Toxicology Flashcards
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.
What is the mortality for cats developing AKI from lily toxicity
50-100% mortality
What it the mortality for dogs developing AKI from grape toxicity
Up to 50% mortality
(18% of survivors never had a return to normal of their creatinine)
What is the mechanism of action / toxicity of cocaine
- Inhibition of reuptake of norepinephrine, serotonin, dopamine
- Stimulation of endogenous catecholamine release
- Neuroendocrine system dysregulation -> altered sleep, appetite, temperature
Mechanism of action / toxicity of amphetamines
- Inhibition of monoamine oxidase
- Increased catecholamine release
- Direct serotonin and dopamine receptor agonism
What is the toxic dose of xylitol? What is the timing of onset of toxicity?
- Hypoglycemia: 0.1 g/kg, happens very quickly for 12-48h
- Hepatotoxicity: > 0.5 g/kg, happens 9-72h after ingestion
What is the toxic dose of methylxanthines (caffeine, theobromine) in dogs
- 20 mg/kg ->GI, PUPD
- 40-50 mg/kg ->arrhythmias
- > 60 mg/kg -> CNS (seizures)
What is the mechanism of toxicity of iron? Clinical signs? Treatment?
Very reactive ion causing oxidative damage (mostly to GI, liver, cardiovascular system) ->vomiting, diarrhea, GI ulceration (and possible secondary stricture), vasodilation, hypotension
Treatment with chelation by deferoxamine until iron < TIBC
What are the primary systems affected in lead toxicosis? What is the treatment?
Mostly GI and nervous systems (vomiting, diarrhea, seizures, blindness, confusion, megaesophagus) + anemia due to increased RBC fragility and decreased Hb synthesis
Chelation with CaNa2EDTA or succimer (DMSA)
What treatments can be used for calcium channel blockers toxicosis
- Intralipids (can increase entry of Ca into cells)
- Calcium gluconate or calcium chloride - target iCa 1.5-2 times upper range (might improve contractility)
- Glucagon (has Gs receptors in cardiomyocytes -> cAMP -> increased contractility and chronotropy)
- High-dose insulin with dextrose infusion (improves inotropy and cardiac output, unclear mechanism but possible increase in carbohydrate intake as energy source and improved Ca entry into cells): insulin up to 2 U/kg/h and dextrose up to 30%!
How does xylitol cause hypoglycemia?
Stimulation of insulin release from beta cells + hepatic necrosis and failure
What component of marijuana causes the toxicity?
Delta-9 THC
What medication can be used in case of severe beta-blocker overdose with cardiac depression
Glucagon (has Gs receptors in cardiomyocytes -> increases inotropy and chronotropy independently of beta receptors)
What is the mechanism of action of N-Acetylcysteine for treatment of acetaminophen toxicity?
- NAC is a glutathione precursor –> binds with APAP metabolites making them inactive
- Sulfur donor –> increases sulfate conjugation
- Decreases methemoblobinemia and Heinz body formation
What is a common biochemical finding in cats with lily toxicity?
More markedly elevated serum creatinine compared to a more moderate BUN
