Organophosphates & Carbamates Flashcards
Where are organophosphates naturally occurring?
Associated with DNA, RNA, and many cofactors that are essential for life
Organophosphates will irreversibly inactivate __________
acetylcholinesterase
*meaning the animal will have persistent Ach activity
Organophosphates are subject to storage activation, what does that mean?
If sealed and stored for 1-2 years, it can become more toxic
*impurities will cause these compounds to be more toxic
Thiophosphate OPs are more or less lipid soluble than phosphate OPs?
MORE lipid soluble
What are the most common means of OP toxicosis in animals?
**since these compounds are lipophilic they are readily absorbed through the skin and mm, GIT, and inhalation
*dermal, oral, inhaled
Where do OPs distribute in the body?
usually well distributed throughout the body in most cells, including the CNS
Where are OPs metabolized?
In the liver - excretion and bioactivation take place
*LETHAL SYNTHESIS - CYP450 liver enzymes metabolize or bioactivate thiophosphate OPs
What OPs will undergo lethal synthesis in the liver?
Thiophosphate OPs
What changes will occur in the body of an animal that is chronically exposed to OPs?
- 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)
There are two types of Organophosphates:
- _________ : these are biologically active
- __________: these require liver metabolism to become active (lethal synthesis)
- phosphates
2. Thiophosphates
What is the major route of elimination of thiophosphates?
paraoxonase - a serum bound enzyme
Thiophosphates are rapidly absorbed by what tissue?
Adipose tissue (lipid soluble)
*a slow release from fat may lead to delayed or prolonged cholinesterase inhibition
What are the 3 consequences of OPs irreversible inhibition of cholinesterases?
- Muscarinic receptor over stimulation
- Nicotinic receptor over stimulation (CNS stimulation - muscle fasiculations)
- Nicotinc blockade (CNS depression - paralysis)
Occurs in that order
What signs would you expect to see in a patient with over stimulation of muscarinic receptors?
= 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)
what animals are most sensitive to organophosphate-induced delayed polyneuropathy?
Chickens
*this occurs 12-14 days post exposure
muscle weakness, ataxia, rear limb paralysis
What is the time frame of development of OP-induced intermediate syndrome?
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
T/F: The length of time of OP binding to the Ach-esterase complex has no effect on the ability to be reversed
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
What is the most likely cause of death in animals with OP toxicosis?
Respiratory failure due to increased lung mucus production and airway obstruction
the patient can have acute death with no specific lesions
When testing plasma ach-esterase activity levels; what % of activity is diagnostic for OP toxicosis?
Less than 25%
Less than 50% activity is considered suspicious
What test can be performed to aid in diagnosis of OP tox?
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
How should OP poisoning be treated?
Decontamination, supportive care, atropine (used to reduce the effects of excessive Ach stimulation since atropine is a parasympatholytic)
other tx includes - cholinesterase reactivators - “oximes”
what is the most toxic of the carbamates?
Aldicarb
It is synthesized to mimic the structure of ACh
T/F: Carbamates penetrate the CNS
FALSE
they do NOT penetrate CNS - effects are mostly respiratory
Do carbamates require hepatic bioactivation?
NO
When compared to OPs, Carbamates have a _____ onset, and _____ duration
Faster onset
shorter duration
what is the mechanism of action of carbamates?
REVERSIBLE inhibition of ACh-esterase
**competitive inhibition
What signs do you expect to see in a patient with carbamate poisoning?
SLUD signs
salvation
lacrimation
urination
dhr
***death usually results from resp. failure and hypoxia due to bronchoconstriction leading to tracheobronchial secretion and pulmonary edema
T/F: The atropine test can be used to diagnose carbamate poisoning
TRUE
What is the prognosis of patients with carbamate poisoning?
Good - it treatment is started soon after onset of clinical signs
In regards to toxicity, which option is false?
- phosphate OPs require hepatic bioactivation
- Thiophasphate OPs do not require hepatic bioactivation
- Carbomates require bioactivation
- All of the above
- None of the above
all of the above
