Toxicology - Exam 2 Material Flashcards
(38 cards)
Regarding copper toxicity, what are the hisotlogical lesions that youre gonna see?
- Tubular nephrosis, acute , multifocal, severe with hemoglobin casts
Gastroenteritis
**Hepatocellular necoris, acute, ** multifocal severe
Regarding copper toxicity,
- what are some different sources for food animals?
- Which animals are affected?
1) dietary imbalance
2) A) Sheep (this spp is most sensitive) and note that the exposure is CHRONIC B) THIS IS AN AUTOSOMAL RECESSIVE DISEASE IN DOGS –> COPPER STORAGE DISEASE
3)
What is the mechanism of action for copper toxicity?
- oral –> chronic exposure but abrupt onset
- Excess copper stored in the liver; note that Cu-Mo-S are excreted in the bile; and lysosomes (function to ???)
- Liver has high storage capacity/reach capacity + stress
Cu released –> hepatocellular necrosis –> serum Cu –> hemolysis (most the time)
Discuss the clinical pathology for copper toxxicity
- Liver enzymes –> elevated GGT and AST
- Anemia due to hemolysis
- Hemoglobinemia/uria, hyperbilrubinemia/uria
- Methemoglobinemia (brown blood)
Regarding copper toxicity, discuss treatment/prevention
Prognosis: guarded - poor for lcinically affected animals (both small animals and large animals)
Treatment + prevention: enhance copper excretion (FA):
- **Mo-S source: enhances feceal, urinary, biliary excretion/slows down absorpption and enhancs excretion
- Chelators –> Decrease body burden
Discuss copper storage disease (chronic active hepatitis) for canines and treatment for it
Chronic accumulation!
- Not excessive in diet
- Autosomal reccessive –> seen in Bedlington terrier breed and sometimes in West Highland white terriers
Chronic bouts of intermittent hepatti
Treatment –> Penicillamine (chelator that reduces body burden and zinc acetate (reduces absorption long term); treatment is usually long tterm
Regarding cyanobacteria, discuss the basics of it
- Targets the liver and CNS
- Criteria about charcteristics where these algal blooms are found –> 1) ubiqitoud 2) stagnant-slow moving 3) decreased oxygen, 4) increased nutrients (phosphates, nitrates and sulfates), 5) quiet weather 6) warmish water - Temperature and pH (?????) 7)high light intensity
Discuss the mechanims of action for cyanobacteria
All species suscpetible
Microcystin/nodularin/cylindrospermopsin - specific to the liver
- Massive necrosis with hemoorhage
- Cylindrospermopsin - renal necrosis
- cylindrospermopsin also affects the kidneys
Shock –> DIC –> Death
Discuss clinical isgns associated with cyanobacteria
Clinical signs are liver specific
- elevated ALT, bile acids, bulirubinemia/uria and prolonged PT-PTT
- low albumin, low protein, low BUn, cholesterol
- Potential renal changes
Discuss the basics of anticoagulant rodenticide toxicity
- All species are sueceptible except for cats, carts are pretty resistant to it.
What is the mechanims of action for Anticoagulant rodenticide toxicity
- Vitamin K is an essential cofactor in actiavtion of clotting factors II, VII, IX, X. When rhis occurs, ‘active’ vitam,in K –> inactive vitamin K epoxide
- **Vitamin K epoxide reductase
- Rodenticdes inhibit enzyme –> prevents recycling ‘active’ vitammin K**
- Loss of clotting factors, therefore we are likely going to see prolonged clotting times
Regarding anticoagulant rodenticide toxicity, what are the clinical signs?
- Onset: 2-3-5 days; clotting prolongation occurs erlier but after 36-48 hours, we start seeing a delay when 65-80% of factors are lost)
Treatment is dependent upon: hemorrhage site, speed, and volume. HEMORRHAGE CAN OCCUR ANYWHERE
- 70% BLEEDING INTO THE LUNG, THORAX, AND MEDIASTINUM
Discuss diagnosis criteria for anticoagulant rodenticide toxicity
- History of use/exposure: Assume long acting
- Clinical pathology, clinical signs: site, volume, speed of hemorrhage
DO NOT RULE OUT IF OATIENT IS NOT ANEMIC … prolonagtion of clotting times occurs before anemia is seen
Reememebr, it is important to differentiate between 1) loss vs 2) hemolysis vs 3) lack of production
DO NOT LIST MALABSORPTION AS AN ANSWER ON THE EXAM
For clotting pannel, expect prolonged PT and PTT
Discuss the treatmnent for antiocoagulant rodenticide toxicity
1) do the math!!!! if the dose is NOT TOXIC, send the animal home
2) Toxic dose: establish baseline clotting panel
**A) Decontaminate **
B) Plasma/blood transfusions if needed
C) Vitamin K1
Think about decontamination several hours post ingestion, then most likely you are gonna wanna administer Vitamin K1. If you have a patient that vomits after you administered activated charcoal, then you MUST ADMINISTER THE FIRST DOSE SUB-Q. Treat for 4 weeks too. After 4 weeks therapy, you must wait 36 - 48 hours before checking the clotting times to see if they’re still clapped or not.
