L10. OP, Carbapenems, Pyrethrins Flashcards
Insecticide:
Sources
- Accidental incorporation in feed
- unintended application to crops/forages
- mistaken for feed ingredients
- Mis-use/mis-calculation for use
- sprays, dips, pour-ons, collars
- Unintended species
- Low-level chronic exposure
- cumulative exposure to persistent chemicals
- Accidental Access
- storage areas, garbages
- Malicious Poisoning
Insecticide:
Considerations
- Formulations
- liquids vs granulars vs powders
- Toxicity
- inherent toxicity
- Intended Use
- crop vs. animal products
- Crop products generally more potent and combined with solvents
- Restriced use pesticides
- extreme toxicity, long residual effects, special applications
Chlorinated Hydrocarbons
- Higly lipid soluble
- fat and brain
- Persistent in Environment
- resist degradation
- Bioaccumulate
- repeat exposures
- Largely removed from market
- environmental concerns
Chlorinated Hydrocarbons:
Sources
- Mostly off market
- Old products still exist
- DDT, Chlordane, Dieldrin, Aldrin, Toxaphene
- Accidental access to old storage buildings
- Occasional intentional poisoning
Chlorinated hydrocarbons:
Toxicokinetics
- All aminals susceptible
- Typical routes of exposure
- oral, topical, inhalation
- Lipid soluble
- rapid absorption
- Distribute to liver, kidney, brain, fat
- Metabolism by mixed function oxidases to more toxic epoxides
- Accumulate in brain, fat
- Excreted in bile and milk fat
- Released to blood during weight loss
- can cause bimodal progression of signs
- Toxicosis after some toher issues
- Excretion half life may have two compartmsents
Chlorinated Hydrocarbons:
MOA
Lowers action potential thersholds
Especially in CNS
Affects GABA receptors; similar to strychnine
- Diphenyl aliphatics (DDT)
- interfere with Na+ flow in nerves
- Lowers threshold for action potential
- Cyclodienes
- Inhibit postsynaptic binding of GABA
- lowers thershold
Chlorinated Hyrdrocarbons:
Toxicity
Cast most sensitive - LD50 3-6mg/kg
Dog - LD50 50-65mg/kg
Cattle minimun toxic dose - 1–25mg/kg
Lindane for ectoparasites in dogs has potential for iatrogenic or accidental exposure
Cats - LD50 25mg/kg
Dogs - LD50 40mg/kg
Chlorinated Hydrocarbons:
Clinical Picture
- Acute onset 12-24 hours
- Behavioral Changes
- hypersensitive, belligerent, walking backwards
- Muscle Tremors
- expecially head, face, neck
- Tono-clonic convulsions
- intermittent CNS depression
- Almost appear normal between episodes
- Death due to respiratory failure
- Behavioral Changes
Chlorinated Hydrocarbons:
DIagnosis
Clinpath not helpful
Acute toxicosis: measure residues in GI content, brain, liver
No specific lesions or no lesions at all
Chlorinated Hydrocarbons:
Treatment
- Treat the patient not the poison
- Symptomatic:
- control seizures - diazepam, phenobarb
- Activaed charcoal and cathartics
- Wash with soap and water if dermal exposure
- Pronosis vairable based on exposure
- Consider environmental persistance
Chlorinated Hydrocarbons:
Environmental and Food Safety
All aniamls species are targets
Potential for relay intoxication exist
Eggshell thinning in birds - DDT
Bio magnification
Food safety impact
Residues awarness and restricitons
Reportable disease: report to public helath or FDA
Pyrethrins – Pyrethroids
- Pyrethrins:
- extracts of Chyrsanthemum
- Not very stable in the environment
- Pyrethroids
- synthetic, stable
- Permethrin, cypermethrin, fenvalerate
Pyrethrins - Pyrethroids:
Source
Quick nock down fly spray
premise fly control products
Many dips, spot ons, sprays, shampoos, ear tags, crop sprays
Ready to use generally < 2% active ingredient
Spot on products 40-65% concentration
