Toxicology Flashcards
What is the MOA of acetaminophen toxicity?
- Reactive oxygen metabolites → oxidative damage to hemoglobin → causes Fe3+ methemoglobinemia and Heinz bodies → hemolysis
- Hepatotoxicity
What diagnostic results would be supportive of acetaminophen toxicity?
- Heinz body anemia
2. Elevated liver enzymes
How is acetaminophen toxicity treated?
- N-acetylcystein
- Cimetidine
- Ascorbic Acid
- SAMe
What are clinical signs associated with acetaminophen toxicity?
- Muddy mucous membranes
2. Anemia
What is the MOA of anticoagulant rodenticide (warfarin, brodifacoum, bromadiolone, etc)?
- Inhibit recycling of Vit K by inhibiting vitamin K epoxide reductase
- Will cause a reduction in factors II, VII, IX, and X
What clinical signs are associated with anticoagulant rodenticide toxicity?
- Prolonged bleeding
- Hemorrhage into body cavities
- Hematomas
- Anemia
What diagnostic findings would be supportive of anticoagulant rodenticide toxicity?
- Prolonged PT then ACT/PTT
How is anticoagulant rodenticide toxicity treated?
- Vitamin K supplementation
- Bioavailability is best by mouth!
What is the MOA of ethylene glycol toxicity?
FIRST PHASE: Causes neuro signs/depression within one hour
- Ethylene glycol → alcohol dehydrogenase (rate limiting step) → Glycoaldehyde
SECOND PHASE: Causes acidosis/cardiopulmonary signs (within 8-24 hours)
- Glycoaldehyde → aldehyde dehydrogenase → glycolic acid
THIRD PHASE: Stone formation (calcium oxalate monohydrate) in 3hrs (cat) and 5hrs (dog); also renal failure (1-3 days)
- Glycolic acid → lactic dehydrogenase/glycolic acid oxidase → glycoxylic acid → glycine, oxalic acid, CO2
What are the main causes of acidoses in ethylene glycol toxicity? What is the most important final metabolite of ethylene glycol?
- Glycolic acid and lactic acid
2. Oxalic acid → cytotoxic to renal tubule and causes Ca precipitation
What are the diagnostic findings associated with ethylene glycol toxicity?
- “Halo” effect on AUS → decreased echogenicity of corticomedullary junction
- Isosthenuria
- AG acidosis
- Hypocalcemia
- Hyperosmolarity
- Crystalluria
What are the clinical signs associated with ethylene glycol toxicity?
- Gastric irritant
2. CNS depression
When should the ethylene glycol test be performed?
- Within 1-12 hours of exposure
- Will not work after 24-48 hours-
- Wont detect <50 mg/dl so it wont work well in cats
What are causes of false positives on the ethylene glycol test?
- Glycerol
- Metaldehyde
- Propylene glycol
How is ethylene glycol treated?
- Ethanol → competitive inhibitor of alcohol dehydrogenase
- 4-MP → competitive inhibitor of alcohol dehydrogenase but doesn’t cause CNS signs like ethanol
- Treatment for acute renal failure
What is the MOA of bromethalin rodenticide?
- Uncouples oxidative phosphorylation → leads to hyper excitability acutely, and then depression chronically
What is the MOA of strychnine?
- Inhibits glycine on motor neurons and interneurons → it inhibits the buffering effect of glycine on post-synaptic motor/interneurons
What clinical signs are seen with strychnine toxicity?
- Extensor rigidity (esp after stimuli) → spastic paralysis also noted
- Respiratory muscle paralysis
How is strychnine toxicity treated?
- Pentobarbital
- Methocarbamol
- Sedation to prevent seizures
- Urinary acidification → with ammonium chloride to help with urine trapping (ionizes the strychnine)
What is the MOA of zinc phosphide? How is it treated?
- Acid stomach contents cause the release of phosphine gas
2. Increase the pH of the stomach (milk of magnesia or 5% orogastric bicarb)
What is the MOA of organophosphates and carbamates?
- Organophosphates: IRREVERSIBLY INHIBIT acetylcholinesterase
- Carbamates: REVERSIBLY INHIBIT acetylcholinesterase
What are the clinical signs seen with organophosphate and carbamate toxicity?
MUSCARINIC EFFECTS:
- Salivation
- Lacrimation
- Bronchial secretion
- Vomiting
- Diarrhea
NICOTINIC EFFECTS:
- Muscle tremors
- Respiratory paralysis
How are organophosphate and carbamate toxicities treated?
- Atropine → anti-muscarinic effects → alleviate severe bradycardia and excessive bronchiolar secretion/constrction → WILL NOT ALLEVIATE NICOTINIC SIGNS
- 2-PAM → act on the OP-Acetylcholinesterase complex to free the enzyme and restore normal function → WILL ALLEVIATE NICOTINIC SIGNS as well as muscarinic → DOES NOT WORK IF ACE IS CARBAMYLATED
What is the MOA of lead toxicity?
