Organophosphates & Carbamates

Question 1

Where are organophosphates naturally occurring?

Answer 1

Associated with DNA, RNA, and many cofactors that are essential for life

Question 2

Organophosphates will irreversibly inactivate __________

Answer 2

acetylcholinesterase

*meaning the animal will have persistent Ach activity

Question 3

Organophosphates are subject to storage activation, what does that mean?

Answer 3

If sealed and stored for 1-2 years, it can become more toxic

*impurities will cause these compounds to be more toxic

Question 4

Thiophosphate OPs are more or less lipid soluble than phosphate OPs?

Answer 4

MORE lipid soluble

Question 5

What are the most common means of OP toxicosis in animals?

Answer 5

**since these compounds are lipophilic they are readily absorbed through the skin and mm, GIT, and inhalation

*dermal, oral, inhaled

Question 6

Where do OPs distribute in the body?

Answer 6

usually well distributed throughout the body in most cells, including the CNS

Question 7

Where are OPs metabolized?

Answer 7

In the liver - excretion and bioactivation take place

*LETHAL SYNTHESIS - CYP450 liver enzymes metabolize or bioactivate thiophosphate OPs

Question 8

What OPs will undergo lethal synthesis in the liver?

Answer 8

Thiophosphate OPs

Question 9

What changes will occur in the body of an animal that is chronically exposed to OPs?

Answer 9

• continued exposure can lead to adaptation to decrease acetylchoinesterase
• enzyme induction or increased acetylecholinesterase (make more enzyme that is being inhibited)

OR

-receptor down regulation or decrease in acetylcholine (decrease the amount of receptors)

Question 10

There are two types of Organophosphates:

1. _________ : these are biologically active
2. __________: these require liver metabolism to become active (lethal synthesis)

Answer 10

1. phosphates

2. Thiophosphates

Question 11

What is the major route of elimination of thiophosphates?

Answer 11

paraoxonase - a serum bound enzyme

Question 12

Thiophosphates are rapidly absorbed by what tissue?

Answer 12

Adipose tissue (lipid soluble)

*a slow release from fat may lead to delayed or prolonged cholinesterase inhibition

Question 13

What are the 3 consequences of OPs irreversible inhibition of cholinesterases?

Answer 13

1. Muscarinic receptor over stimulation
2. Nicotinic receptor over stimulation (CNS stimulation - muscle fasiculations)
3. Nicotinc blockade (CNS depression - paralysis)

Occurs in that order

Question 14

What signs would you expect to see in a patient with over stimulation of muscarinic receptors?

Answer 14

= over stimulation of the parasympathetic

DUMBELLS

dhr, urination, miosis, bronchospasm, emesis, lacrimation, salivation

**patients will usually die due to increased pulmonary secretions coupled with respiratory failure (nicotinic blockade)

Question 15

what animals are most sensitive to organophosphate-induced delayed polyneuropathy?

Answer 15

Chickens

*this occurs 12-14 days post exposure

muscle weakness, ataxia, rear limb paralysis

Question 16

What is the time frame of development of OP-induced intermediate syndrome?

Answer 16

Occurs 2-4 days after acute cholinergic effect - and the signs are no longer obvious

*weakness of respiratory muscles and accessory muscles - neck and proximal limb

Question 17

T/F: The length of time of OP binding to the Ach-esterase complex has no effect on the ability to be reversed

Answer 17

FALSE

Ageing occurs - conformation change in OP-Ach-esterase complex that results in increased or irreversible binding of the complex

longer time = stronger binding ability

this is non-competitive inhibition

Question 18

What is the most likely cause of death in animals with OP toxicosis?

Answer 18

Respiratory failure due to increased lung mucus production and airway obstruction

the patient can have acute death with no specific lesions

Question 19

When testing plasma ach-esterase activity levels; what % of activity is diagnostic for OP toxicosis?

Answer 19

Less than 25%

Less than 50% activity is considered suspicious

Question 20

What test can be performed to aid in diagnosis of OP tox?

Answer 20

Atropine response test

-admin atropine and wait 15 mins:
If atropine positive - increased HR, moderately dilated pupils etc = LOW likely hood of OP poisoning

If atropine negative - few or none of those signs will be seen = high likely hood of OP poisoning

Question 21

How should OP poisoning be treated?

Answer 21

Decontamination, supportive care, atropine (used to reduce the effects of excessive Ach stimulation since atropine is a parasympatholytic)

other tx includes - cholinesterase reactivators - “oximes”

Question 22

what is the most toxic of the carbamates?

Answer 22

Aldicarb

It is synthesized to mimic the structure of ACh

Question 23

T/F: Carbamates penetrate the CNS

Answer 23

FALSE

they do NOT penetrate CNS - effects are mostly respiratory

Question 24

Do carbamates require hepatic bioactivation?

Answer 24

NO

Question 25

When compared to OPs, Carbamates have a _____ onset, and _____ duration

Answer 25

Faster onset

shorter duration

Question 26

what is the mechanism of action of carbamates?

Answer 26

REVERSIBLE inhibition of ACh-esterase

**competitive inhibition

Question 27

What signs do you expect to see in a patient with carbamate poisoning?

Answer 27

SLUD signs

salvation
lacrimation
urination
dhr

***death usually results from resp. failure and hypoxia due to bronchoconstriction leading to tracheobronchial secretion and pulmonary edema

Question 28

T/F: The atropine test can be used to diagnose carbamate poisoning

Answer 28

TRUE

Question 29

What is the prognosis of patients with carbamate poisoning?

Answer 29

Good - it treatment is started soon after onset of clinical signs

Question 30

In regards to toxicity, which option is false?

1. phosphate OPs require hepatic bioactivation
2. Thiophasphate OPs do not require hepatic bioactivation
3. Carbomates require bioactivation
4. All of the above
5. None of the above

Answer 30

all of the above