Op/Carbamates/pyrethrins Flashcards
What are chlorinated hydrocarbons?
- Highly lipid soluble
- Persistent in environment
- Bioaccumulate
- Largely removed from market
What are the toxicokinetics of Chlorinated hydrocarbons
- All animals susceptible
- Lipid soluble - rapid absorption
- Distribution to liver, kidney, brain, fat
- Metabolism by mixed function oxidases to more toxic epoxides (for cyclodiene)
- Excreted in bile and milk fat
- Released to blood during weight loss
- can cause bimodal progression of signs
- Toxicosis after some other issue
- Excretion half-life may have two compartments
What is the MOA of chlorinated hydrocarbons?
- Lowers action potential thresholds
- especially in CNS
- Affects GABA receptors, similar to strychnine
What is the MOA of Diphenyl aliphatics (DDT)?
- Interfere with Na+ flow in nerves
- Lowers threshold for action potential
What is the MOA of Cyclodienes?
- Inhibit prostynaptic binding of GABA
- lowers threshold
What are the toxicity levels of chlorinated hydrocarbons?
- Cats most sensitive - LD50 3-6 mg/kg
- Dog LD50 50-65 mg/kg
- Cattle min tox dose 10-25 mg/kg
What are the toxic levels for Lindane?
- LD50:
- Cats 25 mg/kg
- Dog 40 mg/kg
What is the clinical picture associated with chlorinated hydrocarbon toxicosis?
- Acute onset 12-24 hours
- Behaior changes
- hypersensitive, beligerent, walking backwards
- Muscle tremors
- especially head, face, neck
- Tono-clonic convulsions
- intermittent CNS depression
- Almost appear normal between episodes
- Death due to respiratory failure
How can chlorinated hydrocarbon toxicosis be diagnosed?
- Clin path not helpful
- Acute toxicosis
- Measures residues in GI content, brain, liver
- Body fat good sample as well
- Milk, eggs
- Long half-life
- Measures residues in GI content, brain, liver
- No specific lesions or no lesions at all
How is chlorinated hydrocarbon toxicosis treated?
- Supportive care:
- Control seizures -diazepam, phenobarb
- Activated charcoal and cathartics
- Wash with soup and water if dermal exposure
- Prognosis variable
What chlorinated hydrocarbon is responsible for thin eggshells?
DDT (Deet)
What are Pyrethrins/Pyrethroids?
- Pyrethrins:
- Extracts of Chrysanthemum
- Not very stable
- Pyrethroids
- Synthetic
- Stable
- Permethrin, cypermethrin, fenvalerate
What are the classes of Pyrethroids?
- Type I (no a cyano)
- allethrin
- permethrin
- phenothrin
- resmethrin
- sumithrin
- telfluthrin
- tetramethrin
- Type II (has a cyano)
- Cyfluthrin
- Cyhalothrin
- Cypermethrin
- Deltamethrin
- Fenvalerate
- Flumethrin
- Fluvalinate
What are the classes of Pyrethroids?
- Type I (no a cyano)
- allethrin
- permethrin
- phenothrin
- resmethrin
- sumithrin
- telfluthrin
- tetramethrin
- Type II (has a cyano)
- Cyfluthrin
- Cyhalothrin
- Cypermethrin
- Deltamethrin
- Fenvalerate
- Flumethrin
- Fluvalinate
What sit the MOA of Type I pyrethroids?
- Slow the opening and closing of neural sodium and K+ and CL= channels
- Lowers the threshold for firing of nerve and extends the action potential
- CNS stimulation, muscle tremors, excitement
What sit the MOA of Type II pyrethroids?
- Membrane depolarization predominates
- Affects GABA (inhibitory) channels
- Tendency to weakness, paralysis
What is the clinical picture associated with pyrethroid toxicosis?
- Onset often <1hr
- Hyper excitable, tremors, seizures, ataxia, vomiting
- Some products (type II) include more salivation, weakness, abnormal posture
- Clinical poisoning usually goes to recovery (rarely death ) in 24-72 hrs
- Topical allergic pruritus, hyperemia, urticaria, dermatitis not common
What is the affect of Permethrin in Cats?
- Toxicosis has occurred from contact with spot on treated dogs
- Onset 2 min - 3 hrs
- Hypersalivation, vomiting seizures, paw shaking, ear twitching, flicking of tail, twitching of dorsal skin
- Agitation, seizures can occur 12-24 hrs post exposure
- Seizures may be difficult to control
How is pyrethroid toxicosis diagnosed?
- History of exposure
- General lab tests- Increased PMNs, glucose
- Chemical analysis- brain, skin
- Analysis shows presence not peak concentration
What are differential diagnoses for pyrethroid toxicosis?
- OPs
- Clorinated hydrocarbons
- metaldehyde
- nicotine
- strychnine
What is the treatment for pyrethroid toxicosis?
- Discontinue exposure, control tremors, general supportive care
- Bathe with detergent (Dawn)
- Methocarbamol (Robaxin) for tremors
- Alternatively use valium or pentobarbital
- Supportive care: fluids, thermoregulation
- Check for hypoglycemia and treat as needed
- Most recover in 24-72 hours
What is the chemical structure of Organophosphates?
- Aliphatic, cyclic, or heterocyclic esters of phosphoric acid
- have P=O bond adjacent to the ester
- more toxic
- Organothiophosphates have a P=S group
- More stable in environment
- Phase I mixed function oxidases - Lethal synthesis
What is the ADME of OPs?
- Absorption rapid and complete
- Distributed in plasma⇢ liver⇢ CNS
- Metabolized by MFO system (oxidation)
- deactivated by hydrolysis
- Excretion of metabolites in urine and feces
What is the toxic level of OPs?
- LD50s less than 10 mg/kg
- Cats> dogs
- Brahman cattle > English
- Bulls > cows
- Poultry very susceptible to divhlorvos
Wat is the MOA of OPs?
- Inhibit acetylcholinesterase at cholinergic synapses
- allows for continuous stimulation by accumulated acetylcholine
What are the signs of OP toxicosis?
- Signs reflect stimulation of parasympathetic nervous system and neuromuscular junctions
- Muscarinic - SLUD syndrome
- Nicotinic - tremors, ataxia, paralysis
What is the clinical picture of OP toxicosis?
- Acute onset - minutes to hours
- Parasympathetic stimulation - muscarinic
- SLUD, Emesis, bronchoconstriction, miosis, bradycardia
- neuromuscular - nicotinic
- Muscle tremors, stiffness, paralysis
- CNS
- apprehension, nervousness, seizures
- death from respiratory failure
How is OP toxicosis diagnosed?
- Clinical signs
- History of exposure
- Cholinesterase activity
- Blood, Brain, retina acceptable
- Carbamate exposure regeneration to normal
- Chemical analysis
- detection of parent compound
What are the differential diagnoses for OP toxicosis?
- Chlorinated pesticides
- Strychnine
- Pyrethroids
- Zinc phosphide
- Nicotine
What is the treatment for OP toxicosis?
- Atropine sulfate ¼ IV rest SQ
- SA - 0.2 mg/kg
- LA - 0.5 mg/kg
- Atropine loses efficacy after 2-3 doses
- Do NOT OD
- USE with extreme caution in horses (GI stasis)
- Glycopyrrolate - alternate
- doesn’t cross BBB
- Oral activated charcoal
- Reactivator oximes like 2-PAM
- must give before aging
- AChE irreversible binding
- NOT for carbamates - spontaneously hydrolyze
- Dermal - wash with soap and water
