Toxicology Flashcards
(21 cards)
Which toxins are most commonly implicated in tremorgenic mycotoxicosis?
The penicillium toxins penitrem A and roquefortine
which ticks are most commonly associated with tick paralysis?
Dermacentor sp. or Ixodes sp. (dermacentor in USA, Ixodes in Australia)
What species of snake are implicated in elapid snake envenomation in North America?
Eastern (micrurus fulvius) and Texas (Micrurus tener) coral snakes
Which snake antivenins are cross protective against North American Coral Snake venom?
Tiger snake and mexican coral snake
Which human hairloss medication is associated with death in 12.9% of cats exposed?
Minoxidil
What adverse effects have been associated iwht intralipid emulsion therapy for toxicity?
neurological signs (temporarily reduced consciousness and ataxia), bradycardia, hyperthermia, vomiting, diarrhea, respiratory distress, worsening of the general behavior, facial swelling, and thrombophlebitis (frontiers paper)
what do anticoagulant rodenticides antagonise?
vitamin K epoxide reductase
What features of NSAID toxicity make them good candidates for TPE?
low volume of distribution , highly protein bound (meaning not suitable for dialysis) and small molecular weght
describe the pathophysiology of acetaminophen toxicity and discuss treatment options?
in normal situation, metabolised by phase II conjugating enzymes with glutathione (GSH) or cysteine and converted to non-toxic compounds that are really excreted, less than 10% metabolised by cP450 enzymes to highly reactive intermediate metabolite NAPQI. When intracellular mechanisms to detoxify NAQPI are overwhelmed due to excessive production, there is depletion of intrahepatic GSH stores. NAPQI binds to intracellular proteins leading to hepatocellular necrosis and also causes severe oxidative RBC stress which lead to methaemoglobinaemia and Heinz body formation. Dogs more predisposed to hepatotoxicosis than humans due to intrinsically lower GSH levels. Cats more susceptible than dogs due to absent expression of enzyme UGT1A6 which glucoronidates acetaminophen. In dogs >100mg/kg leads to hepatotoxicosis, >200mg/kg methaemoglobinaemia. Cats no safe dose and haematological effects most common.
Decontamination with emesis and AC best <1hr, worthwhile within 3-4hrs. Give NAC asap (beneficial within 48hrs of ingestion) - replenishes GSH to limit excessive NAPQI formation and therefore limits liver damage. Silymarin/SAMe beneficial too. Ascorbic acid can be given to reduce methaemoglobin into haemoglobin.
Which metabolite associated with azole anti-fungal hepatotoxicity? Which azole least hepatotoxic ?
N-deacetyl ketoconazole
Fluconazole least hepatotoxic
which 2 metabolites are associated with amiodarone induced liver injury?
mono-N-desethylamiodarone (MDEA) and di-N-desethylamiodarone (DDEA)
why are dogs more prone than cats to idiosyncratic hepatotoxicity when receiving potentiated sulphonamides?
The N-acetylation detoxification pathway is absent in dogs and therefore sulphonamides oxidised by cytochrome p450 enzymes to reactive nitroso metabolites
what are aflatoxins produced by and which aflatoxin is most hepatotoxic? What is the toxic metabolite ?
produced by Aspergillus flavus and A. parasitic. Aflatoxin B1 most hepatotoxic- toxic metabolite is AFB1-8-9-epoxide. Lethal dose 0.5-1mg/kg, levels as low as 0.06mg/kg can be toxic. Median 45d post ingestion, mortality 64-100%.
What is the toxin in sago palms responsible for hepatotoxicity and what part of plan has highest amount?
Cycasin - highest in seeds -> metabolised by gut bacterial enzyme beta-glycosidase to methylazoxymethanol - hepatotoxic, carcinogenic, GI and teratogenic effects within 24-48hrs ingestion, >50% dogs near signs. 32-50% mortality
what cyanotoxins are implicated in blue-green algae toxicity in dogs?
Microcystis aeruginosa or Nodularia spumigena cyanotoxins - released as algae cells diee- disrupt hepatocyte cytoskeleton leading to hepatic necrosis and accumulation of blood in the sinusoids
what is the proposed nephrotoxic agent in grapes? what are the features of toxicity?
Tartaric acid. AKI rare in dogs after ingesting grapes/ raisins/ currants. Amount ingested to induce AKI ranges from 2.8-19.6g/kg , but about 35% of dogs ingesting this amount did not develop azotaemia. Most affected dogs are azoteamic, hypercalcaemic and hyperphosphataemic. 53% survival rate, most surviving dogs had a return to normal renal function.
what are the features of lily toxicity in cats?
nephrotoxic, easter lily intoxication freq fatal, most cats present in the maintenance phase of AKI. Lily toxins are in the aqueous fractions of leaves and flowers, providing potential for dialysis removal but most cats even too late for this. Histopath- acute tubular necrosis. retrospective- only 9% of cats with presumed acute lily exposure became azoteamic after gastric decontamination and 48hrs IVFT.
what are the features of ethylene glycol toxicity?
lethal dose 1.4ml/kg in cats, 4.4ml/kg in dogs- conversion of ethylene glycol to glycoaldehyde by alcohol dehydrogenase is rate limiting step. Other major metabolites include glycolic acid, glyoxylic acid and oxalic acid. Most oxalic acid is excreted in urine; however some may be retained as Ca oxalate. Renal tubular epithelial necrosis causes AKI 2ry to Ca oxalate crystals in tubular lumen. DX- Ca oxalate crystals in urine, or portable tests to identify ethylene glycol in serum. A high anion gap metabolic acidosis is typical due to exogenous anions (glycoxylic acid). 3 phases: 1 hour of exposure- ataxia/ drunk , followed by a relatively asymptomatic period
12-24 hrs postingestion- cardiopulmonary involvement (e.g. CHF)
1-3d later - oliguric AKI, renomegaly, signs of obtundation, anorexia, v+, rank pain, hypothermia, coma, death.
Labs; hypocalcaemia and increased anion gap metabolic acidosis. Some blood gas machines falsely record glycol as lactate, yielding spurious severe hyperlactaemia.
Tx- haemodialysis can remove nearly all absorbed ethylene glycol from blood stream. IVFT may help maintain renal tubular flow. If discovered in early stages, 4-methylpyrazole (4-MP, fomepizole) can prevent metabolism of ethylene glycol by effectively inactivating alcohol dehydrogenase in dogs, preventing formation of oxalic acid and its renal toxicity. Alternatively IV ethanol to competitively inhibit alcohol dehydrogenase - but side effects so 4-MP preferable. Little benefit of 4-MP or ethanol once renal damage has occurred. Px at this stage is guarded to poor.
What are the features of melamine intoxication?
Previous (2007, USA) pet-food contamination with melamine and cyanotic acid - co-ingestion -= insoluble precipitation in renal tubules causes renal failure via physical blockage. Melamine is used in fertiliser and soft plastics. Histpath- intratubular crystalluria , tubular necrosis with regeneration and sub capsular perivascular inflammation. Many died or PTS - those that survived have recovery or improvement in renal function.
More recently Chinse jerky/ sweet potato treats associated with with acquired falcon syndrome, other tubular defects and oligoanuric AKI
what are the features of cholecalciferol (vitamin D3) intoxication?
Vitamin D3 is used as a rodenticide. ingestion results in hypercalcaemia and AKI.
what other body system may be affected with grape/raisin toxicity (other than GI and renal?)
neurological (73% of grape/raisin tax had cerebellum, forebrain or vestibular signs)
