Enviromental/Toxocology Flashcards
What is the MOA of Fenoldapam
Selective dopamine -1 receptor (DA-1) agnoist
Induces vasodilation and selectively increases renal cortical and outer medullary blood flow and GFR
JVIM 2018 Fenoldapam for the prevention of AKI with heat stroke
No difference in AKI in heatstroke with or without fenoldapam
JVECC 2017 What hemostatic abnormalities were found in naturally occurring heatstroke
No difference in any parameters at presentation
Non survivors: prolonged PT @ 12 hrs, decreased TPCA @ 12 hrs, Increased PTT @ 12/24 hrs; Lower fibrinogen at 24 hrs
Mortality 40%
Define heatstroke in dogs
Rectal temp > 105.8F
Leads to endothelial injury neutrophilic infiltration, widespread cellular apoptosis, microthrombi and hemorrhagic diathesis
JVIM 2019 AMiodarone and itraconazole for treatment of trypanosomiasis in dogs
Improved survival with treatment for 12 months
JVIM 2019 What is the MOA for amiodarone and itraconazole for the treatment of trypanosomiasis in dogs
Antifungals: T.crui and fungi share similar pathways for biosytnethsis of sterols
Amiodarone disrupts the calcium homeostasis in T. Cruzi; blocks critical protease cruzipain and inhibits production of sterols
JVECC 2017 What were the main toxicity of topical flurbiprofen exposure in a cat
AKI, anemia, and gastroduodenal peforation
JVECC 2017 what treatment was used for oleander toxicity in dogs
Digoxin specific antibiody fragments (digifab)
What is the MOA for oleandar toxicity
Structually similar to digitalis.
Inhibits the Na/K atapse by inducing a conformational change
Which toxins are likely to be removed by TPE
Low Vd and highly protien bound likely to be removed with TPE
JVECC 2017 (2 articles) and JVIM 2019 Which NSAIDS have been reported to be used with TPE
Meloxicam, Ibuprofen, naproxen, dericoxib
JVECC 2017 What signs are anticipated with Inocybe mushroom ingestion and why
SLUDD- most common vomiting
Mainly parasympathetic effects as acts on muscarine
JVAMA 2017 What is isoniazid and how does it work
Anitmycobacterial useful for tuberculosis
Results in pyridoxin depletion
Poorly protien bound with small v/d
JAVMA 2017 What incrased survivial in dogs with isoniazid toxicity
Increased body weight and IV administration of pyridoxine (dose 1:1)
Decreased survival with increase dose and seizures
JVECC 2017 What is single pass lipid dialysis
Using 5% lipid in diaslyte used for highly lipohilic toxins such as ivermectin and baclofen
Can use same mechanism with albumin for highly protien bound
JVECC 2017 what is the MOA of ivermectin toxicosis
Binding results in GABA gated chloride channels in the CNS, leading to membrane hyperpolarization and blockade of neural impulses.
