Ethylene Glycol/Propylene Glycol/Ethanol-Methanol Flashcards
Main use of ethylene glycol
antifreeze
Main source of exposure of ethylene glycol
ingestion of antifreeze
Toxicokinetics of ethylene glycol
rapidly absorbed from GIT - delayed by food
rapidly distributed to all tissues including CNS
metabolized to toxic metabolites in the liver
oxidized by alcohol dehydrogenase to glycoaldehyde –> oxidized by aldehyde dehydrogenase to glycol acid –> oxidized by aldehyde dehydrogenase to glycoxylic acid, glycine, formic acid, hippuric acid and benzoic acid
oxalic acid binds to serum calcium to form insoluble calcium oxalate crystals (monohydrate) and hypocalcemia
MoA of ethylene glycol toxicity
ethylene glycol - direct GI irritation, increased serum osmolality (osmotic diuresis), CNS depression
toxic metabolites - cause metabolic acidosis and acute renal failure
Ethylene glycol and acute renal failure
metabolites are cytotoxic to renal tubular epithelium
calcium oxalate monohydrate crystal formation within renal tubules contributes to damage
crystals adhere to cellular membranes, internalized by cell and alter cellular structure and function, increase reactive oxygen species and produce mitochondrial dysfunction
Early signs of ethylene glycol toxicosis
EG effects and systemic acidosis
nausea, anorexia, CNS depression, ataxia, incoordination, hypothermia, muscle fasciculations, tachycardia, tachypnea, PU/PD, dehydration, coma, death
T/F: cats with ethylene glycol toxicity usually show polydipsia
false
Late signs of ethylene glycol toxicosis
oliguric renal failure
vomiting, anorexia, depression, severe lethargy, coma, seizures, oliguria, renal pain
Ethylene glycol lesions
Gross - hemorrhagic gastroenteritis, pulmonary edema, pale and swollen kidneys with grey or yellow streaks
Microscopic - yellow birefringent rosette shaped calcium oxalate crystals in the kidney or urine
Lab diagnosis of ethylene glycol toxicosis
large anion gap, increased serum osmolality
hypocalcemia, hyperglycaemia, acute renal failure changes
increased PCV and total protein
calcium oxalate crystals in urine sediment
causes false positive on a KaceyTM EG test
ethanol, propylene glycol, mannitol, sorbitol, glycerol
T/F: Catachem ethylene glycol test can be falsely positive due to ethanol
false
Treatment of ethylene glycol toxicity
detoxifcation
specific antidote - inhibitors of alcohol dehydrogenase
fomepizole (best)
ethanol 20% - higher affinity for alcohol dehydrogenase than EG
supportive therapy - sodium bicarb for acidosis
fluid therapy - IV 5% dextrose in half strength saline
T/F: dogs and cats are commonly intoxicated by ethanol/methanol
false, its rare
T/F a diet with a very high glucose level (18-60%) can cause ethanol toxicosis
true, due to yeast fermentation inGIT
Toxicokinetics of ethanol/methanol toxicity
readily absorbed orally, food in stomach delays absorption
widely distributed to CNS
ethanol metabolized by hepatic alcohol dehydrogenase to acetaldehyde –> acetate –> acetyl CoA –> CO2 and water
MoA of ethanol/methanol toxicity
irritates mucus membranes CNS depression acetaldehyde is vasodilator and induces vomiting acetate causes metabolic acidosis ethanol inhibits ADH causing diuresis
Signs of acute ethanol/methanol toxicosis
Rapid onset of CNS depression abnormal behaviour vomiting hypothermia, tremor and ataxia congested MM PU/PD death from resp failure
Lesions associated with ethanol/methanol toxicosis
congestion of GI mucosa, liver, kidney and lungs
Treatment for ethanol/methanol toxicosis
no specific antidote for ethanol, ethanol and fomepizole for methanol
emetics if recent ingestion
activated charcoal not effective
supportive and symptomatic therapy
Main use of propylene glycol
antifreeze (“safe”)
source of exposure of propylene glycol
accidental ingestion in small animals
giving instead of mineral oil in horses
Toxicity of propylene glycol
dogs, cats, cattle and horses susceptible
cats more sensitive
safer than ethylene glycol
Toxicokinetics of propylene glyco
rapidly absorbed from GIT and inhalation
metabolized in liver by alcohol dehydrogenase to lactaldehyde –> lactic acid (D and L isomers) –> pyruvic acid
Which of the following is FALSE regarding the toxicokinetics of propylene glycol?
A) High concentrations of D-lactic acid may cause lactic acidosis
B) L-lactic acid is used by the TCA cycle
C) propylene glycol is partly excreted in the urine
D) propylene glycol is metabolized in the blood
D - propylene glycol is metabolized in the liver
MoA of propylene glycol
not metabolized to toxic metabolites osmotic diuresis CNS depression D-lactic acid may cause encephalopathy Heinz body anemia in cats
Clinical signs of propylene glycol
signs due to narcotic effects and acidosis
ataxia and CNS depression
Heinz body anemia in cats
muscle twitching in cats
Lab diagnosis of propylene glycol
metabolic acidosis hyperosmolarity increased anion gap from lactic acid hypoglycaemia seen low urine SG Heinz body anemia in cats
Treatment of propylene glycol
emesis and activated charcoal - questionable efficacy
supportive tx - IV fluids and bicarbonate therapy
metabolism inhibitors not required
