L4. Long Acting Anticoagulants Flashcards
Pesticides
Rodenticides
Insecticides
Molluscicides
Avicides
Herbicides
Fungicides
Algaecide
Rodenticide Risk:
Rats, mice, gophers, moles
Dangerous becuase they are designed to be both attractive to and lethal to mammals
Rodenticide Types
Anticoagulants
bromethalin
cholecalciferol
Strychnine
Zinc phosphide
Anticoagulants
Previously the most commonly used
Primarily affects dogs and wildlife
Other species occasionally affected
EPA made a large change in the last few years
Anticoagulants:
First Generation
- Warfarin:
- identified as Wisconsin Animal Research Farm
- Form dicoumarol found in hemorrhagic disease of cattle
- Grazing moldy sweet clover
- Diphacinone
- tomcat
- ramik
- Mousemaze
- Chorophacinone
- rozol
Anticoagulants:
Second Generation
- Efficacious agianst warfarin resistant rats
- Typical concentration is 0.005%
- Brodifacoum
- talon, havoc, bolt, volid, D-con mouse pruf2
- Diphethialone
- D-cease, hombre, generation
Anticoagulants:
Second Gen
Tox
More potent
longer acting
Potential for relay toxicosis
Toxicokinetics
Oral absorption levels peak in minutes to hours
Plasma Half life:
warfarin - 14 hrs
Diphacinone - 4.5 days
Brodifacoum - 6 days
Normal Clottng Mechanism
Anticoagulant:
Mechanism of Action
Vitamin K1 is regenerated by Vitamin K1 epoxide reductase
Anticoagulants block this recycling
Also interfere with utilization by blocking synthesis of Vit. k dependent clotting factors
Factor Vll (PT) affected early
Factor lX (ptt) later on
Interference with vitamin K
Anticoagulants
Toxicity
- Acute oral LD50 in dog
- Warfarin 20-300
- Brodifacoum
- Bromadiolone
- Diphacinone
Start Therapy if dosage estimate is ¼ of LD10
Anticoagulant
Risk Factors
- geriatric or neonatal animals
- Concurrent liver diaseas
- Ruminats, horses – moldy sweet clover
- Protein displacing drugs
- phenylbutazone
- Also Corticosteroids, Aspirin
- Impaired platelet function or low counts
Anticoagulants
Kinetics
- 1st generation has ½ lives of several hours
- effects last a few day
- 2nd gen has ½ lives of several days
- effects last 12-30 days
- Drugs that suppress liver metabolism inreases duration
- cimetidine, sulfonamides, fluconazole, phenylbutazone
Anticoagulants:
Delayed Effects
Depletion time for active Vitamin K
Half life of K dependent clotting factors
Clinical coagulopathy usually form 6 days post ingestion
As short as 36hr
PT drops first, ptt later
Anticoagulants:
Clinical Effect
Related to hemorrhage and blood loss
Often weak, anemic, dyspnea, epistaxis,
Melena, lameness, ataxia
Occasional CNS signs
Hemothorax
May be acute death with no early signs
Anticoagulants,:
Necropsy Lesions
Hemorrhage, hematomas, hemothorax
Hemarthrosis, subdural hematomas
Occus in a variety of tissues, organs, spaces
platelet function normal
Anticoagulants:
Clinical Picture
Clinical signs delayed
Initial signs are non-specific
Lethargy, depression, pallor
Varied Sx of bleeding tendency
Anemia
Melena, bloody vomit/diarrhea, point/area bleeding on mucous membranse, epistaxis, hematomas
Bleeding into joints/sc bleeding in feet can cause lameness
persistent bleeding form venipuncture sites
Anticoagulant:
Diagnosis
Presence of hemorrhagic syndrome
Clotting time prolonged
Prothrombin time post exposure
Activated partial thromboplasitn time
PIVKA – proteins induced by Vit K antagonists (Thrombotest)
Detects precursor proteins of clotting factors
Diagnostics
Detection of acitve ingredient in liver, blood, bait
Liver: sample of choice in deceased animals
Blood: Sample of Choice in live animals
Hay: for dicoumarol
Clinical Patholgy
Regenrative / non-regenerative normocytic, normochromic anemia
Often leukocytosis
+/- thrombocytopenia
Abnormal clotting profile
One-stage prothrobim time
Activated parital thromboplasitn time
Thromin time
Activated clotting time
Differential DIagnosis
Dicoumarol - livestock via moldy hay
Idiopathic coagulopathy
Autoimmune thrombocytopenai
DIC
Hereditary
Liver disease
Treatment
Supportive
Releive hemothroax, raise PCV, Rx shock
Vitamin K1 (Vit K3 ineffective)
Oral route with fatty food prefered
Time lag 3-6+ hours for effetive coagulation
Vit K1 has a high incidence of anaphylaxis when given IV
When phytonadione is used orally with a high fat meal rapid absorption and acitvation of phytonadione is nearly equal to IV administration