What is the MOA of loperimide
Lipid soluble pure Mu opiod agonist. Dosenth have analgesic or sedative effects because P-glycoprotie mediated efluxx prevents its accumulation in CNS
What is the treatment for loperimide toxicity and which patients may have issues
ABCB1 mutation
Naloxone, time, interlipids
What are adverse effects of intralipids
Lipemia, triglycerides, Pancreatitis, if extravasation- pain @ infusion site,
People- anaphylaxis
JVECC 2018 What were the signs of metformin toxicity in a dog
Severe hypoglycemia and hyperlactemia
Which toxins are best removed via hemodialysis
Low molecular weight, low Vd, low protein binding
Which toxin characteristics benifit from hemoperfusion in addition to hemodialysis
Larger size > 1500 Daltons, and increased protein binding
JVECC 2018 Which extracorpeal toxin removal method would you use for cyclosporine and why
HD + HP; due to high Vd and MW of 1200 Da
What is the MOA of Minoxidil
ATP sensitive potassium channel opener with potent vasodilatory effects
JAVMA 2018 What is th treatment for minoxidil
with mostly alpha adrengic agonists and avoid Beta to not increase cardiac O2 demands
What is the MOA of ionophores
Influx of Na and CA leads to intracellular Ca overload
Respiratory failure
JVECC 2018 Which extracorpeal toxin removal method would you use for methotrexate toxicity
HD + charcoal HP
JVECC 2018 What are teh side effects of rapid administration of undiluted levetiractam
Tachycardia, hypergycemia, hypotension
Improved with Epinephrine
JVECC 2019 Which extracorpeal toxin removal method was used for cannabinoid toxicity despite what characteristics of THC
HD + HP
Shown effective for THC in people as it causes withdrawals
THC is lipophilic and highly protein bound
What is the MOA of organophsophate toxicosis
Inhibits acetylcholinesterase by binding to esteric site.. Leads to build up of ACh in synaptic cleft
What signs/acronyms due you see with acute muscarinic
SLUDD: Salivation, lacrimation, urination, diarrhea, dyspnea
DUMBELs: Dyspnea/diarrhea, urination, miosis, bradycardia, emesis, lacrimation, salivation
What is the response to a test dose of 0.02 mg/kg of atropine that rules out organophate toxicity
mydrasis and tachycardia
What is the treatment for organophosphate toxcitity
2PAM: pralidoxime chloride
Reverse initial ionic binding of organophosphates to AChE
Must be given in timely fashion, but may still see improvements at 72-96 hrs
JVECC What is the mechanism and signs of chlorfenapyr
insecticide that uncoupler of phosphorylation
Peracute fever, neuro signs, GI signs
JVECC 2019 Activated charcoal with sorbital showed what changes in electrolytes with water restriction
Increase in Na, K, CL and lactate, calculated osmolality
Significant weight loss.
Hyper Na attributed to dehydration
JAVMA 2019 What is the MOA and signs anticipated with duloxetine toxicity in dogs
Seritonin and nor-epinephrine reuptake inhibitor
Trembling, lethargy vomiting, mydrasis…. seritonin syndrome
JVECC 2019 What are the signs with barium nitrate toxicity
flacid pralsyis with fasiculations
Acidemia and severe hypokalemia
JVECC 2019 What dose of mannitol and what were the signs that were noted with toxicity
6 g/kg over 24 hrs:
AKI with hypertonic hyponatremia with renal tubular dysnfuction
High osmol gap as mannitol is an unmeasured osmol
JVECC 2019 what type of toxicity was noted with cheese tree root and where
Australia
ALF
JVIM in evaluation of TPE for NSAID toxicities what was noted to increase length of hospitalization
Decreased PCV at presentation
JVECC 2019 What is the MOA of eastern coral snake envenimation and what was the outcome with MV
Good outcome 7/8 survived 58 hrs MV regardless of antivenom
Alpha neurotoxins that competively block post synaptic nicotinic acetycholine receptor site
See diffuse LMN weakness–> paralysis –> Death from Resp failure
JVECC 2019 Define serum sickness and what was it noted with
antivenom
Type III hypersensitivity reaction that is delayed generally 1 week (1 day to months)
Fevere, puritis, ecchymosis, uticaria, arthralgia
What are the proposed MOA of ILE
Improved mycoardial performance: Free fatty acids to myocardium as preferred substrate; FFA stimulate voltage gated calcium channels
Lipid sink: Log P > 1.0 pulls toxins from CNS and heart back to plasma
What dose is recommended for ILE
Not to exceed 10 ml/kg/day of 20 %
