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Toxicology > 5-Cardiovascular and Hematopoietic Toxicity > Flashcards

5-Cardiovascular and Hematopoietic Toxicity Flashcards

1
Q

Anticoagulants and anticoagulant rodenticides

A

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
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2
Q

Anticoagulants

MOA

A

Inhibits Vitamin K1 epoxide reductase

Prevents formation of Vit. K dependent clotting factors

  • II, VII, IX, X
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3
Q

anticoagulant rodenticide

Clincial signs

A

Delayed onset (3-5 days)

Initial signs

  • depression
  • anorexia
  • anemia

Dyspnea, nosebleeds, bleeding gums, bloody feces

Hemorrhage

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4
Q

anticoagulant rodenticide

DX

A
  1. History of exposure
  2. Evidence of coagulopahty
  3. 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)
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5
Q

anticoagulant rodenticide tox

TX

A

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
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6
Q

Nitrate toxicosis

A

Fertilizers, water contamination, many plants

  • Lambsquarters
  • Black nightshade
  • Pigweed

Converted to nitride

  • vasodilation
  • oxygen starvation: methemoglobin

Susceptibility: Pigs > cattle > sheep > horses

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7
Q

Nitrate tox

Clin signs

A

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
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8
Q

Nitrate tox

Treatment

A

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

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9
Q

Cardiac glycosides

A

Inhibits sodium-potassium ATPase pump, competition with potassium for binding sites

Plants:

  • Lily of the valley
  • Oleander
  • foxglove
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10
Q

Cardiac glycosides

Clinical signs

A

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)
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11
Q

Cardiac glycosides

Diagnosis

A

Based on history

Access to plants

Clicial signs

Analysis of vomit

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12
Q

Cardiac glycosides

TX

A

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
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13
Q

Cyanide toxicity

about

MOA

A

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

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14
Q

Cyanide tox

Clinical signs

A

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

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15
Q

Cyanide tox

DX

A

Cherry red unclotted blood

Analysis of frozen stomach contents

  • prevents cyanide from volatalizing
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16
Q

Cyanide tox

TX

A

Two steps

  1. Induce methemoglobin
    * sodium nitrite binds to cyanide
  2. 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

17
Q

Methylxanthines

A

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

18
Q

Methylxanthines

MOA

A

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
19
Q

Methylxantines

Clinical signs

A

Vomiting, diarrhea, diuresis

Hyperativity

Panting

Tachycardia, hypertension

Ataxia

Tremors, seizures

Coma

Death from arrhythmias or resp failure

20
Q

Gossypol

A
  • 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
21
Q

Gossypol

MOA

A
  • 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
22
Q

Gossypol Toxicity

Clinical signs

A
  • 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
23
Q

Gossypol

Diagnosis

A
  • diagnose by history of ingestion of cottonseed
  • cardiac decrosis, edema, vacuolization
  • chemicaly analysis of gossypol
  • ddx
    • pale muscles also ionophores
24
Q

Gossypol

TX

A
  • remove cottonseed
  • feed high protein diet
  • vitamin a
  • iron and lysine
    • gossypol binds to lysine
  • symptomatic treatment
25
Q

Cantharidin:

Blister beetle or spanish fly

A
  • SE USA, not many beetles required
  • Usually affects horses
    • 6-250 beetles can be lethal
  • associated with grasshopper populations
    • eggs develop on grasshopper larvae
  • Beetles found on alfafa, especially flowering
    • crimped alfalfa common culprit
  • May congrete in isolated spots of hay
    • hard to detect in large amount of hay
26
Q

Cantharidin

MOA

A
  • Inhibits protein phosphatases
  • mucosal irritant
  • causes cardiotoxicity
27
Q

Cantharadin

Clinical Signs

A
  • Colic
  • frequent urination,
  • diaphragn contraction with heart beat
  • shock
  • severe ulceration/irritation
    • oral, GI, bladder epithelium
  • causes cardiotoxicity
28
Q

Cantharadin

Diagnosis

A
  • alfalfa hay consumption
  • beetles in hay/stomach
  • hypocalcemia, inc BUN
  • ulceration of mucous membranes
  • cardiac necrosis
    • may lead to hypovolemia
29
Q

Cantharidin

TX

A
  • GI decontamination
  • GI protection
    • sucralfate
  • antibiotics
30
Q

Case study

  • HX
    • Barky, 2year old spayed female mixed breed dog, lives on farm that grows corn and wheat, uses organophosphates. Patient showing signs of lethargy and anorexia past few days, now dyspnic
  • PE
    • HR: 170bpm (70-120)
    • RR: 90bpm (18-34)
    • Gait, hydration normal, Barky very depressed
    • Abdomimal palp and neuro exam WNL
  • Lab values
    • WBC 7,000 (6,000-17,000)
    • RBC 3.3 X 106 (5.6-8.7 X 106)
    • Platelets 438 (145-440)
    • Glucose 168 (55-102)
    • Protein 4.7 (5-7)
A

Warfarin, was bleeding

Do clotting tests

Vitamin K TX

Toxicology (10 decks)

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