Cardiovascular and Hematopoietic Toxicity Flashcards
(37 cards)
1
Q
Anticoagulants and anticoagulant rodenticide
A
Widely used by homeowners and professionals for rodent control
1st and 2nd generation compounds
2
Q
1st generation rodenticide compounds
A
- ex: warfarin
- Short half life (15 hours)
- Low potency, required multiple feedings (LD50 = 10-50 mg/kg)
3
Q
2nd generation rodenticide compounds
A
- ex: brodifacoum
- Long half life (20 days)
- High potency, kills in single feeding (LD50 = 0.25 mg/kg)
4
Q
MOA of anticoagulants/rodenticides
A
- Inhibits vitamin K1 epoxide reductase
- Prevents formation of Vit K dependent clotting factors (2, 7, 9, 10)
5
Q
Clinical signs of anticoagulant/rodenticides
A
- 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
Q
Diagnosis of anticoagulant/rodenticides
A
- *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
Q
Treatment of anticoagulant/rodenticides
A
- 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
Q
nitrate toxicosis
A
- Found in fertilizers, many plants, contamination of water
- susceptibility: pigs>cattle>sheep>horses
9
Q
MOA of nitrate toxicosis
A
- 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
Q
clinical signs of toxicosis
A
- 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
Q
diagnosis of nitrate toxicosis
A
- Diagnosis by nitrate levels in feed or water
- In suspected nitrate death, save eye for analysis of nitrate
12
Q
treatment of nitrate toxicosis
A
-
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
Q
cardiac glycosides
A
- contain glycosides
- mostly ornamental plants
14
Q
MOA of cardiac glycosides
A
Inhibit the Na/K ATPase pump through competition with K for binding sites
15
Q
Clinical signs of cardiac glycosides
A
- 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
Q
diagnosis of cardiac glycosides
A
Based on history, access to plants, and clinical signs as well as analysis of vomit
17
Q
treatment of cardiac glycosides
A
- 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
Q
cyanide toxicity
A
- 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
Q
MOA of cyanide
A
- Inhibition of cytochrome C oxidase
- Blocks mitochondrial function and cellular respiration
20
Q
clinical signs of cyanide
A
- 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
Q
diagnosis of cyanide
A
- History of ingestion and unclotted red blood
- analysis of frozen stomach contents
22
Q
treatment of cyanide
A
- induce methemoglobin formation with sodium nitrite to bind cyanide (cyanide likes ferric iron and preferentially binds to it)
- Give sodium thiosulfate to increase formation of thiocyanate by rhodanese. Thiocyanate is non-toxic and eliminated
- If necessary, treat metHb with methylene blue
23
Q
Methylxanthines
A
- 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
Q
MOA of methylxanthines
A
-
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**
