Organophosphate poisoning is caused by exposure to pesticides, herbicides, and nerve gases. It results in the inhibition of acetylcholinesterase, leading to accumulation of acetylcholine and overstimulation of muscarinic and nicotinic receptors. Symptoms range from mild like nausea to severe like respiratory failure. Treatment involves atropine to block acetylcholine receptors, oximes like pralidoxime to reactivate inhibited acetylcholinesterase, diazepam for seizures, supportive care, and monitoring for complications like pneumonia. Prognosis depends on prompt treatment and severity of exposure.

1. Organophosphate poisoning
Chitra gayen
Final year npcc

2. Introduction
Organophosphorus compounds are used as pesticides, herbicides, and
chemical warfare agents in the form of nerve gases. Acute poisoning by
these agents is a major global clinical problem, with thousands of deaths
occuring every year.

3. Classification

6. Pharmacokinetics
● Most organophosphates are highly lipid soluble compounds and are well absorbed from
intact skin, oral mucous membranes, conjunctiva and the gastrointestinal and respiratory
tracts.
● They are rapidly redistributed to all body tissues.
● The highest concentrations are found in the liver and kidneys.
● This high lipid solubility means that they easily cross the blood/brain barrier and therefore
produce potent effects on the CNS.
● Metabolism occurs principally by oxidation in the liver with conjugation and esterase
hydrolysis producing a half-life of minutes - hours.
● The oxidative metabolites of malathion and parathion (malaoxon and paraoxon) are active
forms and are subsequently hydrolyzed into inactive metabolites.
● Elimination of organophosphorus compounds and its metabolites occur mainly via urine,
bile and faeces.

7. Mechanism of action
OP Inactivate AcetylCholinesterase (Ach E).
Establishment Of A Covalent Bond With AchE.
" Ach E Is An Enzyme That Degrades The Neurotransmitter Acetylcholine (Ach) Into Choline
And Acetic Acid.
○ Ach Is Found In CNS & PNS, Neuromuscular
Junctions, And Red Blood Cells (RBCS).
○ Once Ach E - Inactivated, Ach Accumulates Throughout The Nervous System Overstimulation Of
Muscarinic And Nicotinic receptors.

8. ○ Once an organophosphate binds to AChE, the enzyme can undergo one of the
following.
○ Endogenous hydrolysis of the phosphorylated enzyme by esterases or
paraoxonases
○ Reactivation by a strong nucleophile such as pralidoxime (2-PAM)
○ Irreversible binding and permanent enzyme inactivation (aging)
The onset and severity of symptoms depend on the specific compound,
amount, route of exposure, and rate of metabolic degradation.

10. Four varieties of neurotoxic effects have been observed.
o Type -1(acute cholinergic effect) paralysis (24-48 hours): patient presents with giddiness,
restlessness, anxiety, headache, fasciculations, twitching, slurred speech,
mental confusion and ataxia (failure of muscular coordination).
o Type – II paralysis: (intermediate syndrome, 24-96 hours: characterized
by muscle weakness, respiratory insufficiency, absence of deep tendon
Reflexes.
o Delayed polyneuropathy (2-3 weeks) The neuropathy in Organophosphorous Induced Delayed Poly Neuropathy
(OPIDP) is typically a symmetrical sensory-motor neuropathy, with a distal
predominance. Initial symptoms are paresthesia in the lower limbs and pain in
the calves, followed by motor involvement of the lower limbs, manifested by leg
weakness, foot drop and muscle hypotonia.
o Guillain-barre syndrome

11. Symptoms and signs of organophosphate poisoning based on receptors involved

12. Symptoms and signs of organophosphate poisoning based on time of manifestation

14. DIAGNOSTIC TESTING:
The essential finding in laboratory diagnosis is depression of the cholinesterase activity.
However, the diagnosis of OP poisoning is usually confirmed retrospectively, as the majority of facilities
cannot perform these tests on an immediate basis.
Mild poisoning - 20-50% of normal cholinesterase level
Moderate poisoning - 10-20% of normal cholinesterase level
Severe poisoning - < 10% of normal cholinesterase level
Blood: HB, TC, DC, ESR, Urea, Creatinine, Sugar / RBS
Urine: albumin, sugar, microscope
E.C.G. Serum electrolytes – especially Na + and K +Arterial blood gas studies
Chest X-ray Sputum for culture and sensitivity Serum pseudocholinesterase levels on first day and alternate
days to know the prognosis.

15. Management of OP poisoning -
1. Prevention of absorption
a. Decontamination
b. Gastric lavage
c. Adsorbent
d. Bowel wash
e. Ryle’s tube aspiration
2. Supportive measures:
a. Proper suctioning
b. Establishing respiration
c. Maintaining circulation
3. Specific therapy
a. Atropine/ glycopyrrolate
b. Oximes

16. Atropine:
Mechanism:
1) It binds with synaptic receptors replacing acetyl choline
2) It also decreases acetyl choline production at nerve terminals.
Dose: 2-5 mg IV slowly stat
This dose can be doubled every 20-30 min, until signs of atropinization occur.
In severe poisoning continuous infusion 0.02-0.08 mg/kg/nr is preferred.
Does of atropine should be sufficient to produce signs of atropinization.
Studies have shown that there is no decrease in mortality or increased prognosis
by giving large dose.
The highest does given in Indian literature is 310mg.

