insecticides, herbicides, millusicides Flashcards
O R G A N O C H L O R I N E I N S E C T I C I D E S – M E C H A N I S M + T O X I C I T Y
- Toxicity: oral LD50 between 15-100 mg/kg for most species
- Mechanism of toxicity: interference with action potentials and neurotransmitters in
the CNS - DDT: interacts with Na+ and K+ influx/efflux
- GABA inhibition
- Enhanced acetylcholine release
- CNS excitation**
organochlorine insecticides toxicokinetics
- High lipophilicity:
- Partition to fatty tissues: adipose, brain
- Excreted in milk
- Very long elimination half-life: months
- Enterohepatic recirculation
organochlorine insecticides clinical features
- Onset: within hours of exposure
- Behaviour: anxiety, agitation/aggression, jumping over invisible objects
- GI: vomiting, salivation
- CNS excitation: tremors, intermittent tonic-clonic seizures, opisthotonus, paddling, jaw clamping,
circling, stiff gait - Progression to coma and death
- No specific PM lesions
organochlorine insecticides management and diagnosis
- No specific antidote
- Decontamination if not contraindicated
- Dermal exposure: wash
- Symptomatic and supportive care
- Anticonvulsants
- Methocarbamol
- Fluids, oxygen, mechanical ventilation
- Consider ILE, cholestyramine
- Diagnosis: some VDLs have pesticide screens (GC/MS) – fat, liver, brain, gastric contents
organophophate and carbamate toxicity
- Toxicity: varies between compounds and species
- Range: 0.2 mg/kg to 1 g/kg
- More acutely toxic than OC insecticides
- Mechanism of action: inhibition of acetylcholinesterase
- CNS, neuromuscular junction, parasympathetic nervous system
- Acetylcholine not broken down → overstimulation of:
- Nicotinic acetylcholine receptors (nAChR)
- Muscarinic acetylcholine receptors (mAChR)
organophosphate vs carbamates mech
Organophosphates
* Irreversibly binds to AChE enzyme
* Enzyme aging – irreversible
inactivation of AChE
carbamates
* Reversible inhibition
* No enzyme aging
* Shorter half-life of inhibition
* Shorter duration of clinical signs
O P + C A R B A M A T E S – C L I N I C A L F E A T U R E S
. Acute toxicosis
* Routes of exposure: ingestion, inhalation, dermal
* Onset: as early as 15 minutes post-exposure
* Three major categories of symptom
symptoms of mAChr overstimulation: SLUDGE
- Symptoms related to nAChR overstimulation
* Muscle fasciculations
* Tremors
* Weakness
* Ataxia
* Muscle stiffness
* Paralysis - Symptoms related to CNS overstimulation
* Anxiety, restlessness
* Depression or hyperactivity
* Tonic-clonic seizures
* Respiratory depression
* Coma
* Death due to:
* Bronchoconstriction/bronchorrhea
* Respiratory failure and hypoxi
symptoms of mAChr overstimulation: SLUDGE in OP + carbamates toxicity
- Symptoms related to mAChR overstimulation
* Salivation
* Lacrimation
* Urination
* Diarrhea
* GI cramping
* Emesis
op + carbanates PM features
No specific PM lesions
* Congestion, edema, hemorrhage
* May observe insecticide granules in
stomach/rumen contents if oral exposure
* Check gastric contents for anything that
resembles bait
op + carbamates 2 intermediate syndrome
- Reported in dogs and cats
- Onset: 24-96 hours after acute cholinergic crisis
- Predominance of nicotinic signs
- Acute muscular weakness: abnormal posture, cervical ventroflexion, respiratory muscle weakness and depression
- Clinical pathology: ↓ AChE activity
op + carbamates 3. OP-induced delayed polyneuropathy (OPIDPN
- Due to degeneration of long motor nerves via inhibition of neuropathy target esterase (NTE)
- Axonopathy, myelinopathy
- 1-4 weeks after exposure to an OP
- Ataxia, pelvic limb weakness
- Clinical pathology: normal blood AChE
op + carbamates management known exposure
- Acute toxicosis
- Antidote: atropine**
- Control of bradycardia and bronchial secretions
- Known OP/carbamate exposure**
- Initial dose: 0.1-0.5 mg/kg depending on severity of muscarinic signs
- Quarter dose given IV + rest IM
- OP: oximes (2-PAM) prior to enzyme aging
- Classic cholinergic toxidrome with unknown exposure
- Same atropine for above
- Consider whether to give 2-PAM
op + carbamates management suggestive exposure
- Acute toxicosis continued
- Suggestive cholinergic toxidrome but no history of exposure
- Test dose of atropine (0.02 mg/kg IV)
- If pupil dilation, increased HR, and salivation stops within 10-15 minutes: not
OP/carbamate - None of the above observed: likely OP/carbamate → give additional atropine
- Supportive care
- Oxygen, mechanical ventilation
- Fluids
- Seizure control
- Anti-emetics
op + carbamates management of intermediate syndrome
- Intermediate syndrome
- No atropine indicated
- 2-PAM (pralidoxime)
- Supportive care
- Slow recovery
- OPIDPN
- No atropine indicated – why not?