- Carried primarily on RBCs*
1. Interferes and competes with Ca ions → also substitutes for Ca in bone matrix
2. Binds to cellular and enzymatic sulfhydryl (thiol) groups
3. Alters vitamin D metabolism
4. Inhibits membrane associated enzymes
5. Inhibit of ferrochelatase and gaba-aminolevulinic acid dehydrates → inhibits heme synthesis
6. GI signs due to alteration of smooth muscle contractility due to interference with Ca dependent mechanisms
What clinical signs are associated with lead toxicity?
- Cats can get lead induced seizures
- GI signs
- Ataxia
- Tremors
- Blindness
- Dementia
- Agression
- Picca
- Vestibular signs
- Megaesophagus (cat)
What are diagnostic findings associated with lead toxicity?
- Anemic (usually not hemolysis though)
- Nucleated RBCs!!!
- “Lead lines” → linear opacities on the physes of long bones
How is lead toxicity treated?
- Must decontaminate before chelation
- CaEDTA! → NOT NaEDTA → NaEDTA will bind CA and cause hypocalcemia
- Succimer → British anti-Lewisite (BAL) analog) → often used in combination with CaEDTA especially when CNS signs present
What is the MOA of xylitol toxicity?
- Causes a rapid dose dependent INCREASE in blood insulin concentration → concurrent DECREASE in blood clues
- Hepatic necrosis can also be seen → secondary to interference with hepatocellular ATP production
How is xylitol toxicity treated?
- First with dextrose supplementation
- Hepatic protectants
- Charcoal is debatable
- Emesis if possible
What parts of lilies are toxic?
- All parts but the flowers are most toxic
What diagnostic findings are associated with lily toxicity in cats?
- Increased BUN
- Increased Creatinine
- Increased Potassium
- Increased Phosphorus
* Creatinine will be disproportionately elevated compared to the increased BUN
What clinical signs are found with marijuana toxicity?
- Depression
- Bradycardia
- Ataxia
- Lethargy
- Vomiting
- Urine dribbling
(Older/Younger) animals are more affected by lead toxicity?
- Younger → more lead absorption following ingestion
What is the MOA of aflatoxicosis?
- Metabolized in the liver by P450 enzymes → reactive intermediates then conjugate with glutathione
- Reactive intermediates result in hepatic necrosis
What are the clinical signs associated with aflatoxicosis?
- Anorexia
- Weakness
- Obtundation
- Vomiting/Diarrhea
- Icterus
- Coagulopathy
What diagnostic findings are associated with aflatoxicosis?
- Increased t. bili
- Liver enzyme elevation
- Decreased albumin
- Decreased protein C
- Decreased cholesterol
What is the MOA of caster bean toxicity?
- Contains the toxalbumin RICIN*
1. Ricin → has a neutral A chain and acidic B chain
2. B-subunit binds to glycoproteins on the surface of epithelial cells and allows the A subunit to enter via receptor mediated endocytosis
3. A subunit then inactivates ribosomal RNA → inhibits protein synthesis → leads to cell death
Which part of the caster bean plant is toxic?
All parts
*seeds have a tough coating that requires mastication but even a very small dose can be lethal
What clinical signs are associated with caster bean toxicity?
- Most commonly there is a 12-24 hours quiescent period from exposure
- Then development of severe hemorrhagic gasteroenteritis
- Other clinical signs may include:
- Hyperthermia
- Vomiting
- Dehydration
- Leukopenia
- Hemolysis
- Hemoglobinuria
- Kidney failure
- Terminal seizures progressing to death
How is caster bean toxicity treated?
- Emesis followed by gastric lavage or charcoal in the asymptomatic patient
- Shock doses of IVF and additional digestive support can be used as indicated by patient condition
What is the MOA of mushroom toxicity?
- Amanita Mushrooms*
1. Contain amatoxins → inhibit RNA polymerases → leads to decreased mRNA generation → arrested protein synthesis → necrosis of metabolically active cells (includes intestinal crypt cells, hepatocytes, and renal tubular cells)
What are clinical signs associated with mushroom toxicity?
6-24 hours after ingestion
- Vomiting
- Bloody diarrhea
- Abdominal pain
24-48 hours after ingestion
1. Severe hypoglycemia caused by insulin release stimulated by alpha-amantin
36-84 hours after ingestion
1. Massive hepatic necrosis and renal tubular necrosis
How is mushroom toxicity treated?
- Silybin → inhibits amatoxin uptake by hepatocytes
What is the MOA of blue green algae toxicity?
- Cyanotoxins microcystin and nodular inhibit serine/threonine protein phoshpatases in the liver → subsequent hyperphosphorylation and disruption of cytoskeletal proteins → leads to hepatic dissociation, hepatic necrosis, and glutathione depletion
How is blue green algae toxicity treated?
- Intensive supportive therapy
2. Cholestyramine can bind cyanotoxins in the gut
What is the MOA of sago palm toxicity?
- The toxin cycasin is activated to methylazoxymethanol by gut bacteria → causes gastrointestinal and hepatic toxicosis
