Cyanosis of extremities
4. Constricted pupils
 Internal
1. Congestion of GI tract:garliky or kerosene-like odur of
contents.
2. Pulmonary and cerebral odema
3. Genaralised visceral congestion.