Pyrethrins - Pyrethroids:
Type 1
Allethrin
Permethrin
Phenothrin
Resmethrin
Sumithrin
Telfuthrin
Tetramethrin
Pyrethrins - Pyrethroids:
Type 2
Cytluthrin
Cyhalothrin
Cypermethrin
Deltamethrin
Fenvalerate
Flumethrin
Fluvalinate
Pyrethrins - Pyrethroids:
Type 1 vs Type 2
Decamethrin - Type 2
Permethrin - Type 1
Pyrethrin - Pyrethroids:
Toxicity
Most quite safe, not very toxic
Toxicity enhanced by synergists
Oral toxicity is very low
Exposure is through the skin or by inhalation
Use of dog products on cats
Permethrin type 1 has high risk in cats
Pyrethrin - Pyrethroids:
MOA
Type 1
Slow the opening and closing of neural sodium and Potassium and Chloride channels
This lowers the threshold for firing of nerve and extends the action potential
CNS stimulation, muscle tremors, excitement
Pyrethrin - Pyrethroids:
MOA
Type 2
Membrane depolarization predominates
Affect GABA channels
Tendency to weakness, paralysis
Pyrethrin - Pyrethroids:
Clinical Picture
Onset often <1hr
Hyper excitable, tremors, seizures, ataxia, vomiting,
Some products (Type2) 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 uncommon
Permethrin in cats
Highest risk for pyrethroid intoxication
- Toxicosis has occured form contact with spon 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 in 12-24 hrs post exposure
- Seizures may be difficult to control
Pyrethrin - Pyrethroids:
Diagnosis
History of exposure
General lab tests - increased PNMs, glucose
Chemiacla analysis - brain, skin
Analysis shows presence not peak concentration
Pyrethrin - Pyrethroids:
Differenctial Diagnosis
Organic Phosphates
Cl-HC
Metaldehyde
Nicotine
Strychnine
Pyrethrin - Pyrethroids:
Treatment
Discontinue exposure, control the tremors, general supportive care
Bathe with detergent
Methocarbamol for tremors
Alternatively use valium or pentobarbital
Supportive care : gluids thermoregulations
Check for hypoglycemia and treat as needed
Most animals recover in 24-72 hrs
Pyrethrin - Pyrethroids:
Environmental and Food Safety Impact
- Fish are extremely sensitve
- shut off tank pump, cover air intake and tank during spraying or fogging in the home
- Toxicity to toher cold blodded species??
- Birds considered relatively resistant
- Exotic species - little safety information
- Food Safely: fencvalerate, cypermethrin, flucythrinate have possible residue concerns
Organophosphate and Carbamate Insecticides:
Background
Part of a massive and diverse family of compounds
Commonly used in agriculture, home, and gardens since 1970s
Highly lethal
Chemical warfare agent
Organophosphate and Carbamate Insecticides:
Sources
External parasite products
Both large and small animals
Agriculture
Home garden insecticide
Organophosphate and Carbamate Insecticides:
Chemical Structure
- OP → aliphatic, cyclic, or heterocyclic esters of phophoric acid
- OPs have P=O bond adjacent to the ester
- Organothiophophates have a P=S group
- more stable in environment
- P=O is more toxic
- Oxidative desulfuration (P=S → P=O)
- increases toxicity
- Phase 1 mixed funciton oxidases
- lethal synthesis
ADME
- Absorption rapid and complete
- oral, dermal, inhalation routes
- Distributed in plasma → liver → CNS
- Metabolized by MFO system
- deactivated by hydrolysis
- Excretion of metabolites in urine and feces
Organophosphate and Carbamate Insecticides:
Toxicity
Some have LD50s less than 10mg/kg
- Susceptible animals
- all
- cats are more susceptible than dogs
- Brahman cattle are more susceptible than English
- Bull or other males are more susceptible than females
- Poultry very susceptible to dichlorvos
Organophosphate and Carbamate Insecticides:
MOA
