EM Toxicology 19: Pesticides - Organophosphates & Carbamates Flashcards
MOA of organophosphates and carbamates
inhibit the enzyme cholinesterase
- acetylcholine accumulates at nerve synapses and neuromuscular junctions, resulting in overstimulation of acetylcholine receptors
Organophosphates bind irreversibly to acetylcholinesterase, thus inactivating the enzyme through the process of phosphorylation - “aging”
examples of organophosphates
high potency:
- parathion
intermediate potency:
- coumaphos
- trichlorfon
malathion
dichlorvos
in organophosphate poisoning symptom onset is most rapid with
inhalation
least rapid with transdermal absorption
clinical effects of cholinergic excess
DUMMBELSSS
Diarrhea
Urination
Miosis
Muscle fasciculation, weakness (including diaphragm)
Bradycardia, Bronchorrhea, Bronchospasm - “KILLER Bs*
Emesis
Lacrimation
Salivation, Sweating
Seizures
Death in organophosphate poisoning is often due to
respiratory failure caused by bronchorrhea and respiratory muscle weakness
remarks on intermediate syndrome of organophosphate poisoning
occurs 1-5 days after exposure
characterized by paralysis of neck flexor muscles, muscles innervated by the cranial nerves, proximal limb muscles, and respiratory muscles
Symptoms or signs of cholinergic excess are absent in this syndrome
remarks on chronic toxicity to organophosphate
This mixed sensorimotor syndrome may begin with leg cramps and progress to weakness and paralysis, mimicking features of Guillain-Barre syndrome
The majority of patients severely poisoned with an organophosphorus insecticide will have:
“DEAD”
Dyspnea
Excessive sweating
Altered mental status
Dot pupils (miosis)
reversal of respiratory muscle paralysis may be achieved through
pralidoxime
Management of organophosphate poisoning
- Protective clothing
- External decontamination
- Monitoring
- 100% oxygen
- Atropine
- Pralidoxime
- Benzodiazepines for seizures
How to administer atropine?
- Initial bolus of 1.2 - 3.0 mg IV (children: 0.05 mg/kg IV)
- Double the dose of IV atropine every 5 mins to achieve adequate atropinization:
- clear chest on auscultation
- HR >80 bpm
- SBP >80 mm Hg - Follow with continuous infusion of 10%-20% per hour of the initial dose of atropine that was required to achieve adequate atropinization
(typical infusion rates vary from 0.4 to 4 mg/hour IV in adults) - Adjust infusion rate to maintain adequate atropnization and avoid atropine toxicity (absent bowel sounds, hyperthermia, delirum)
How to administer pralidoxime?
1.) Give ASAP, may even be given 24-48 hours after exposure
2.) 30 mg/kg IV in adults (30 mg/kg up to 1 gram in children), mixed with normal saline and infused over 5-10 mins
3.) Followed by continuous infusion: 8 mg/kg/hour for 24-48 hours
remarks on oxygen therapy in organophosphate poisoning
A 100% NRM wil optimize oxygenation in the patient with excessive airway secretions and bronchospasm; however, atropine administration should not be delayed or withheld if oxygen is not immediately available.
what to be used as paralytic in intubation
nondepolarizing agent
succinylcholine is metabolized by plasma butyrylcholinesterase; therefore, prolonged paralysis may result
Triggers for treatment with atropine
DED
Dyspnea / respiratory Distress
Excessive sweating and secretions
Dot pupils (miosis)
The dose of atropine is every ______ until the following are achieved: ______
doubled every 5 minutes
clear chest on auscultation
HR >80 bpm
SBP >80 mm Hg
Other remarks on atropine
1.) “Large amounts of atropine, on the order of hundreds of milligrams, may be necessary in massive ingestions”
2.) Pupillary dilatation is not a therapeutic end point
3.) Tachycardia is not a contraindication to atropine because it can occur due to bronchospasm or bronchorrhea with hypoxia, which can be reversed with atropine
4.) Importantly, atropine does not reverse muscle weakness. respiratory support through endotracheal intubation and artificial ventilation is required in severe poisoning
Remarks on pralidoxime
1.) MOA: displaces organophosphates from the active site of acetylcholinesterase, thus reactivating the enzyme
2.) ameliorates muscarinic, nicotinic, and CNS symptoms
3.) IMPORTANTLY, it reverses muscle paralysis if given early, before aging occurs
4.) Pralidoxime is not recommended for asymptomatic patients or for patients with known carbamate exposures presenting with minimal symptoms
examples of carbamates
carbaryl
methomyl
propoxur
trimethacarb
Remarks on carbamates
1.) structurally related to the organophosphate compounds
2.) transiently and reversibly bind to acetylcholinesterase.
- regeneration of enzyme activity by dissociation of the carbamate-cholinesterase bond occurs within minutes to a few hours and involves rapid, spontaneous hydrolysis of teh bond.
- therefore, agingdoes not occur
3.) symptoms are of shorter duration; less central toxicity (seizures does not occur; poor CNS penetration)
management of carbamate poisoning
- ) initial management same as that for organophosphate poisoning
2.) atropine is the antidote of choice
3.) use of pralidoxime is controversial
- the carbamate-binding half-life to cholinesterase is approx. 30 minutes, and irreversible binding does not occur
prognosis in carbamate poisoning
Most patients recover completely within 24 hours
Methomyl poisoning is associated with a high risk of cardiac arrest at presentation as well as subsequent death after resuscitation
Remarks on RBC cholinesterase
ORGANOPHOSPHATE POISONING:
moderate poisoning: typically reduced to 10-20% of normal activity
severe poisoning: <10%
RBC acetylcholinesterase requires regeneration of RBCs to recover, and following a severe exposure, full activity may not be restores for up to 120 days.
CARBAMATE POISONING
Measurement of acetylcholinesterase activity is generally not helpful because enzymatic activity may spontaneously return to normal 4-8 hours after a carbamate exposure