- Supportive care
op + carbamates diagnosis
- Acute toxicosis + intermediate syndrome
- History of OP/carbamate use or possible access, SLUDGE signs (acute)
- Clinically for acute toxicosis: response to atropine
- Antemortem: AChE activity of heparinized whole blood**
- <50% of normal: suspicious
- <25% of normal: diagnostic
- Postmortem: brain** AChE activity
- Freeze half of brain
- Analysis of stomach contents, urine, other tissues with pesticide screen (GC/MS
chlorates mech and exposure
-Sodium, calcium, potassium, magnesium
* Concentrates, pellets, or granules
* Exposure scenario: access to concentrates or recently treated forage
* Tastes salty
* Mechansim + toxicity
* Minimum lethal dose: >1 g/kg BW in cattle
* Must consume a large amount to become poisoned
* Target: RBCs, GIT**
* Mechanism: oxidative damage → hemolysis + methemoglobin formation
* Direct mucosal damage
chlorates clinical features
Onset: acute
* GI: anorexia, abdominal pain, diarrhea, salivation
* Weakness, exercise intolerance
* Hemolysis:
- pale, brown or cyanotic MM
-brown discharge from nares, anus, vulva
* Progresses to respiratory difficulty and distress
- Clinical pathology
- Intravascular hemolysis: yellow serum, hyperbilirubinemia, Heinz bodies
- Chocolate brown blood + methemoglobinemia
- Methemoglobinuria
chlorates management and diagnosis
Antidote: methylene blue
* IV, 1 mg/kg BW slow infusion
* IVFT + forced diuresis
* Diagnosis: brown MM, chocolate brown blood
DDX: oxidative damage hemolytic anemia
prognosis: poor
P A R A Q U A T mech and toxicity
- Toxicity: Dog oral LD50: 1 mg/kg to 50 mg/kg
- Target: lungs**
- Accumulation in type I and type II pneumocytes and Clara cells
- Lungs»_space;> plasma
- Mechanism: oxidative damage from free radicals → acute alveolitis
- Lipid peroxidation
- Vesicant: damages mucosal surfaces
paraquat clinical features
. Acute onset – due to caustic action
* GI: vomiting, abdominal pain, diarrhea, GI mucosal ulceration
* Skin contact: blisters
2. Within a few days of exposure
* Development of acute, severe respiratory distress
* Tachypnea, dyspnea, cyanosis, hypoxemia
* Pulmonary edema ** Pneumomediastinum*
* Renal damage, liver damage
3. If the animal survives: development of extensive pulmonary fibrosis
paraquat management and diagnosis
- No antidote
- Supportive care: Mechanical ventilation
- Diagnosis: access to recently treated pasture, access to concentrates
- Tissue quantification
- Antemortem: plasma, urine, vomitus, bait
- Postmortem: lung**, liver, kidney, bait, stomach contents
- DDx: zinc phosphide
- Prognosis: poor to grave
metaldehyde mechanism + toxicity
- Moderately toxic
- Oral LD50 approx. 100-200 mg/kg for most species
- Target organ: CNS**
- Interferes with inhibitory neurotransmitters in the brain → CNS excitation*
- Involvement of GABA, NE, 5HT
metaldehyde clinical features
Onset: within an hour of ingestion
* Restlessness, anxiety
* GI: hypersalivation, vomiting
* CNS: severe tremors, progressing to continuous convulsions
* Hyperesthesia
* Opisthotonus
* Hyperthermia
* Tachypnea, tachycardia
* Death due to respiratory failure
metaldehyde clin path
Clin path
* Metabolic acidosis secondary to seizures and hyperthermia
* Increased CK due to seizures/tremors
* Stomach contents and feces likely to contain metaldehyde granules/pellets
* Blue or green colour
* Apple cider/formaldehyde smell of stomach contents, vomitus
* No specific PM lesions: multiorgan congestion, serosal hemorrhage