1.5 ml/kg IV bolus folled by a .25-0.5 ml/kg/min fur 30-60 minutes
What properties are needed for toxin removal with hemodialysis
< 500 Daltons, moderate to large Vd, minimal protein bidning
Ex: EG, Enrfoloxacin, barbituates
What properties are needed for toxin removal with hemoperfusion
Charcoal needs to have high affinitinity and moderate to large volume of distribution
Size and protein binding do not affect
What toxins work well with HD/HP
NSAIDs, phenobarb, cafiene, theobromine, and vincristine
what properties are needed for toxin removal with aphresis (TPE
small volume of distribution
Efficacy unaffected by protein binding or size
amanited, Vincristine, NSAIDs
What type of kidney damage is caused by grape/raisins/currants
severe renal tubular degeneration, protein/cellular debris obstruction of the tubules
What type of kidney injury is caused by lily toxicant
Proximal tubular epithelial necrosis edema, tubule obstruction
pancreatitis is also observed
What is the MOA of anticoagulant rodenticides
inhibit physiologic vit K recycling inhibiting vitamin K epoxide reductase in the liver
Protein C decreased earliest clinical indicator
What is the MOA of neurotoxic rodenticide
Bromethalin- neurotoxin that uncouples oxidative phsophorylation, decreasing ATP production
Undergoes enterhepatic circulation
What is the MOA of cholecalciferol rodenticides
Cholecaciferal convered to calcitriol in the kidney
Results in increase Ca and Phos absorption from Gut, bone and kidneys
What calcium phosphorus ration = mineraliztion
> 60 mg/dl
What is the treatment for cholecalciferol rodenticides
cholestyramine 0.3-1 gram/kg PO q 8 hrs
What is the pathophys of heat stroke
Initially have increased CO due to peripheral vasodilation and decreased SVR
Peripheral and splanchnic blood pooling and dehydration lead to hypovolemia
Leads to decreased CO and failure of heat loss mechanisms of radiation and convection and increased temperature
What are serious complications of Heat stroke
Rhabdomyolysis, AKI, ARDS and DIC
What are risk factors for Heat stroke
Prior occurance; obesity, Breed (golden, lab, brachycephalic), Body weight > 15 kg; Increased environmental temp/humidity; lack of acclimation/fitness
What is the heat shock response
Rapid molecular cytoprotective mechanism that involves production of heat shock proteins (HSP 72)
increase in HSP 72 improves cytoprotection
What bloodwork abnormalities have been previously associated with increased mortality in heat stroke
Nucleated RBCs > 18/ 100 wbcs
Increased ALP & GGT
Hypoglycemia
What is the MOA of Bufo toad toxicity
biogenic amines (epi/norepi) cause hallucinogenic or CNS signs Steroid derivatives- digitalis like toxin
What is ethylene glycol’s metabolism
EG –> + Alcohol dehydrogenase –> Glycoaldehyded (CNS Signs) –> + aldehyde dehydrogenase –> glycolic acid (metabolic acidosis, increased anion gap and AKI) —> gllyoxilic acid —> oxalic acid (AKI), Glycen, and alpha hydroxy beta ketoadipate
Which of ethylen glycol’s metabolites cause injury
Glycoaldehyde CNS signs
Glycolic acid: Metabolic acidosis, increased anion gap, and AKI
Oxalic acid: AKI
How quickly do you see changes in osmol gap and anion gap in EG toxicity
osmol gap 1 hr
anion gap 3 hrs
In EG toxicity what might a POC lactate be high
Increased lactate is really the metabolite glycolate
lactate level is normal
What is the gold standard diagnostic for ethylen glycol
Gas chromatography
What are tests in hospital that can be run to test for Ethylene glycol
Woods lap for dye in some products of urine, mouth, and paws. Only in urine for ~6 hrs
Kacey EG test strip for plasma: Lower limit is 20 mg/dl which is lethal dose for cats. Fals postiives with alcohol for blood draw, and propylene glycol
React eG: bust be read within certain time frame, and high false positive
Slide for some chem machines: does not cross react with propylene glycol
What are the treatments for ethylene glycol
4MP (fomepizole)- inhibits alcohol dehydrogenase
ethanol- competiviely binds alcohol dehydrogenase
What are the negative side effects of the ethylene glycol treatments
4MP: CNS depression, anaphylaxis with second dose
Ethanol: Worsening ataxia/neuro signs, polyuria–> dehydration
What properties of Ethylene glycol make it suitable for HD
Low molecular weight and low protein binding of EG and metabolites, good throughout course