Lecture 19 - Blood Toxicants Tutorial Flashcards
- Anticoagulant rodenticides come in what formulations?
- What color are these formulations?
- Pellets, grains, powders, bait bars, liquids
- Green, red, orange, yellow, etc
Not all rodenticides are?
anticoagulants
Examples: – Bromethalin, cholecalciferol, strychnine, zinc
phosphine, others
After anticoagulant rodenticide is ingested, it is absorbed, leading to __________ of vitamin K1 epoxide reductase. This leads to the __________ of the synthesis of Vitamin K-dependent clotting factors, which leads to the depletion of existing clotting factors. The patient will typically start to bleed ___-___ days post-exposure.
After anticoagulant rodenticide is ingested, it is absorbed, leading to inhibition of vitamin K1 epoxide reductase. This leads to the inhibition of the synthesis of Vitamin K-dependent clotting factors, which leads to the depletion of existing clotting factors. The patient will typically start to bleed 3-5 days post-exposure.
- Name the enzyme that converts inactive coagulation proteins to active coagulation proteins.
- Name the enzyme that converts inactive vitamin K into active vitamin K.
- Vitamin K-dependent carboxylase
- Vitamin K epoxide reductase & Vitamin K reductase.
ACRs inhibit the enzyme ___________ ___ _______ _________ and hence impair the recycling of Vitamin K.
ACRs inhibit Vitamin K epoxide reductase and hence impair the recycling of Vitamin K.
When this enzyme is inhibited, the oxidized Vitamin K epoxide can not be converted to _________, _________ form of Vitamin K. As a result, Vitamin K dependent clotting factors can not be _________.
ACRs only inhibit the synthesis of _____ clotting factors and do not effect ______ clotting factors already in circulation. This is why you only see clinical signs 3-5 days post-ingestion, because that is when pre-formed factors are depleted.
When this enzyme is inhibited, the oxidized Vitamin K epoxide can not be converted to reduced functional form of Vitamin K. As a result, Vitamin K dep, clotting factors can not be activated.
ACRs only inhibit the synthesis of new clotting factors and do not effect preformed clotting factors already in circulation. This is why you only see clinical signs 3-5 days post-ingestion, because that is when pre-formed factors are depleted.
What are the Types of anticoagulant rodenticides?
What are the Half-lives of common anticoagulant
rodenticides
Warfarin
Diphacinone
Brodifacoum
Bromadiolone
Important: it takes ~ ____ half-lives for the toxicant to be cleared from the body – this means ____ days or _____ for ____-acting ACRs
Important: it takes ~ 5 half-lives for the toxicant to be cleared from the body – this means 30 days or more for long-acting ACRs
LD50 tells us nothing about ____________ toxic dose (MTD). NO good information about ____ and _____ exists for ACRs.
LD50 tells us nothing about minimum toxic dose (MTD). NO good information about MTD and MLD exists for ACRs
In the absence of literature on MTD and MLD, some use a value based on “_____ __ ______”
– Assumes minimum lethal dose (MLD) is ___/10 of the LD50, and minimum toxic dose is ___/10 of the MLD
* Very unscientific, often ________ assumptions
In the absence of literature on MTD and MLD, some use a value based on “Rule of Tens”
– Assumes minimum lethal dose (MLD) is 1/10 of the LD50, and minimum toxic dose is 1/10 of the MLD
* Very unscientific, often INCORRECT assumptions
- DO NOT USE THE “RULE OF TENS”
– Death often determined by where _______ occurs - Animals have died after ingesting much _____ than 1/10 of the LD50
- Not much difference between ______ and _____ for ACRs
- DO NOT USE THE “RULE OF TENS”
– Death often determined by where bleeding occurs - Animals have died after ingesting much less than 1/10
of the LD50 - Not much difference between MTD and MLD for ACRs
What are the clinical signs?
- Delayed!
– Typically start ___ to ___ days post-ingestion
* Start after depletion of _______ active factors - Signs are associated with _______
– Signs can be _____ or _______
– Bleeding can occur _________ - ______ depend on where the bleeding is
occurring
– ______ or _______
– _______ in body
- Delayed!
– Typically start 3 to 5 days post-ingestion
* Start after depletion of circulating active factors - Signs are associated with bleeding
– Signs can be subtle or blatant
– Bleeding can occur anywhere - Signs depend on where the bleeding is
occurring
– Internal or external
– Location in body
Blood coagulation involves 2 pathways:
1. Intrinsic
2. Extrinsic
Operate independently and converge at common pathway, causing soluble plasma protein, fibrinogen, to be converted into insoluble fibrin polymer which stops the bleeding.
In each pathway, at least one factor depends on Vitamin K.
Extrinsic; pathway: factor 7
Intrinsic: fator 9
Common pathway: 2, 10
When vitamin k is deficient, the coagulation cascade is interrupted and formation of insoluble fibrin polymer does not occur.
Half lives: imp in understanding which of the clotting time is first to be prolonged.
first half life that is exceeded when exposed to aCR is factor 7, so extrinsic pathway is the first to be disrupted. this manifests as prolongation of one stage prothrombin time.
if exposure to ACR continues, factor 9 –> intrinsic pathway compromised. APTT is the second clotting time to be prolonged.
ACT is the last clotting time to be prolonged b/c you need to have 95% depletion of factor 10 and 2, both of which have long half lives.
Diagnostic tests contd.
* CBC
– May see anemia
* Mild to severe; regenerative
* But: don’t always see anemia!
– May see thrombocytopenia: platelets used up
– May see neutrophilia
– May see hypoproteinemia
* Radiography: helps to locate site of internal bleeding
* Ultrasound: helps to locate site of internal bleeding
* Thoracocentesis & abdominocentesis: help to identify
type/cause of effusion
- CBC
– May see _____- Mild to severe; __________
- But: don’t always see _______!
– May see ____________: platelets used up
– May see ________
– May see ______________- ___________: helps to locate site of internal bleeding
- ___________: helps to locate site of internal bleeding
- __________ & __________: help to identify type/cause of effusion
- Coagulation panels
– In-house analysis - 3?
– Local human hospitals
- Be sure to send sample from normal dog as well
- ACT (activated clotting time) test
– Vit K-dependent coagulation factors need to
be very severely _________ to see increase
- ACT (activated clotting time) test
- CBC
– May see anemia
* Mild to severe; regenerative
* But: don’t always see anemia!
– May see thrombocytopenia: platelets used up
– May see neutrophilia
– May see hypoproteinemia - Radiography: helps to locate site of internal bleeding
- Ultrasound: helps to locate site of internal bleeding
- Thoracocentesis & abdominocentesis: help to identify
type/cause of effusion - Coagulation panels
– In-house analysis - APTT, OSPT, ACT
– Local human hospitals
* Be sure to send sample from normal dog as well - ACT (activated clotting time) test
– Vit K-dependent coagulation factors need to
be very severely depleted to see increase
The goal of Tx is to activate __________ __________
Give antidote: _____ ______ ______ ____ to _____ these factors.
The goal of Tx is to activate coagulation factors.
Give antidote: oral active Vit K1 to activate these factors.
What is the treatment plan for the scenario 3 patient?
What are the at home care instructions?
