Rodenticides: Anticoagulants Dr. Boots

Question 1

What are the generations of anticoagulant rodenticides

Answer 1

1st: Warfarin
2nd: Brodifacoum, Bromodialone

Question 2

concerning the properties of anticoagulant rodenticides, which generation is slower onset to CS

Answer 2

1st generation: up to 1 week

generally no sooner than 24-36 h for either generation

Question 3

Toxicity of 1st gen vs 2nd gen

Answer 3

1st, toxic when ingested daily for 1 week

2nd, effective after 1 dose

comparative potency of 2nd gens:

Brodifacoum (0.2-4 mg/kg) > Diphacinone (3-7.5 mg/kg) > Warfarin (20-50 mg/kg)

Question 4

which sp most susceptible?

order of sensitivity

Answer 4

dogs most susceptible

Pigs > dogs and cats > ruminants > horses and chickens

Question 5

Factors enhancing toxicity of anticoagulant rodenticides

Answer 5

Vitamin K deficiency (oral sulfonamide therapy)
Liver disease
Enzyme inhibitors (e.g. cimetidine)
Any other concurrent factors that cause hemorrhage, anemia, hemolysis, etc.
Concurrent use of drugs that displace the anticoagulant from protein binding sites
Phenylbutazone, salicylates, sulfonamides, corticosteroids
Administration of steroids or thyroxine may increase
receptor site affinity

Question 6

Toxicokinetics of Anticoagulant rodenticides

Answer 6

Absorption is complete
Reach peak blood level in 6-12 hours
Largely bound to plasma proteins
Achieve higher concentrations in the liver
Metabolized in the liver by hydroxylation
Half life variable depending on generation
Cross the placenta and excreted in milk in small amounts

Question 7

Plasma half life of anticoagulant rodenticides

Answer 7

2nd gen long half life (e.g. brodifacoum or diphacinone)

1st gen: warfarin = 19h

2n gen: brodifacoum = 6d

Question 8

MoA of anticoagulant rodenticides

Answer 8

inhibit Vit K epoxide reductase

Question 9

CS of anticoag rodent.

Answer 9

• *Onset** of clinical signs 1-5 days
• *hemorrhage**

Animals may die without external evidence of bleeding
Abortion in cattle (placental hemorrhage)

Question 10

Lesions of anticoag. rodent.

Answer 10

hemorrhage should be found somewhere!

2ndary bacterial pneumonia

Chem analysis:

Blood (preferred), serum or plasma of live animal

PM: Liver, GI contents/vomitus, sample of bait

Question 11

What coagulation parameter becomes prolonged first

Answer 11

PIVKA - proteins induced by vitamin K antagonists

for PTT (APTT) to become prolonged need 75% gone

for ACT to become prolonged need 90% gone

Question 12

What are other lab findings with anticoagulant

Dx of anticoag. rodenticide

Answer 12

Anemia

Thrombocytopenia

Hypoproteinemia

evidence of hemorrhage on radiograph

Hx, CS, lesions, bw, response to therapy

with hemorrhage, think rodenticide until proven otherwise!

Question 13

DDx for anticoag rodent.

Answer 13

Spoiled sweet clover (cattle, horses)
Vitamin K deficiency (swine, poultry)
Other toxins that can cause hemorrhage – ricin (castor beans), saponins (coffee weeds), monocrotaline (crotalaria), gossypol (cotton seed), aflatoxins, inorganic arsenic, etc
Non-toxin related causes for hemorrhage (thrombocytopenia, DIC, liver disease, specific factor deficiency)

Question 14

Tx for anticoagulant rodenticides

Answer 14

Vitamin K1 aka phytonadione

Vit K3 not effective, side effects

Oral route, or IM/SC but NOT IV (anaphylaxis)

• bioavailability higher w/fatty meal*
• liver failure may decr response to therapy*

Question 15

Tx considerations for anticoag rodent

Answer 15

• *Exposure – very recent/normal coagulation panel**
• If recent enough for decontamination then there will be no clinical signs*
• *Decontamination** (emesis, activated charcoal)
• Start vitamin K*?
• *Exposure – no clinical signs but prolonged coags**
• *Start vitamin K therapy**
• Consider giving clotting factors* (FFP, cryosupernatant)

Clinical – bleeding but PCV >15-20% and stable
Start vitamin K therapy, monitor closely
Give clotting factors (fresh frozen plasma (FFP))
Consider giving RBCs (fresh whole blood)
Clinical – bleeding, PCV < 15%, unstable
Give clotting factors and RBCs (fresh whole blood or FFP
with packed RBCs)
Start vitamin K, monitor closely, supportive care

Question 16

Tx with Vit K

Answer 16

should see improvement in coagulation parameters with 24 hrs
Duration of treatment will depend on agent ingested
Warfarin 1 week
Brodifacoum 4 weeks
If unknown rodenticide default should be 3-4 weeks
Even if known, patient should be tested when Vit K is
discontinued (check PT 26-48hrs after last dose of
Vitamin K, +/- once more at 96 hrs)

Question 17

Px

Answer 17

**Generally treatable – depending on where hemorrhage has occurred
Higher risk (higher sensitivity) to patients in the short term after treatment**
*Lower toxic dose if repeated exposure within next weeks*