Regarding NSAIDs, what is a prostaglandin?
A prostaglanding is a lipid derived chemical messemnger mostly acting in a paracrine fashion which means they act on the site where they are released
What are the actions of NSAIDs?
- NOte that these actions result from the inhibition of prostalglkandinng synthesis
1) Anty-inflkammatory (COX-2)
2) Antip-pyretic (COX-3) –> this means that it functiona to reduce fever
3) Analgesia (COX-2)
4) Gastric ulceration (COX-1)
5) Reduced renal blood flow
6) May interefere with parturition
7) Inhibition of platelet aggregatuon
8) COX2 and the heart
9)
With regards to the actions of NSAIDs and specifically, the action of NSAIDs that inhibit platelet aggregatuion
1) Why is aspirin significant?
2) Why is warfarin significant?
3) Acetominaphen –? why is it significant?
1) Aspirin has an irreversible action
2) Warfarin –> warfaroin has the potential for drug interactions; warfarin also acts as an anticoagulant which is signifiant because warfarin also competes with many NSAIDs for binding to plasma proteinS
With regards to cantharidin toxicity, what species is most susepctible to this? Next, discuss its mechanism of action
Cantharidin is a toxin that comes from beetles; the most suspectible species to this toxin is horses then cows.
Mechanims of action:
- lipid solubvle/highly irritating –> penetrates and causes acantholysis
- - readily absorbed, the majority of it is excreted in the the urine uchnaged
- Hypocalcemia/hypomagnesemia
Regarding canthariding toxicity, discuss the clinical pathology that is expcted
Next, discuss the gross and histologic lesions
Clinical pathology:
- decreased Calcium and decreased magnesium and an inflammatory leukogram
1Gross lesions: **Congestion, inflammation, hemorrhage GIT + renal system*
Histologic lesions: Gastroenteritis, nephritis, cystitis, myocardial necoris
mnost importantly –> look for the vesiculation of the nonglandular portion of the gastric mucosa
Discuss the toic of dryer sheets and cationdtergents along with treatnment:
- Cationic detergents **toxicity related to concentration + pH (<3 or > 11): GIT inflammation and necrosis: caustic/corrosive
- Treatment: options include: treat the patient (sympotmatic)
- Most important GI protectants are: analgesics, anti inflammatoryies, PEG tube, endoscopy, antibiotics, other symptomatic care
Discuss the topic of cationdetergents
Includes fabric softeners, germicides, sanitizers, dryer sheets, pot-pourris –> quarternary ammonium compounds with groups attached
- Highly to extremly toxic –> corrosoive effect of concentration
- Solutions > 1% can be corrosive
- Oral ingestopn –> salivation, vomiting, muscle weakness and fasiculations, CNS + respiratory depression, fever, seizures, colllapse, coma
Treatment:
- milk, water, or egg whites
- follow with AC + cathartic
- esophagoscopy
- Maintain fluid and electrolyte balance
-
Discuss the topic of acetominaphen
Discuss the topic of acetomenaphen and over exposure (what happens to the methabolic pathways):
- **analgesic, antipyretic ** - some anti inflammatory (inidicatioons that it does inhibit cyclooxygenase-COX2)
Toxicity:
- Cats –> extremely sensitive (ferrets are also sensitive)
DE TOX PATHWAYS **(GLUCOURONIDATION/SULFATION-MORE SATURABLE IN CATS) ** BECOME OVERLOADED –> more acetominaphen to reactive intermediate (RI) –> glutathione supply is depleted –> **RI ** responsible for hepatic necoris and red blood cell lysis/methemoglobin
Discuss the clinical siogns associated with cats ingesting acetomenaphen and the clinical pathology that should be exopected
- Delay in onset
- CATS: primary target is RBC (increased dose, more likely to see liver)/ secondary target is liver/ third most important target is kidney/hypoxia)
- **Methemoglobin, ** , heinz bodies, **hemolysis, **, hemoglobinuria/emia
- Liver necorsis leads to: salivation, vomiting, aabdominal pain, anorexia
- Brown blood/mucous membranes can be white or cyanotic or muddy or icteric
- Facial paw edmema
Discuss acetomenaphen ingestion in cats and the expected clinical signs and clinical pathology
- Delay in onset
- DOGS: primary target is liver, secondary target is RBC, third most important target is kidney (hypoxia)
- Liver necrosis –> disease, failure: anorexia, vomiting, depression-lethargy, abdominal pain –> icterus, weight loss (elevated liver enzymes-bile acids and decreased protein, clotting pronlems, etc)
- **RBC ** –> **milder methemoglobinemia, hemolysis ** leading to hypoxemia, hypoxia: weakness, letargy, cyanosis, tachypnea,
- Death due to hypoxia and/or liver failure
- Facial paw edema
- **Blood is brown/mucuous membranes can be white or cyanotic or muddy or icteric **
