Organophosphate poisoning

Organophosphate poisoning

Dr. Shamil AL-Nuaimi

pest is any harmful, destructive, or troublesome animal, plant or microorganism.”

“…a pesticide is any substance or mixture of substances intended for preventing, destroying, repelling, or mitigating any pest.”
Definition of Pesticide

Acute pesticide poisoning is an important cause of worldwide morbidity and mortality.

Ninety-five percent of fatal pesticide poisonings occur in developing countries. Serious cases of pesticide poisoning are more likely to occur in adults than in children.

About three-quarters of the pesticide fatalities were due to suicide.

Exposure

Home Exposure

• Accidental ingestion
• Lawn and garden use
• Insect control
• Food supply
• Water supply


Occupational Exposure
• Farms & Farm worker
• Pesticide applicator
• Manufacture
• Mixing and handling
• Landscapers

Other Exposure

•Dietary exposure
•Pesticide residues on crops
•Community exposure
•Airborne drift from commercial app
•Contaminated drinking water
•Leaching from soils to ground water

Organophosphate compounds produce muscle weakness by three different mechanisms:

The first occurs during the cholinergic phase.

Fasciculation progress to paralysis due to depolarization and desensitization blocks at the on neuromuscular junction
MECHANISM OF ACTION


During the second or intermediate phase excessive entry of calcium ions into the muscle due to prolonged transmitter receptor interaction probably produces muscle necrosis.

Finally, muscle weakness may be due to demyelination of nerves.

This begins 2 to 3 weeks after intoxication and spares the muscle of respiration.

Acute Effects

Cholinergic Features

The cholinergic effects of organophosphate poisoning depend on the balance between muscarinic and nicotinic receptors
The mnemonic DUMBELS describes signs of cholinergic excess.

Clinical Presentation

DUMBELS (diaphoresis and diarrhea; urination; miosis; bradycardia, bronchospasm, emesis; excess lacrimation; and salivation).


Intermediate Syndrome

Occurs after resolution of acute cholinergic crisis.

24-96 hours after exposure.

Characteristics:-acute respiratory paresis, muscular weakness

(facial, neck and proximal limb muscles).

Cranial nerve palsies and depressed tendon reflexes (often)

Lacks muscarinic symptomatology. Result of pre-and postsynaptic
dysfunction of neuromuscular transmission.

Compounds involved are methyl parathion, fenthion and

dimethoate.

(Organophosphate-induced delayed neuropathy)

Damage to afferent fibers of peripheral and central nerves and


Inhibition of “neuropathy target esterase” (NTE).
Certain OPs rarely cause this kind of neurotoxicity.

Manifests as weakness or paralysis and paresthesia of the

extremities. Predominantly legs. May persists for weeks to years.

Suggested diagnostic criteria for the organophosphate-induced delayed syndrome include the following:

1. A history of severe acute organophosphate poisoning about 1 to 6 weeks prior to the onset.
. 2. Symptoms and signs of polyneuropathy and later with or without concurrent pyramidal signs.
. 3.Denervation changes shown by electromyography.
. 4.Slow recover.
. 5.Reasonable exclusion of other nervous disease
Chronic Effects

Skin decontamination

Gastrointestinal decontamination

Pulmonary ventilation

Cardiopulmonary monitoring

Treatment

Aging:- As time progresses with OP binding to AChE, it’s phosphoryl bond is strengthened by loss of one alkyl group from phosphoryl adduct.

(Pralidoxime use therefore is limited after a couple of

days).

Atropine noncompetitively antagonizes both muscarinic and CNS effects of organophosphate poisoning

Atropine has no effect on muscle weakness or respiratory failure in severe poisoning, since this drug does not reactivate the cholinesterase enzymes.
ANTIDOTES

For a therapeutic intravenous dose in symptomatic patients, use 2 to 4 mg in adults or 0.015 to 0.05 mg/kg in children every 15 minutes as needed.

The administration of atropine as an antidote does not require confirmation by acetylcholinesterase levels.

The drying of secretions or full atropinization, rather than dilated pupils, is the effective endpoint of atropine titration.

Do not wait for the return of cholinesterase levels before treating significantly symptomatic patients with atropine.


Alternate routes for atropine administration (when rapid intravenous access cannot be achieved) may induce the intraosseous route in children, and nebulized atropine by inhalation in adults.

Therapy with 2PAM should be continued for at least 18 hours or longer, depending on the patient's clinical status and the properties of the suspected toxin.

In a severely poisoned adult the dosage of pralidoxime (e.g., 500 mg/hour) should be continuously maintained until clear and irreversible clinical improvement is achieved. This may take days until residual insecticide is cleared from body stores
Pralidoxime (2PAM)

If severely dyspneic give 4 to 6 mg atropine plus 2PAMCl 1 g IV. Watch heart rate, blood pressure

If moderate exposure to vapor (respiratory distress, gastrointestinal signs and symptoms, muscle twitching): give 6 mg atropine and 2PAMCl. Always give diazepam (10 mg IM)
Cautions

Seizures often respond to atropine and 2PAM. If they do not, give diazepam.

Watch for worsening of respiratory depression
Observe for recurrence of nicotinic symptoms. If they do not recur for the next 24 hours, discontinue therapy.

Weaning the patient off should be performed by set increments (e.g., 25% every 8 hours). Watch the patient for at least 1 hour after each adjustment.

1.Avoid parasympathomimetic agents (physostigmine, succinylcholine) because they may potentiate anticholinesterase activity
2.Phenothiazines and antihistamines have anticholinesterase activity
3.Central nervous system depressants (e.g., opiates)


During antidote administration, the patient should be followed closely for signs of respiratory failure and atropinization

Full recovery generally occurs within 10 days when optimum treatment is quickly instituted.

Persistent CNS effects and peripheral neuropathies have been reported in a few survivors.

The patient must avoid reexposure until cholinesterase activity is over 75% of normal survivors
Prognosis