EM Toxicology 19: Pesticides - Organophosphates & Carbamates

Question 1

MOA of organophosphates and carbamates

Answer 1

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”

Question 2

examples of organophosphates

Answer 2

high potency:
- parathion

intermediate potency:
- coumaphos
- trichlorfon

malathion
dichlorvos

Question 3

in organophosphate poisoning symptom onset is most rapid with

Answer 3

inhalation

least rapid with transdermal absorption

Question 4

clinical effects of cholinergic excess

Answer 4

DUMMBELSSS
Diarrhea
Urination
Miosis
Muscle fasciculation, weakness (including diaphragm)
Bradycardia, Bronchorrhea, Bronchospasm - “KILLER Bs*
Emesis
Lacrimation
Salivation, Sweating
Seizures

Question 5

Death in organophosphate poisoning is often due to

Answer 5

respiratory failure caused by bronchorrhea and respiratory muscle weakness

Question 6

remarks on intermediate syndrome of organophosphate poisoning

Answer 6

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

Question 7

remarks on chronic toxicity to organophosphate

Answer 7

This mixed sensorimotor syndrome may begin with leg cramps and progress to weakness and paralysis, mimicking features of Guillain-Barre syndrome

Question 8

The majority of patients severely poisoned with an organophosphorus insecticide will have:

Answer 8

“DEAD”
Dyspnea
Excessive sweating
Altered mental status
Dot pupils (miosis)

Question 8

reversal of respiratory muscle paralysis may be achieved through

Answer 8

pralidoxime

Question 9

Management of organophosphate poisoning

Answer 9

1. Protective clothing
2. External decontamination
3. Monitoring
4. 100% oxygen
5. Atropine
6. Pralidoxime
7. Benzodiazepines for seizures

Question 10

How to administer atropine?

Answer 10

1. Initial bolus of 1.2 - 3.0 mg IV (children: 0.05 mg/kg IV)
2. Double the dose of IV atropine every 5 mins to achieve adequate atropinization:
   - clear chest on auscultation
   - HR >80 bpm
   - SBP >80 mm Hg
3. 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)
4. Adjust infusion rate to maintain adequate atropnization and avoid atropine toxicity (absent bowel sounds, hyperthermia, delirum)

Question 11

How to administer pralidoxime?

Answer 11

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

Question 12

remarks on oxygen therapy in organophosphate poisoning

Answer 12

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.

Question 13

what to be used as paralytic in intubation

Answer 13

nondepolarizing agent

succinylcholine is metabolized by plasma butyrylcholinesterase; therefore, prolonged paralysis may result

Question 14

Triggers for treatment with atropine

Answer 14

DED
Dyspnea / respiratory Distress
Excessive sweating and secretions
Dot pupils (miosis)

Question 15

The dose of atropine is every ______ until the following are achieved: ______

Answer 15

doubled every 5 minutes

clear chest on auscultation
HR >80 bpm
SBP >80 mm Hg

Question 16

Other remarks on atropine

Answer 16

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

Question 17

Remarks on pralidoxime

Answer 17

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

Question 18

examples of carbamates

Answer 18

carbaryl
methomyl
propoxur
trimethacarb

Question 19

Remarks on carbamates

Answer 19

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)

Question 20

management of carbamate poisoning

Answer 20

1. ) 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

Question 21

prognosis in carbamate poisoning

Answer 21

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

Question 22

Remarks on RBC cholinesterase

Answer 22

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