17. Signs of atropinization:
1. Dilatation of pupil
2. Tachycardia
3. Flushing
4. Dry skin/mouth
5. Increased temperature
Adverse effects:
Dry hot skin Hallucination (psychosis)
Dry mouth Tremors
Flushing Convulsions
Tachycardia Coma and collapse
Limitation of atropine: It has no effect on
nicotinic receptors. In the presence of
cyanosis, it may precipitate ventricular
fibrillation. Therefore Once controlled,
atropine
should be tapered and stopped keeping the
pupil dilated for a week.

18. Glycopyrrolate (glycopyrronium bromide):
It is a newer anticholinergic drug now-a-days used for organophosphorus compound
poisoning. It is a quaternary ammonium compound. The does is usually titrated with
clinical signs and symptoms.
Oximes (enzyme reactivators):
In 1951 and 1953 wilson and gimsburg introduced a new class of compound known as
hydroxylamine’s. These compounds are capable of reactivating phosphorylated
enzyme. With the discovery of these hydroxylamines, new compounds followed. They
are:
PAM – pyridine – 2 aldoxime methyl chloride
DAM-diacetyl monoxime – 1-2 gms IV slowly (200mg/min)
Obidoxime chloride – IV 3-6mg/kg does can be repeated every 20 minutes.

19. Mechanism of action:
Reactivates the organophosphorus inhibited acetyl cholinesterase by combining with phosphorus group and
forming a soluble complex.
Prevents / protects additional acetylcholinesterase from further
phosphorylation.
Direct action on neuromuscular junction which is in a depolarized state.
Large doses can inhibit Ach esterase.
Toxicity of oximes: adverse effects generally occur at plasma level of > 400 µg/mL.
Local irritation, drowsiness, giddiness, blurred vision, diplopia. Tachycardia and
Hypotension.
Dose: 1-2 gms IV slowly-stat.
This does can be repeated after 6-12 hrs.
Titration of this does is based on clinical response.
In severe poisoning, continuous infusion is given at a rate of 500mg/hr after a
bolus does
Maximum 12gms / 24 hrs.

20. Mild -Nausea, malaise, fatigue, minimal muscleweakness cramping without diarrhea
Treatment -Remove from exposure until cholinesterase
returns to 75% of base line.
Moderate -SLUDGE and /or tremors, weakness, fasciculations, confusion, lethargy, anxiety & bronchorrhea
Administer atropine until bronchial secretions clear + PAM 1g q4-6 or infusion for minimum of 24-48 hrs. or
longer until signs and symptoms resolve.
Severe SLUDGE, respiratory insufficiency, weakness, fasciculations, coma paralysis, seizures and autonomic
dysfunction.
Administer atropine until bronchial secretions clear (may require repetitive dosing) + PAM as infusion + diazepam
for seizures. Continue PAM until all signs and symptoms resolve, for at least
24-48 hours. Consider longer therapy for fat�soluble agents or others as defined by EMG.

21. Others-
Diazepam:
The addition of diazepam to atropine and PAM Improves survival. Diazepam decreases
cardiac and brain morphologic damage resulting from organophosphate induced
Seizures. 5-10 mg/iv repeat every 5-10 minutes upto 30 mg.
Clonidine:
Clonidine inhibits the release of Ach from central and peripheral cholinergic neurons.
Clonidine pretreatment at 0.3 mg/kg increased the onset latency to tremor, onset
latency to death and percentage of survivors in one study. It is suggested that the
central cholinergic neurons involved in regulation of respiration and fine motor control
but not peripheral motor neurons are inhibited by the action of clonidine on alpha�receptors.

22. Antibiotics:
Since these patients are vulnerable to infections, antibiotics are started:
Broad spectrum antibiotics are started initially.
Aminoglycosides – (Note for renal function)
Based on culture and sensitivity appropriate antibiotics to be started.

23. Drugs contraindicated in organophosphorus poisoning
1. Morphine: depresses the respiratory centre and decreases the sensitivity of
PCO2 Decreased levels of consciousness Nausea and vomiting Decreases blood pressure
It can aggravate signs and symptoms
Morphine causes intense miosis masking the prognosis or signs of atropinization.
2. Theophylline: Theophylline causes bronchial smooth muscles to relax and
decreases cyclic AMP levels through the enzyme adenylate cyclase.
This enzyme is also responsible for breakdown of vesicles to release acetylcholine
which can aggravate the condition.
Aminophylline … decreases blood pressure can cause arrhythmias.
4. Succinylcholine – decreased pseudocholinesterase levels can prolong the
duration of action.
5. Phenothiazines

24. COMPLICATIONS:
1. Seizures: Diazepam 5-10 mg IV slowly (0.25mg/kg/IV) repeated after 10-15
mins. Phenytoin 15-20 mg/kg IV slowly stat and repeat after 6-8 hours.
2. Pulmonary edema ; increased atropine, diuretics, 100% O2 with PEEP 5-10 cms
3. Paralytic ileus: Correct hypokalemia
4. chemical pneumonitis
5. Bronchopneumonia
6. electrolyte imbalances
7. Acid base disturbances
8. ARDS: Diagnosed by chest x-ray; increased hypoxia not responding to increased FiO2.