Organophosphates and Carbamates

Question 1

Use of OPs?

Answer 1

pesticides, nerve agents, solvents and plasticizers

Question 2

Exposure routes of OPs

Answer 2

contaminated feed/water
use of empty containers to feed/water animals
lawn treatment
flea treatment or meds
overdosing
intentional poisoning

Question 3

What is storage activation?

Answer 3

if sealed and stored 1-2y, becomes more toxic

Question 4

Toxicokinetics of OPs

Answer 4

lipophilic - readily absorbed through skin, MM, GIT, inhalation
well distributed in body
metabolized in liver
lethal synthesis - liver CYP450 metabolize/bioactivate thiophosphate OPs

Question 5

Chemical properties of OPs

Answer 5

degrade quickly when exposed to environment
subject to storage activation
drug-drug interactions

Question 6

Two types of OPs

Answer 6

thiophosphates and phosphates

Question 7

T/F: thiophosphates are biologically active while phosphates require hepatic bioactivation

Answer 7

false, other way around

Question 8

Major route of elimination of thiophosphates via ______, a serum bound enzyme.

Answer 8

paraoxonase

Question 9

MoA of OPs

Answer 9

Irreversible inhibition of cholinesterases
Primary - muscarinic over-stimulation
Secondary - nicotinic overstimulation (CNS stim)
Tertiary - nicotinic blockade (CNS depression)
Ach increases throughout CNS - overstimulation of nicotinic and muscarinic receptors

Question 10

Muscarinic effects of OPs

Answer 10

overstimulation of PSNS
- DUMBELLS
diarrhea
urination
miosis
bronchospasm
emesis
lacrimation
salivation

Question 11

Nicotinic effects of OPs

Answer 11

Ach accumulation at neuromuscular auction - fasciculations in muscle groups –> depolarization and paralysis
SNS stimulation - sweating, hypertension, tachycardia

Question 12

CNS effects of OPs

Answer 12

crosses BBB
incoordination, depressed motor function, resp depression
impairment of diaphragm + thoracic skeletal m –> resp paralysis
increased pulmonary secretions –> resp failure = usual cause of death

Question 13

Recovery of OP poisoning depends on

Answer 13

generation of new enzyme or Ach-esterase in critical tissues

Question 14

2 delayed effects of thiophosphates

Answer 14

organophosphate-induced delayed polyneuropathy

organophosphate induced intermediate syndrome

Question 15

describe organophosphate induced delayed polyneuropathy

Answer 15

10-14d post exposure
distal degeneration of long motor and sensory axons of peripheral nerves and spinal cord
CS: muscle weakness, ataxia, rear limb paralysis
chickens most sensitive

Question 16

describe organophosphate-induced intermediate syndrome

Answer 16

2-4d after acute effects no longer obvious
symptoms and signs occur after apparent recovery
no muscarinic signs or muscle fasciculations
weakness of resp muscles, neck muscles and proximal limb muscles

Question 17

Lesions expected with OP poisoning

Answer 17

acute death, no specific lesions
pulmonary edema, congestion, cyanosis, hemorrhages, edema in various organs including brain, necrosis of skeletal mm.
degeneration and demyelination of peripheral and spinal motor neurons
pancreatitis reported in some dogs

Question 18

Lab diagnosis of OPs

Answer 18

direct detection in stomach or on skin
may find residues in fat or liver with more lipophilic OPs
plasma ACHesterase activity level
use whole blood

Question 19

Describe the atropine response test

Answer 19

give atropine 1-2mg IV wait 15 ins
if atropine + –> dry skin and MM, increased HR, moderately dilated pupils, low likelihood of OP poisoning
if atropine - –> no signs seen, high likelihood of OP poisoning

Question 20

How do you treat OP poisoning

Answer 20

Decontaminate (wash, induce emus, activated charcoal), support
avoid drugs that depress respiration (opioids) and phenothiazines, ahminoglycosides, muscle relaxants
Atropine as physiologic antagonist
cholinesterase reactivates (oximes)

Question 21

Main concern with OP toxicity is
A) resp failure from excessive airway secretions
B) CNS stimulation resulting in muscle tremors
C) no concern

Answer 21

A - resp failure from airway secretions

Question 22

How does atropine treat OP toxicity?

Answer 22

atropine therapy suppresses or dries pulmonary secretions (remember this was our main concern with OP toxicity because resp failure from excessive secretions)

Question 23

Prognosis of OP toxicity

Answer 23

guided - wide variety in response to treatment

Question 24

Most toxic of the carbamates?

Answer 24

Aldicarb

Question 25

T/F: Carbamates undergo storage activation

Answer 25

false

Question 26

T/F: carbamates require hepatic bioactivation

Answer 26

false

Question 27

MoA of carbamates

Answer 27

Reversible inhibition of acetylcholinesterase (competitive inhibition)

Question 28

Clinical signs of carbamate poisoning

Answer 28

SLUD signs
salivation
lacrimation
urination
diarrhea

Question 29

Death from carbamate toxicity usually due to?

Answer 29

resp failure and hypoxia due to bronchoconstriction leading to tracheobronchial secretion and pulmonary edema

Question 30

Lab Diagnosis of carbamate poisoning?

Answer 30

cholinesterase levels

Question 31

Treatment of carbamates

Answer 31

atropine

Question 32

T/F oximes are effective in treating OP and carbamate toxicity

Answer 32

false , not effective against carbamates