Inhibit acethycholinesterase at cholinergic synapses
Allows for continuous stimulation by accumulated asetylcholine
Signs reflect stimulaiton of parasympathetic nervous system and neuromuscular juncitons
Muscarinic - SLUD syndrome
Nicotine - Tremors, ataxia, paralysis
Organophosphate and Carbamate Insecticides:
Clinical Picture
- Acute onset - minutes to hours
- Parasympathetic stimulation → muscarinic
- emesis, salivation, lacrimation, urination, defecation, chornoconstriction, miosis, bradycardia
- Neuromuscular → nicotinic
- Muscle tremors, stiffness, paralysis
- CNS
- apprehension, nervousness, seizures
- Death form respiratory failure
Organophosphate and Carbamate Insecticides:
Diagnosis
- Clinical Signs:
- acute onset, rapid death
- History of exposure
- Cholinesterase activity
- blood, brain, retina acceptable
- Carbamage exposure regeneration to normal
- Chemical analysis
- detection of parent compound
- GI content, hair, bait ro any other suspect material
- detection of parent compound
Organophosphate and Carbamate Insecticides:
Toxic Differentials
Chlorinated pesticides
Strychnine
Pyrethroids
Zinc phosphate
Nicotine
Organophosphate and Carbamate Insecticides:
Treatment
- Atropine sulfate
- Atropine loses efficacy after 2-3 doses
- Do not over atropinize
- Can be used in horses but extreme caution
- GI stasis → colic
- Glycopyrrolate - alternative to atropine
- does not cross the blood-brain barrier
- Oral activated charcoal, may be used as the only Tx in ruminants
- Reactivator oximes
- must give before aging
- AChE irreversible binding
- Not for carbamates
- they spontaneously hydrolze
- Dermal
- wash with soap and water
Organophosphate and Carbamate Insecticides:
Chlorphyriphos
Dursban: topical insecticide
Lorsban - crop insecticide
Cats → intermediate syndrome
Very sensitive, protracted course
Not labeled for cats
Signs: delayed 1-5 days
Organophosphate and Carbamate Insecticides:
Environmental and Food Safety Impact
All animal species are targets
cats, fish, birds most sensitive
Secondary intoxications reported
Food safety impact
Do NOT eat
Amitraz
- Formamidine insecticide:
- topical for controlling ticks, keds, lice, and mites
- Mitaban - for topical use on dogs
- Taktic - mites, lice, ticks on livestock
- Preventic - collars for dog tick control
Amitraz:
Mechanism
Acts as an alpha 2 adrenergic agonist
GI stasis, bradycardia, depression, increased blood glucose, sedation
Rapid oral absorption, plasma peak = 5 hrs
Half life = 24 hrs
Amitraz:
Clinical Signs
- Signs are dose related
- onset within 2-4 hours
- At therpeutic doses
- transient sedation of 2-6 hr duration
- Mild GI signs
- anorexia, vomiting, diarrhea may be seen
- Poisoning more likely
- old, debilitated, diabetic
- With higher doses
- CNS depression
- ataxia, mydriasis, hypthermia, hyperglycemia, bradycardia, hyptension, muscular weakness, emesis, uncontrolled vocal spasm, and mictruition have been noted
- CNS depression
- In horses - COLIC from GI stasis - may be fatal
Amitraz:
Diagnosis
History of exposure
Campatible clinical findings
Hyperglycemia may be suggestive
Chemical detection: stomach content, urine, feces, tissues, blood, skin
Detection only confirms exposure
Amitraz:
Treatment
- Therapeutic dose:
- no treatment needed
- In overdose:
- bathing for topical exposure
- Emetics, gastric lavage or activated charcoal for ingestion
- In dogs:
- yohimbine reverses bradycardia, depression, repeat as needed
- Atipamezole: fewer side effects than yohimbine
- Supportive care
Amitraz:
Environmental and Food Safety Impact
Several animal species are targets
Minimal relay toxicosis
Food safety impacts??
