4.5 Lab Flashcards
most common types of rodenticide?
Anticoagulants are the most common type of rodenticide
First generation: Warfarin and indanedione (less common)
Second generation: bromadiolone, brodifacoum
toxicokinetics of anticoagnulant rodenticides? average duration?
Well absorbed orally
Highly bound to plasma proteins
Metabolized in liver and excreted in urine
Average duration of toxicosis:
14 days, warfarin
21 days, bromadiolone
30 days, brodifacoum
mechanism of toxicity of anticoagulant rodenticides
Blocks vitamin K-dependent clotting factor (prothrombin) synthesis in the liver by inhibiting vitamin K epoxide reductase
Stops vitamin K recycling needed for factors II, VII, IX and X synthesis –
Clinical signs appear 3-7 days after ingestion (i.e. after activated clotting factors are depleted by natural degradation)
- Anticoagulants antagonize vitamin K, which interferes with the normal synthesis of coagulation proteins factors I, II, VII, IX, and X in the liver
- thus, adequate amounts are not available to convert prothrombin into thrombin.
Typical clinical presentation of anticoagulant toxicity
- Clinical signs generally reflect some manifestation of hemorrhage, including anemia, hematomas, melena, hemothorax, hyphema, epistaxis, hemoptysis, and hematuria, any of which may lead to weakness, ataxia, colic, polypnea, etc.
- Petechiae rarely develop until after repeated small bleeds have consumed too many platelets.
Sudden death with no obvious clinical signs is also possible! That’s a scenario where a postmortem examination can bring the owner a lot of closure!
how can we diagnose anticoagulant toxicity?
History, clinical signs, physical exam
Lab evaluation: Prothrombin time (PT), useful as occurs early, also activated partial thromboplastin time (aPTT)
Chemical detection in fluids, vomitus, baits
PM Lesions: blood-filled cavities and GI tract
what are the best samples to send for an anticogulant screen?
Turn around time - 7-10 d > in a live animal, treat presumptively!
Liver and serum are the best samples
how can we treat animals exposed to anticoagulant rodenticides?
Recent exposure: Decontamination; induce vomiting, AC or lavage
Monitor PT, aPTT; if normal no further tx
Vit K therapy: if high PT or toxic dose ingested, given orally with food
Dose and length of treatment of vitamin K based on dose and type of anticoagulant (see duration of action – up to 30 days)
Check PT 48 h after last vitamin K tx
If symptomatic: give whole blood, high dose injectable vitamin K, cage rest, serial coagulation profiles, restrict exercise
prognosis for animals that ingest anticoagulant rodenticide? how can we prevent ingestion?
Prognosis:
Animals with mild clinical signs recover in 1-2 weeks
If severe clinical signs including coma, paralysis are present – poor prognosis
Prevention: restrict access to bait; educate clients
what are the toxicokinetics of cholecalciferol rodenticides? where are they stored in the body?
Toxicokinetics:
Well absorbed orally
Clinical signs in 12-36 h
Fat soluble; stored in adipose tissue
Bound to plasma proteins
what is cholecalciferol? what does it do?
vitamin d3, helps body absorb calcium
mechanism of toxicity of cholecalciferol. what are early clinical effects? what can lead to end-stage signs?
Vit D and metabolites increases Ca and P absorption from GIT
Osteoclastic resorption and Ca mobilization from bone > >SO MUCH CALCIUM!!!
Early clinical effects (48h) due to effect of increased plasma Ca on cells:
Altered cell membrane permeability
Altered Ca pump activity
Decreased cellular energy production
Cellular necrosis
Mineralization in kidneys, GI tract, cardiac and skeletal muscle, blood vessels and ligaments leading to loss of function & end-stage signs
clinical signs of cholecalciferol toxicity
Seen at 0.5 mg/kg = 1⁄2 tablespoon of pellets for 12 kg dog
Vomiting & diarrhea
Anorexia and depression
Fulminant acute renal failure (in 24-48 h)
Survivors have renal, cardiac and musculoskeletal loss of function
how can we diagnose cholecalciferol toxicity? PM lesions?
Increased plasma Ca and P (Ca X P may = 130)
Increased BUN and creatinine, urine SG = isothenuria
PM lesions: diffuse soft tissue mineralization
> Oral and gastric mineralization, ulceration and hemorrhage
> Renal tubular mineralization; casts
> Cardiac necrosis; mineralized myocytes
how can we treat cholecalciferol toxicity?
Decontamination: induce vomiting, activated charcoal, gastric lavage; repeat if necessary
Monitor serum Ca, P, BUN, creatinine for 4 days; if normal no further tx
If symptomatic, diuresis with 0.9% saline, furosemide ➝ increases renal Ca excretion Oral prednisone decreases serum Ca
If severe, use bisphosphonate to decrease bone resorption of Ca
cholecalciferol toxicity prognosis? prevention?
