Lecture 4 Flashcards
What are two hepatic toxins
Acetaminophen
Xylitol
What are renal toxins
Ethylene glycol
Cholcalciferol/vit D3
Grape/raisin
Who is most sensitive to acetaminophen
Cats
What does oxidation of acetaminophen give
NAPQI- highly reactive
Acetaminophen MOA
Formation of NAPQI causes liver tissue necrosis and increased methemoglobin
What is the main problem with acetaminphen in cats
Erythrocyte injury- methemoglobin and heinz body production
Clinical signs of acetominaphen
Methemoglobinemia Hepatotoxicity (dogs get centrilobular hepatic necrosis)
Treatment of acetominaphen
N-acetyl cysteine is gold standard
Abscorbic acid can reduce methemoglobin
Cimetidine can be given to cats but less effective
Antioxidants
Supportive care
Xylitol MOA
Dose dependent release of insulin causing acute liver failure from depleted cellular ATP levels
Clinical signs of xylitol
Vomiting, lethargy, ataxia, collapse, seizures
May see elevated liver enzymes and coagulopathies
What should you differentiate xylitol from
Hypoglycemia, acetaminophen, aflatoxins
Treatment of xylitol
Activated charcoal NOT recommended because it doesn’t bind xylitol well
Monitor blood glucose and liver function- can give dextrose
Why is the kidney a common site of toxicity
High blood flow
High concentraion of toxins
Critical for excretion of foreign substances
Where in the kidney is the most common site of toxin induced injury
Proximal convoluted tubule
Describe acute renal failure
Decreased GFR and azotemia
Caused by transient damage to tubule, glomerulus, or vasculature
Signs are vomiting, GI bleed, PU/PD, anuria, diarrhea, tremors
Describe chronic renal failure
Will see edema, hypocalcemia, parathyroid activity, anemia
Ethylene glycol MOA
Metabolizes to
Glycolic acid which causes acidosis
Glyoxylic acid which causes CNS signs
Oxalate/oxalic acid which causes renal damage and hypocalcemia
Stage 1 clinical signs of ethylene glycol
30 min to 3 hours
Drunkeness, ataxia, CNS depression
Nausea vomiting
PU/PD
Stage 2 clinical signs of ethylene glycol
12 to 24 hours
Tachypnea, tachycardia or bradycardia
Cats usually just remain depressed
Stage 3 clinical signs of ethylene glycol
12-72 hours Most animals present in this stage Polyuria progressing to anuria Lethargy, anorexia, seizures Oral ulcers, abdominal pain, dehydration, enlarged kidneys
Diagnosing EG toxicity
Measure EG in blood Azotemia Low urine SG Calcium oxalate crystals in urine and kidneys Hyperglycemia Hypocalcemia High anion gap and high osmolal gap
Treatment of EG
Prevent formation of metabolites with ethanol and sodium bicarb
Fomepizole
*contraindicated in animals with renal failure and pointless in animals if it has already metabolized
What should you treat cats with EG to survive? What about dogs?
Cats- 3 to 4 hours
Dogs- 6 to 8 hours
Cholecalciferol MOA
Causes increased Ca by Increasing GI absorption Decreasing renal excretion Increasing synthesis of Ca binding proteins Mobilizing bone calcium
Clinical signs of cholecalciferol
Anorexia, weakness, depression,
Thirst, polyuria
Diarrhea, dark feces from intestinal bleeding, vomiting
Hypertension, bradycardia, ventricular arrhythmia
Mineralization of tissues
Diagnoses of cholecalciferol
Increased P, Ca, BUN, creatinine,
Low PTH, urine SG with calciuria
High hydroxycholecalciferol levels in bile and kidney
What should you differentiate cholecalciferol from
Paraneoplastic syndrome, juvenile hypercalcemia, hyperparathyroidism
Treatment of cholecalciferol
GI decontamination
Fluids and furosemide
Prednisone to reduce renal calcium resorbtion and GI absorption
Pamidronate as calcitonin
MOA of grapes and raisins
Unknown
Clinical signs of diagnosis of grapes and raisins
Vomiting followed by renal failure
Increased Ca, P, and azotemia
Treatment of grapes and raisins
Emesis, lavage, activated charcoal
Fluids
Other supportive care
