Toxicology Flashcards
(38 cards)
What is the toxic dose for acetaminophen in cats and dogs
Cats: 10 mg/kg (but most commonly 50-100 mg/kg)
Dogs: 100-200 mg/kg
What is the recommended treatment in case of severe cardiovascular collapse due to a local anesthetic overdose
- Positive inotrope if decreased isotropy
- Amiodarone in case of arrhythmias (no lidocaine lol)
- Small doses of epinephrine in case of hypotension or cardiac arrest
- Intravenous lipid emulsion
Name toxins for which the use of intralipid emulsion would be recommended
- Marijuana
- Macrolytic lactones (ivermectin, moxidectin)
- Local anesthetics
- Calcium channel blockers
- Permethrin
- Cyclic antidepressants (amitriptyline)
- Muscle relaxants
- Psychotropic drugs
What chemical properties of toxins allows prediction of potential benefit of intralipid emulsion
Lipophilicity -> quantified by partition coefficient (log P)
If logP > 1, toxin is lipophilic and ILE could be beneficial
Benefit of ILE most likely if logP > 5
What is the mechanism of action of intralipids
- “Lipid sink”: causes an expanded lipid phase in the plasma leading to sequestration of lipid compounds and decreasing their concentration in target tissues
- Increased circulating free fatty acids -> energy substrate for myocardial cells -> improved myocardial function (likely to be useful especially for bupivacaine toxicosis which blocks mitochondrial use of free fatty acids)
- Activation of voltage-gated calcium channel -> increased intracellular calcium (likely to be useful especially for calcium channel blockers)
What is the recommended dose and maximum dose for intralipids
1.5 mL/kg bolus followed by 0.25-0.5 mL/kg/min for 30-60 min
Do not exceed 10 mL/kg/day ; typically do not administer over more than 24h
How should the modality of treatment be decided for extra-corporeal toxin removal
Based on volume of distribution, protein binding, molecular weight, charcoal affinity
Name examples of toxins that can be removed by hemoperfusion
- NSAIDs (but TPE better)
- Caffeine
- Theobromine
- Barbiturates
- Vincristine
Mechanism of action of anticoagulant rodenticides
Inhibition of vitamin K epoxide reductase in liver -> no activation of vitamin K -> no gamma-carboxylation of factors II, VII, IX, X and proteins C and S
Indicate if the following anticoagulant rodenticides are first or second generation:
- brodifacoum
- warfarin
- diphacinone
- bromadiolone
What is the difference?
- First generation: warfarin, diphacinone
- Second generation: brodifacoum, bromadiolone
Second generation rodenticides have a longer half-life
Mechanism of action of bromethalin and delay of onset of clinical signs
- Neurotoxic: uncouples oxidative phosphorylation -> decreased ATP production
- Delay of 2h to 5 days depending on ingested dose (poor prognosis once clinical signs have developed)
Name the 3 non-anticoagulant rodenticides and their effects
- Bromethalin -> neurotoxic
- Cholecalciferol (vitamin D3) -> hypercalcemia, hyperphosphatemia
- Zinc and aluminum phosphides -> direct toxicity to heart, kidneys, adrenal glands, and corrosive agent
What can be used to decrease GI absorption of cholecalciferol
- Activated charcoal q6h for 24h (entero-hepatic recirculation)
- Cholestyramine resin for 4 days
What is the mechanism of action of phosphide rodenticides? What precaution should be taken with decontamination?
- Direct corrosive effect
- Inhibition of cytochrome C oxidase, disruption of mitochondrial membrane -> free radicals -> lipid peroxidation
The active compound (phosphine) is a gas ->gas exposure can happen after induction of emesis, do it outside
What are the ethylene glycol metabolites and their toxic effects
- Glycoaldehyde -> CNS signs
- Glycolid acid -> metabolic acidosis, high anion gap
- Oxalic acid -> binds calcium -> calcium oxalate crystals -> AKI, hypocalcemia
What are the 3 phases of ethylene glycol toxicosis (with timing for cats and dogs)
- Within a few hours: CNS and GI signs ->vomiting, ataxia, depression, muscle fasciculations, possible seizures
+ PUPD from osmotic diuresis
- Neuro signs can resolve in dogs after 12h
- 12-24h after ingestion: Cardiopulmonary signs -> tachypnea, arrhythmias (from hypocalcemia and acidosis)
- 12-24h after ingestion in cats, 24-72h in dogs: AKI
What is the timing for increased osmolal gap in dogs with ethylene glycol toxicity
Increased as soon as 1h post-ingestion, peaks at 6h, stays elevated for ~48h
What is the goal of ethylene glycol antidote therapy
Competitive inhibition of alcohol dehydrogenase by administration of ethanol or fomepizole (4-MP)
What is the dose for fomepizole / ethanol as an antidote for ethylene glycol toxicity
- Fomepizole:
Dogs: 20 mg/kg IV then 15 mg/kg IV at 12 and 24h then 5 mg/kg IV at 36h
Cats: 125 mg/kg IV initially, then 31.25 mg/kg IV at 12, 24, and 36 hours - Ethanol:
Dogs: 1.3 mL/kg IV bolus of 30% ethanol followed by CRI 0.42mL/kg/h for 48 hours OR 5.5mL/kg of 20% ethanol IV q4 for 5 treatments then q6 for 4 treatments
Cats: 5mL/kg of 20% ethanol IV q6 for 5 treatments and then q8 for 4 treatments
What is the metabolism of acetaminophen
- Glucuronidation and sulphuric acid conjugation (dogs)
- Sulfation (cats)
- If saturated, oxidation by cytochrome P450 enzymes (CYP2E1 and CYP1A2) to toxic metabolite NAPQI (N-acetyl-P-benzoquinone imine) -> converted to non-toxic metabolites by glutathione
Mechanism of toxicity of acetaminophen
- NAPQI binds to hepatic cell membranes -> hepatic necrosis
- Glutathione depletion -> MetHb in dogs and cats + Heinz body anemia in cats
- Hypoxia and increased capillary permeability -> facial edema
- NAPQI damages renal proteins -> cell death
What are the toxic doses for aspirin, ibuprofen and naproxen in dogs and cats
- Aspirin: GI ulcerations at 25-100 mg/kg. Lethal at > 450 mg/kg in dogs and > 100 mg/kg in cats
- Ibuprofen:
Dogs: GI signs at 100-125 mg/kg, AKI at 175-300 mg/kg, CNS at > 400 mg/kg, lethal at > 600 mg/kg
Cats: twice as sensitive - Naproxen: GI signs at > 5 mg/kg, AKI at 10-25 mg/kg, CNS at > 50 mg/kg (not established for cats)
- Very long half life (74h)
What is the toxic agent in grapes / raisins
Tartaric acid
Name 4 examples of nephrotoxic lilies
Easter lily, Asiatic lily, Trumpet lily, White lily, Yellow lily, Tiger lily, Leopard lily, Panther lily, Japanese show lily, etc.
