Cardiovascular and Hematopoietic Toxicity Flashcards Preview

Toxicology > Cardiovascular and Hematopoietic Toxicity > Flashcards

Flashcards in Cardiovascular and Hematopoietic Toxicity Deck (37):
1

Anticoagulants and anticoagulant rodenticide

Widely used by homeowners and professionals for rodent control
1st and 2nd generation compounds

2

1st generation rodenticide compounds

  • ex: warfarin
  • Short half life (15 hours)
  • Low potency, required multiple feedings (LD50 = 10-50 mg/kg)

3

2nd generation rodenticide compounds

  • ex: brodifacoum
  • Long half life (20 days)
  • High potency, kills in single feeding (LD50 = 0.25 mg/kg)

4

MOA of anticoagulants/rodenticides

  • Inhibits vitamin K1 epoxide reductase
  • Prevents formation of Vit K dependent clotting factors (2, 7, 9, 10)

5

Clinical signs of anticoagulant/rodenticides

  • Delayed onset of clinical signs (3-5 days) as clotting factors present in plasma are consumed
  • Initial signs are often depression, anorexia, and anemia
  • Dyspnea, nosebleeds, bleeding gums, and bloody feces
  • Hemorrhage (most commonly in chest/abdomen) and hematoma
  • In clinical setting, prolonged bleeding from injection sites is usually noted

6

Diagnosis of anticoagulant/rodenticides

1. history of exposure
2. evidence of a coagulopathy
3. response to vitamin K1 therapy

Specific hematological tests:

  • increased PT (first18-48 hours)
  • increased APTT or PTT >25% longer than normal with normal platelet counts

7

Treatment of anticoagulant/rodenticides

  • If ingestion has occurred within the last few hours:
    • emetic, adsorbent and cathartic therapy
  • Vitamin K administration
    • 0.25-2.5 mg/kg for exposure to short-acting rodenticides
    • 2.5-5 mg/kg for long-acting rodenticides
  • Therapy should be continued for 10-14 days for warfarin to 30 days for second generation compounds
  • May need transfusion in severe cases

8

nitrate toxicosis

  • Found in fertilizers, many plants, contamination of water
  • susceptibility: pigs>cattle>sheep>horses

9

MOA of nitrate toxicosis

  • Nitrate converted to nitrite
  • Nitrite anion causes vasodilation and oxidized ferrous iron in hemoglobin to the ferric state forming methemoglobin
  • Results in oxygen starvation of tissues

10

clinical signs of toxicosis

  • Depends on levels of metHb
  • <10% asymptomatic, may see changes in MM color
  • 15% cyanosis, blood and MM appear brown
  • 50% serious toxicity - ataxia, seizures, coma
  • >70% death

11

diagnosis of nitrate toxicosis

  • Diagnosis by nitrate levels in feed or water
  • In suspected nitrate death, save eye for analysis of nitrate

12

treatment of nitrate toxicosis

  • IV methylene blue in a 1-2% aqueous solution at a rate of 1-2 mg/kg body weight
    • most effective in ruminants
    • urine will become dark green
  • Use ascorbic acid in cats and horses
  • Educate farmers and ranchers regarding nitrate accumulation in weeds and forages intended for feeding/grazing
  • Can feed cattle corn to increase rate of nitrate reduction by rumen flora

13

cardiac glycosides

  • contain glycosides
  • mostly ornamental plants

14

MOA of cardiac glycosides

Inhibit the Na/K ATPase pump through competition with K for binding sites

15

Clinical signs of cardiac glycosides

  • Can occur anywhere from 1 hour to weeks after ingestion, depending on plant species
  • trembling, staggering and dyspnea often present in grazing animals
  • increase in Ca and intracellular Na
  • racing HR and rhythm/arrhythmia, weak pulse
  • hyperkalemia (K can double)

16

diagnosis of cardiac glycosides

Based on history, access to plants, and clinical signs as well as analysis of vomit

17

treatment of cardiac glycosides

  • GI decontamination
  • Treat arrhythmias with propranolol
  • treat hyperkalemia if needed (diuretics)
  • Use digoxin immune Fab fragments if propranolol ineffective
  • Antidote for digoxin and similar glycosides
  • Bind directly to glycosides
  • Complete resolution of clinical signs within 4 hours

18

cyanide toxicity

  • Usually a problem with consumption of wilted leaves and seeds of wild cherry, white clover, or fresh Sorghum spp. 
  • Also found in fertilizers, pesticides/rodenticides, fumigants, combustion
  • Non-toxic when dry, as hydrogen cyanide is volatile

