Organophosphates Flashcards
What are the uses for Organophosphates?
Animal and plant insecticides insecticide synergists antihelmintics antiglaucoma Soil nematocides fungicides herbicides rodenticides insect repellants
What are the sources for Organophosphates?
Contaminated feed or water
Empty pesticide containers used for feeding and watering animals
Dusting or spraying animals or animal premises
Overdosing
What is the mechanism of Action of Organophosphates?
Irreversibly inactivates acetylcholinesterase
What is the most common organophosphate?
Malathion
How long do Organophosphates persist in the environment?
2-4 weeks
What is “Storage Activation”?
If sealed and stored 1-2 years it is more toxic
What is the solubility of Organophosphates?
Lipid soluble
What is the difference between Technical grade and pure compounds?
Technical grades are more toxic
What are the two types of Organophosphates?
Phosphates
Thiophosphates
Phosphates
biologically active
direct effect on Acetylcholinesterase activity
Thiphosphates
require hepatic activation
Desulfurated by liver enzymes
What are thiophosphates transformed into?
-oxon metabolites
Are Thiophosphates biologically active?
NO
What is the solubility of Thiophosphates?
Lipid Soluble
What is the major route of elimination of Thiophosphates?
paraoxonase
What are the toxicokinetics of Organophosphates?
Lipophilic
Metabolized in the Liver
Lethal Synthesis of Thiophosphates in the Liver
How are Organophosphates absorbed?
Dermally
Orally
Inhaled
What can continued exposure of Organophosphates lead to?
Adaption to decreased acetylcholinesterase
Receptor down-regulation or decrease in acetylcholine receptor
What are the 3 steps of Irreversible inhibition of cholinesterase
- Muscarinic receptor over stimulation
- Nicotinic receptor over stimulation
- Nicotinic blockade
High exposure to Organophosphates can lead to what?
respiratory failure
paralysis
death
What are the Muscarinic clinical signs of Organophosphates?
Diarrhea Urination Miosis Bronchospasm Emesis Lacrimation Salivation
“DUMBELS”
What are the Nicotinic clinical signs of Organophosphates?
Fasciculations of muscles
Sweating
Hypertension
tachycardia
What are the CNS clinical signs of Organophosphates?
Increased sensory and behavioral disturbances
incoordination
depressed motor function
respiratory depression
What are usually the clinical signs that lead to death?
Respiratory failure from increased pulmonary secretions
What are the delayed effects of Organophosphates?
10-14 days after exposure
muscle weakness
ataxia
rear limb paralysis
Organophosphate-induced intermediate syndrome
2-4 days after acute cholinergic effect
NO muscarinic or muscle fasciculations
Weakness of respiratory muscles and accessory muscles including neck muscles and of proximal limb muscles
What kind of inhibition does Organophosphates cause?
Non-competitive inhibitiom
What tissues do you detect Organophosphates in?
Stomach or rumen contents
analysis of the hair and skin
What is a laboratory test for diagnosis of Organophosphates toxicosis?
Plasma Acetylcholinesterase activity level
What is a clinical test for diagnosis of Organophosphates toxicosis?
Atropine Response Test
What are the signs seen in an animal with the atropine test that is negative for Organophosphate toxicosis?
Dry skin and mucous membranes
increased heart rate
dilated pupils
decreased bowel sounds
How do you treat Organophosphates toxicosis?
Decontaminate: Emesis, Activated Charcoal, or Bathing the animal
Supportive care
Atropine
Cholinesterase reactivators - “oximes”
What drugs do you avoid with Organophosphate toxicosis?
phenothiazines
aminoglycosides
muscle relaxants
opoids
How do you treat Organophosphate induced delayed polyneuropathy?
Symptomatic therapy ONLY
How do you treat Organophosphate induced intermediate syndrome?
Supportive care
2-PAM chloride - “oximes”
What is the mechanism of Action of 2-PAM chloride “oximes”?
binds to Organophosphate inactivated acetylcholinesterase to reverse Organophosphate binding
What is the prognosis of Organophosphates?
Good if presented alive with no clinical signs
Treatable, if presented with mild to moderate clinical signs
If presented with multiple clinical signs, level of various treatments may depend on finances
