0RGANOPHOSPHATE POISONING.

PRESENTER: RHODA MULENGA.

• ORGANOPHOSPHATE POISONING
•  Organophosphorus (OP) insecticides are used widely throughout the world and are
a common cause of poisoning, causing thousands of deaths annually, in the developing
world.
•  Intoxication may follow ingestion, inhalation or dermal absorption.
•  Because some are very lipophilic they may be released from fat depots over a
period of many days.
•  Organophosphorus insecticides inhibit acetylcholinesterase causing accumulation of
acetylcholine at central and peripheral cholinergic nerve endings, including
neuromuscular junction.
•  Many OP insecticides require biotransformation before becoming active and so the
features of intoxication may be delayed.
•  Metabolism occurs by oxidation and hydrolysis by esterases and by reaction with
glutathione.
•  Elimination of OP is mostly in the urine and lesser amounts in feces and expired air.
• PATHOPHYSIOLOGY
•  OP insecticides form an irreversible bone with acetylcholinesterase (the enzyme
responsible for the breakdown of acetylcholine).
•  When this enzyme is inhibited there is an accumulation of acetylcholine at central
as well as peripheral cholinergic nerve endings.
•  This results in overstimulation of both muscarinic and nicotinic receptors resulting
in the signs and symptoms seen.
•  Recall that:
•  Acetylcholine is found in autonomic ganglia (both sympathetic and parasympathetic
ganglia)
•  Terminal postganglionic parasympathetic nerves fibers at the motor endplates of
nerves in skeletal muscle as well as some cranial nerves innervating visceral contain
acetylcholine
•  Both muscarinic and nicotinic receptors are widely distributed in the central nervous
system as well as all over the body.
• CLINICAL FEATURES
•  Poisoning is characterized by:
•  Anxiety
•  Restlessness
•  Tiredness
•  Headache
•  Muscarinic (cholinergic) features such as nausea, vomiting, abdominal colic, diarrhea, tenesmus, sweating, hypersalivation
and chest tightness. Miosis may be present.
•  Nicotinic effects include muscle fasciculation and flaccid paresis of limb muscles, respiratory muscles and occasionally of
extraocular muscles.
•  Respiratory failure will ensue in severe cases and is exacerbated by development of brochorrhea and pulmonary edema.
•  The intermediate symptoms usually become established 2-4 days after exposure when the symptoms and signs of the
acute
• cholinergic syndrome are no longer obvious.
•  The characteristic features of the syndrome are weakness of muscles of respiration (Diaphragm, intercostal muscle and
accessory muscle including neck muscle) and of proximal muscle.
•  Accompanying features often include weakness of muscles innervated by some cranial nerves.
•  Delayed polyneuropathy is a rare complication of acute exposure to some OP insecticides not marketed in most countries.
It is initiated by phosphorylation and subsequent aging of at least 70% of neuropathy target esterase (NTE) in peripheral
• DIAGNOSIS
•  This is confirmed by measuring the erythrocyte cholinesterase
activity.
•  This may be decreased to 30-50% in asymptomatic patients, 10-
20% in moderate poisoning and <10% in severe poisoning
•  Plasma cholinesterase activity is less specific but may also be
depressed.
•  Other investigations include:
•  Urea and electrolytes to rule out electrolyte disturbances
•  Stool for microscopy, culture and sensitivity to rule out
gastroenteritis.
• TREATMENT
•  ABCs (Resuscitation)
•  Mild cases require no specific treatment other than the removal
of soiled clothing.
•  Atropine 2mg IV should be given every 3-5 min if necessary to
reduce increased secretions, rhinorrhea and bronchorrhea.
•  Symptomatic patients should be give an oxime (pralidoxime,
obidoxime or HI-6) to reactivate inhibited acetylcholinesterase.
•  Pralidoxime chloride 30mg/kg by slow IV injection followed