19

MOA of cyanide

  • Inhibition of cytochrome C oxidase
  • Blocks mitochondrial function and cellular respiration

20

clinical signs of cyanide

  • Generally occur within 15-20 minutes to a few hours after animal consumes toxic forage
  • Classic symptom is cherry red blood that is slow to clot
  • May smell almonds in stomach contents
  • Sudden death, dyspnea, weakness, tremors

21

diagnosis of cyanide

  • History of ingestion and unclotted red blood
  • analysis of frozen stomach contents

22

treatment of cyanide

1. induce methemoglobin formation with sodium nitrite to bind cyanide (cyanide likes ferric iron and preferentially binds to it)

2. Give sodium thiosulfate to increase formation of thiocyanate by rhodanese. Thiocyanate is non-toxic and eliminated

- If necessary, treat metHb with methylene blue

23

Methylxanthines

  • Includes caffeine, theobromine, theophylline
  • Found in chocolate, coffee, medications
  • Most common around holidays associated with chocolate
  • Unsweetened baking chocolate is especially toxic
    • as little as 0.2 oz/kg may kill a dog
  • Other common problems are caffeine tablets and cocoa bean mulch for horses

24

MOA of methylxanthines

  • Competitive antagonist of adenosine receptors
    • causes CNS stimulation, vasoconstriction, and tachycardia
  • Prevents Ca reuptake leading to increased skeletal and cardiac muscle contractility 
  • Inhibits phosphodiesterase
  • Increases cAMP and GMP contractions

25

clinical signs of methylxanthines

  • Vomiting, diarrhea, diuresis
  • Hyperactivity, "bounce"
  • panting, tachycardia, hypertension, ataxia, tremors
  • seizures, coma
  • death from arrhythmias or respiratory failure

26

diagnosis of methylxanthine overdose

  • Chemical analysis of stomach contents, plasma, serum, urine, or liver
  • Theobromine can be detected in serum for 3-4 days after ingestion (b/c of long half-life)

27

treatment of methylxanthine overdose

  • GI decontamination
    • induction of emesis
    • repeated administration (every 3 hours)
  • Monitor EKG
    • Treat arrhythmias with lidocaine (not in cats)
    • if this fails use metoprolol
  • Treat seizures with diazepam or barbiturates
  • Maintain respiration
  • Fluid diuresis may increase excretion

28

gossypol

  • found in pigment glands of cottonseed, provides insect resistance
  • levels vary with preparation and type of cotton (inactivated with heating)
  • high level of energy (fat), protein, and effective fiber
  • lipophilic
  • plasma gossypol increases with time

29

MOA of gossypol

  • chelates iron and causes anemia, reduces protein availability
  • produces toxicity by inhibition of dehydrogenases leading to decreased energy and protein production
    • oxidative stress
  • non-ruminants are more sensitive
    • ruminants tolerate higher levels than monogastrics, horses are resistant

30

clinical signs of Gossypol toxicity

  • Usually occurs with long term feeding, but can be acute onset
  • At lower concentrations, produces weight loss, weakness, and dyspnea
  • Moderate anemia may be present, edema secondary to heart failure
  • Myocardial necrosis, CHF
  • Dairy cows and lambs may die suddenly with minimal lesions

31

diagnosis of Gossypol toxicity

  • Diagnose by history of cottonseed ingestion
  • Cardiac necrosis, edema, vacuolization
  • Chemical analysis of gossypol

32

treatment of Gossypol toxicity

  • Feed high protein diet
  • Add vitamin A, iron, and lysine
    • remove gossypol from the diet
  • Symptomatic treatment

33

Cantharidin

  • toxin in the Blister Beetle
  • eggs develop on grasshopper larvae, so beetle numbers are tied to grasshopper numbers
  • Beetles found in alfalfa, esp. flowering alfalfa
    • crimped alfalfa typically the source
  • May congregate in large groups, so difficult to inspect hay as large numbers in a single bale
  • usually affects horses (6-250 can be lethal)

34

MOA of Cantharidin

  • Inhibits protein phosphatases
  • mucosal irritant

35

clinical signs of Cantharidin

  • Colic, frequent urination, diaphragm contraction with heart beat, shock
  • Causes severe irritation and ulceration of oral, GI, and bladder epithelia
  • Causes cardiac toxicity

36

diagnosis of Cantharidin

  • Alfalfa hay consumption
  • Beetles in hay or stomach
  • Hypocalcemia, increased BUN
  • Ulceration of MM
  • Cardiac necrosis

37

treatment of Cantharidin

  • GI decontamination and protection (sucralfate)
  • antibiotics