5-Cardiovascular and Hematopoietic Toxicity Flashcards
Anticoagulants and anticoagulant rodenticides
Oral anticoagulant therapy and anticoagulant rodenticides discovered 1920s due to moldy sweet-clover poisoning of cattle
Widely used products
- 1st generation (warfarin)
- short half life (15 hours)
- Low potency (multiple feedings required)
- LD50=10-50 mg/kg
- 2nd generation compounds (brodifacoum)
- long half life (20 days)
- High potency = kills in single feeding
- LD50 = 0.25 mg/kg
Anticoagulants
MOA
Inhibits Vitamin K1 epoxide reductase
Prevents formation of Vit. K dependent clotting factors
- II, VII, IX, X
anticoagulant rodenticide
Clincial signs
Delayed onset (3-5 days)
Initial signs
- depression
- anorexia
- anemia
Dyspnea, nosebleeds, bleeding gums, bloody feces
Hemorrhage
anticoagulant rodenticide
DX
- History of exposure
- Evidence of coagulopahty
- Response to vitamin K1 therapy
Hematological tests (>25% longer times with normal platelets can be ind of tox)
- inc prothrombin time (PT)
- inc activated partial thromboplastin time (APTT or PTT)
anticoagulant rodenticide tox
TX
Recent exposure (few hours)
- Emetic, absorbent, cathartic therapy
Vitamin K administration
- continue for 10-14 days (warfarin)
- 30 days for 2nd gen
Severe cases
- transfusion
Nitrate toxicosis
Fertilizers, water contamination, many plants
- Lambsquarters
- Black nightshade
- Pigweed
Converted to nitride
- vasodilation
- oxygen starvation: methemoglobin
Susceptibility: Pigs > cattle > sheep > horses
Nitrate tox
Clin signs
Levels of metHb
- <10% asymptomatic, may see membrane color changes
- ~15% : cyanosis, brown blood and MM
- 50%: serous toxicity, seizures, coma
- > 70% death
Diagnose by nitrate levels in feed or water
Suspected nitrate deaths
- save an eyeball for analysis
- also plasma and serum
Nitrate tox
Treatment
Methylene blue 1-2%
- Most effective in ruminants
- Urine with become dark greed
Horses and cats: ascorbic acid
Educate farmers and ranchers
- nitrate accumulation in weeds and forages intended for feeding/grazing
- Heavy use of fertilizers
- unkempt pastures
- drought
Can feed cattle corn to inc nitrite reduction by rumen flora
Cardiac glycosides
Inhibits sodium-potassium ATPase pump, competition with potassium for binding sites
Plants:
- Lily of the valley
- Oleander
- foxglove
Cardiac glycosides
Clinical signs
Clinical signs
- Can occur from 1hr to 3 weeks after ingestion
- Grazing animals
- trembling, staggering, dyspnea
- Inc in Ca and intracellular Na
- Racing heart, arrhythmia, weak pulse
- hyperkalemia (K+ can double)
Cardiac glycosides
Diagnosis
Based on history
Access to plants
Clicial signs
Analysis of vomit
Cardiac glycosides
TX
Recent exposure
- GI decontamination
Arrhythmias
- propranalol (Beta blocker)
Treat hyperkalemia
- furosemide
- insulin
- sodium bicarb
- chelators
Digoxin if propranolol is ineffective
- EXPENSIVE
- antidote for digoxin and similar glycosides
- binds directly to glycosides
- complete resolution of clinical signs within 4h
Cyanide toxicity
about
MOA
Consumption of wilted leaves and seeds
- wild cherry
- white clover
- fresh sorghum spp
fertilizers
Non toxic when dry, volatile as hydrogen cyanide
MOA: inhibition of cytochrome oxidase
*can cause sudden death
*wear respirator if you suspect
Cyanide tox
Clinical signs
Clinical signs
- occur within 15-20 min to a few hours after consumption
Classic symp
- cherry red blood, slow to clot
May smell almonds in stomach contents
Sudden death, dyspnea, weakness, tremors
Cyanide tox
DX
Cherry red unclotted blood
Analysis of frozen stomach contents
- prevents cyanide from volatalizing
Cyanide tox
TX
Two steps
- Induce methemoglobin
* sodium nitrite binds to cyanide - Give sodium thiosulfate to inc formation of thiocyanate by rhodanese
- sulfur donor
- thiocyanate is non-toxic and eliminated
Vitamin B-12
Cobalt
If necessary treat metHb with methylene blue
Methylxanthines
Caffeine, theobromine, theophylline
Chocolate, coffee, and meds
- Unsweetened baking chocolate ext toxic
- Caffeine tabs in race horses
- Cocoa bean mulch for horses
Occurs around holidays
Methylxanthines
MOA
Competitive antagonist of adenosine receptors
- causes CNS stimulation, vasoconstriction, tachycardia
Prevents Ca reuptake
- leads to inc skeletal muscle and cardiac muscle contractility
Inhibits phosphodiesterase
- increases cyclic AMP and GMP concentrations
Methylxantines
Clinical signs
Vomiting, diarrhea, diuresis
Hyperativity
Panting
Tachycardia, hypertension
Ataxia
Tremors, seizures
Coma
Death from arrhythmias or resp failure
Gossypol
- Found in pigment glands of cottonseed
- provides insect resistance to plant
- Levels vary with preparation and type of cotton
- inactivated by heating
- affects many organ systems
- high level of energy, protein, and effective fiber
Gossypol
MOA
- Chronic toxicosis
- Plasma gossypol increases with time
- half-life 4-5 days
- can be cumulative
- lipophilic
- Chelates iron, causes anemia, reduces protein availability
- Produces toxicity by inhibition of dehydrogenases
- leads to decreased energy and protein production
- oxidative stress
- Non ruminants more sensitive, except horses
Gossypol Toxicity
Clinical signs
- usually with longterm feeding
- Lower concentrations
- weigh loss
- weakness
- dyspnea
- Moderate anemia possible
- congestive heart failure
- edema secondary to heart failure
- myocardia necrosis
- Dairy cows and lambs may die suddenly with minimal lesions
- Repro effects
- decreased sperm production
Gossypol
Diagnosis
- diagnose by history of ingestion of cottonseed
- cardiac decrosis, edema, vacuolization
- chemicaly analysis of gossypol
- ddx
- pale muscles also ionophores
Gossypol
TX
- remove cottonseed
- feed high protein diet
- vitamin a
- iron and lysine
- gossypol binds to lysine
- symptomatic treatment
