Pestcides Flashcards
Action of organophosphate and carbamate compounds
inhibit the enzyme cholinesterase
Acetylcholinesterase (true or red blood cell acetylcholinesterase) is found primarily in________, ________, ____________.
erythrocyte membranes, nervous tissue, and skeletal muscle
Inhibition of cholinesterase leads to_____________
acetylcholine accumulation at nerve synapses and neuromuscular junctions, resulting in overstimulation of acetylcholine receptors.
This initial overstimulation is followed by paralysis of cholinergic synaptic transmission in the CNS, in autonomic ganglia, at parasympathetic and some sympathetic nerve endings (e.g., sweat glands), and in somatic nerves.
Excess acetylcholine results in a _________________ that manifests as a central and peripheral clinical toxidrome
cholinergic crisis
Organophosphate compounds bind ____________ to acetylcholinesterase, thus inactivating the enzyme through the process of phosphorylation
irreversibly
The term ________ describes the permanent, irreversible binding of the organophosphorus compound to the cholinesterase
aging
Once aging occurs, the enzymatic activity of cholinesterase is____________ ______________, and new enzyme must be resynthesized over a period of weeks before clinical symptoms resolve and normal enzymatic function returns
permanently destroyed
Antidotes are more effective if given ________ aging occurs
before
Four clinical syndromes are described following organophosphate exposure:
AICO
acute poisoning
intermediate syndrome
chronic toxicity
organophosphate- induced delayed neuropathy
acute organophosphate poisoning, most poisoned patients are symptomatic within the first _____hours and nearly all within the first _____ hours
8 hours
24 hours
Acute organophosphate poisoning
Symptom onset is most rapid with ________
least rapid with ________
inhalation
transdermal absorption
______________ is the presynaptic neurotransmitter at nicotinic receptors in the sympathetic ganglia and adrenal medulla
Acetylcholine
Acetylcholine is the ______________neurotransmitter at ___________ receptors in the sympathetic ganglia and ____________
presynaptic
nicotinic
adrenal medulla
in the sympathetic ganglia and adrenal medulla, inhibition of acetylcholinesterase at these locations results in sympathetic stimulation, producing ______, _______, _________, _________.
pallor, mydriasis, tachycardia, and hypertension
Nicotinic stimulation at __________ __________ results in
________________, ___________, and _______________.
neuromuscular junctions
muscle fasciculations, cramps, and muscle weakness
An intermediate syndrome occurring ________days after an organophosphate exposure is reported in up to 40% of patients following ingestion.
1 to 5 days
In intermediate syndrome,
Clinical features include _____________________________________________________
paralysis of neck flexor muscles, muscles innervated by the cranial nerves, proximal limb muscles, and respiratory muscles (respiratory support may be needed)
True or false
In intermediate syndrome, symptoms or signs of cholinergic excess are absent
True
In intermediate syndrome, symptoms usually resolve within _____ days
7 days
Chronic toxicity, seen primarily in agricultural workers with daily exposure, manifests as _________________
symmetrical sensorimotor axonopathy
This mixed sensorimotor syndrome may begin with leg cramps and progress to weakness and paralysis, mimicking features of the Guillain-Barré syndrome.
This is characterized by cognitive dysfunction, impaired memory, mood changes, autonomic dysfunction, peripheral neuropathy, and extrapyramidal signs.
Organophosphate-induced delayed neuropathy OPDN
The majority of patients severely poisoned with an organophosphorus insecticide will have the following symptoms:
altered mental status
pinpoint pupils
excessive sweating
difficulty breathing
____________ and ___________ are both quantifiable but serve only as markers of cholinesterase activity at the synaptic junction.
Plasma butyrylcholinesterase
red cell acetylcholinesterase enzyme activity
Red cell acetylcholinesterase is a more accurate indicator of synaptic cholinesterase inhibition, but plasma butyrylcholinesterase is easier to assay and more available.
Death occurs in untreated patients through a combination of __________, ____________, ____________.
bronchorrhea
respiratory muscle paralysis
CNS depression
Immediate priorities following decontamination are
airway protection
provision of ventilation
reduction of bronchorrhea via adequate atropinization
reversal of respiratory muscle paralysis through administration of an oxime
How to do decontamination?
All clothes and accessories must be removed completely, placed in plastic bags, and disposed of as hazardous materials.
The patient should be immediately decontaminated externally with copious amounts of a mild detergent such as dishwashing liquid and water.
Decontamination includes the scalp, hair, fingernails, skin, conjunctivae, and skin folds.
Body fluids should be treated as contaminated.
Abrasion or irritation of the skin should be avoided.
Contaminated runoff water should be contained and disposed of as hazardous material.
Instruments used can be decontaminated using chlorine bleach.
Acute exposure monitoring and airway
Patients with acute exposures should be placed on oxygen, a cardiac monitor, and pulse oximeter.
A 100% nonrebreather mask will optimize oxygenation
This kind of agent should be used when neuromuscular blockade is needed
nondepolarizing
True or false
Succinylcholine is metabolized by plasma butyrylcholinesterase; therefore, prolonged paralysis may result.
True
This is the antidote for significant organophosphate poisonings
Atropine
Action of atropine
As a competitive antagonist of acetylcholine at central and peripheral muscarinic receptors, atropine will reverse the effects secondary to excessive cholinergic stimulation.
Dose of atropine
initial dose of 1.2 to 3.0 milligrams
is given depending on severity of symptoms.
The dose is doubled every 5 minutes until the following are achieved: chest clear on auscultation, heart rate >80 beats/min, and systolic blood pressure >80 mm Hg.
Therapeutic End points in atropine administration
chest clear on auscultation
heart rate >80 beats/min
systolic blood pressure >80 mm Hg
True or false
Pupillary dilatation is not a therapeutic end point
True
True or false
Tachycardia is not a contraindication to the use of atropine in organophosphorus poisoning because tachycardia can occur secondary to bronchospasm or bronchorrhea with hypoxia, which can be reversed with atropine.
True
True or false
atropine reduces respiratory tract secretions but does not reverse muscle weakness
True
T or F
Atropine may prevent or abort seizures (due to cholinergic overstimulation) that occur within the first few minutes of exposure.
True
Minimal exposures may require only decontamination and ________hours of observation in the ED to detect delayed effects.
6 to 8 hours
Reexposure should be avoided because
sequential exposures can result in cumulative toxicity
In significant poisonings, the end point of therapy is determined by
absence of signs and symptoms on withholding of pralidoxime
Most patients respond to pralidoxime therapy with an increase in acetylcholinesterase levels within_______
48 hours
If there is no post-hypoxic brain damage and if the patient is treated early, symptomatic recovery occurs in ____________
10 days
Action of pralidoxime
displace organophosphates from the active site of acetylcholinesterase, thus reactivating the enzyme
reverses muscle paralysis if given early, before aging occurs
It ameliorates muscarinic, nicotinic, and CNS symptoms
Action of Carbamates
transiently and reversibly bind to and inhibit the cholinesterase enzyme.
major difference from organophosphate poisoning, in carbamate poisoning
Regeneration of enzyme activity by dissociation of the carbamate–cholinesterase bond occurs within minutes to a few hours and involves rapid, spontaneous hydrolysis of the carbamate–cholinesterase bond. Therefore, aging does not occur, and restoration of normal function does not require generation of new enzyme.