Prognosis:
Good if treated promptly before tissue mineralization Prognosis varies with length and severity of increases
Ca:P
Prevention: restrict access to bait; educate clients
bromethalin rodenticides toxikokinetics? stored where?
Well absorbed orally
Metabolized in liver to toxic N-demethylated metabolite
Fat soluble; stored in adipose tissue and brain
Excreted slowly in bile (t1/2= 5 d)
bromethalin rodenticides mechanism of toxicity
- Uncouples oxidative phosphorylation ➝ decr ion channel pump activity ➝ decr osmotic gradients ➝ incr pressure on axon, cerebral edema, decr nerve impulse conduction, paralysis
bromethalin rodenticides clinical signs of toxicity
– Onset of clinical signs (hours to days) is dose-dependent
– High dose: tremors, hyperthermia, hyperexcitability, seizures
– Low dose: slower onset (days), hind limb ataxia, paresis, paralysis, CNS depression ➝ coma
bromethalin rodenticide toxicity diagnosis
- History of exposure
- Increased CSF pressure (CSF otherwise normal)
- Cerebral edema, spongy degeneration of CNS white matter
- Bromethalin residues in fat and brain
bromethalin rodenticide toxicity treatment
Decontamination: induce vomiting, gastric lavage, activated charcoal; repeat if necessary
Use of mannitol and corticosteroids has been suggested to treat clinical signs, because they may help manage cerebral edema due to other causes.
> However, this has not been shown to be very helpful, likely because of the presence of intra-myelin edema.
Phenobarbital or diazepam for seizures
bromethalin rodenticide toxicity prognosis
Good if treated promptly
Mild clinical signs, prolonged recovery (1-2 wks) Severe signs, poor prognosis
zinc phosphide rodenticide toxicokinetics
Zinc phosphide forms phosphine gas in acidic gastric
conditions
Distinctive rotten fish/garlicky odour
Inhaled, absorbed through skin, ingested
zinc phosphide rodenticide mechanisms of toxicity
- Phosphine gas blocks cytochrome oxidase
- Inhibition of oxidative phosphorylation ➝ decreased energy production in mitochondria ➝ cell death
zinc phosphide rodenticide clinical signs
– Onset of clinical signs is dose-dependent
– Large dose: death in 3-5 h
– No specific signs
– Initially: diarrhea, abdominal pain, vomiting, anorexia and depression
– Then: rapid, wheezy respirations, vomiting, bloat in large animals
– Terminally: ataxia, weakness, recumbency and struggling, coma and death
zinc phosphide rodenticide diagnosis - what organs are most likely to be damaged? where do we look for signs? what should we do with tissue samples?
- No specific lesions
- Organs with high O2 demand most sensitive (brain, kidneys, liver, heart)
- Renal tubular degeneration & necrosis, hepatocyte degeneration
- Detection of zinc phosphide in stomach
- Submit frozen samples to prevent loss of phosphine gas
IMPORTANT NOTE - vets at risk of inhaling phosphine gas! Protect yourself at PM! Ventilate area!
zinc phosphide rodenticide treatment
Early decontamination: induce vomiting, use antacid to increase gastric pH, lavage with 5% NaOH,
activated charcoal; MgSO4 cathartic
No specific antidote
Correct acidosis, O2 for respiratory problems, corticosteroids for shock, B vitamins, low protein diets for liver failure
zinc phosphide rodenticide prognosis
Guarded-to-poor if showing clinical signs
Better if recent ingestion (within last 1-2 hours)
strychnine toxicokinetics
Rapid absorption in GI tract
Wide distribution so only small amounts (<4 ppm) stay in blood
Metabolized by hepatic enzymes, excreted in urine
strychnine mechanisms of toxicity
- Decreased inhibitory action of glycine on cells of anterior horn of spinal cord;
> Decreased neurotransmitter release from Renshaw cells
=> Excessive excitatory activity, severe muscle spasms, tetanic convulsions, and exaggerated reflex arcs
strychnine clinical signs?
– Highly toxic; dogs most frequently poisoned
– Rapid onset of CS; within 10-120 min – no vomiting seen
– Severity is dose-dependent (e.g. mild ataxia ➝ convulsions)
– Anxiety, respiratory rate, salivation, then ataxia, muscle spasms, stiffness
– Terminally: convulsions with opisthotonus, hyperthermia
– Impaired respiration ➝ death
posture expected due to strychnine poisoning
Opisthotonos: hyperextension of the neck, trunk, limbs and tail
strychnine toxicity diagnosis
- No specific blood and serum chemistry findings
- No specific gross or histologic lesions
- Necrosis of cerebral cortex and brainstem
- Presence of strychnine in tissues (stomach contents are best)
strychnine treatment
Reduce GI absorption, symptomatic and supportive care
Induce vomiting, activated charcoal
Pentobarbital, diazepam to control convulsions
Methocarbamol for muscle relaxation
IV fluids (LR, saline); keep in dark quiet areas
