Hemolytic Drugs Flashcards
What is the goal of normal hemostasis?
- prevent prolonged hemorrhage
- prevent spontaneous thrombosis
What are the stages of hemostasis?
- Vasospasm
- Platelet response
- coagulation phase
- clot dissolution (fibrinolysis)
What occurs during vasospasm?
- vasoconstriction
- sympathetics and local factors respond to restrict blood flow to the area
What occurs during platelet response?
- forms an initial plug immediately
- platelets adhere to exposed collagen and damaged endothelium
- platelet plug releases chemical mediators to recruit platelets, promote vasoconstriction and initiate the coagulation cascade
What happen during the coagulation phase?
- conversion of soluble fibrinogen to insoluble fibrin forming a net of organized protein around the platelet plug
- if done correctly this phase results in a clot (thrombus)
What happens during clot dissolution/fibrinolysis?
- wound healing and restoration of blood flow
- dissolution of clot
What are the main causes of excessive bleeding? (3)
- platelet deficiency
- clotting factor deficiency
- fibrinolytic hyperactivity
What are the two natural forms of Vitamin K that exist?
- K1: phytonadione (foods)
- K2: menaquinone (intestinal bacteria)
What is the main mechanism of action of vitamin K?-
- confers biological activity of multiple factors
- SC is the recommended route because anaphylaxis and hematomas are possible
- it is very fat soluble so considered to be safe
When would we use vitamin K?
- vitamin k deficiency (rodenticide toxicity or sweet clover poisoning)
- warfarin overdosing
What is Desmopressin acetate (DDAVP) used for?
- increases Von Willebrand activity (helps platelets stick together)
- used prophylactically to control capillary bleeding during surgery
- injectable or nasal spray
What is Protamine Sulfate used for?
- used to treat heparin overdoses (binds to heparin neutralizing its anticoagulant effect)
- give IV slowly to avoid adverse reactions that include collapse
What do we use fibrinolytic inhibitors for?
- plasmin lyses fibrin and fibrinogen
- a fibrinolytic inhibitor like Aminocaproic acid will block lysine binding sites, inhibiting plasmin
- we would use these drugs for bleeding from fibrinolytic therapy or adjunct therapy-hemophiliacs
What is thromboembolic disease?
- thrombus formation of the “blood clot proper”
- thromboemboli migration of thrombus in the body
What does pathogenesis of thrombosis require?
Prothrombic factors
What are some prothrombic factors?
- local vessel injury
- abnormal blood flow (stasis or turbulence)
- altered blood coagulability
What does an ideal systemic anticoagulant include?
- prevents pathologic thrombosis
- allow normal response to vascular injury and limit bleeding
What is the mechanism of action of heparin?
- Enhances the action of antithrombin III which inhibits activated clotting factors
What do we primarily use heparin for?
- initial treatment of thrombosis and thromboembolic disease
- useful as an acute anticoagulant as it has rapid onset
- prevents NEW thrombus formation only, will not lyse existing thrombus
What are some adverse effects of heparin?
- bleeding tendencies
- 1.8-2.5X the normal mean aPTT
- protamine sulfate can neutralize heparin in overdose
What are some key characteristics of Enoxaparin?
- systemic anticoagulant
- low molecular weight heparin
- used more commonly due to less bleeding tendencies, protamine sulfate is less active against LMW heparins, less risk of thrombocytopenia, improved pharmokinetics = can give sub q and longer half life
What are the key characteristics about Warfarin?
- systemic anticoagulant
- oral anticoagulant - antagonizes vitamin K actions
- injectable and oral formulations available
- monitoring using international normalized ratio
What are the adverse effects of Warfarin?
- bleeding tendencies
- serious bleeding requires fresh blood/plasma
- warfarin crosses placenta therefore do not use in pregnancy (heparin does not cross placenta)
What is the mechanism of action of Rivaroxaban?
- selective factor Xa inhibitor
What are the key characteristics of Rivaroxaban?
- systemic anticoagulant
- inactivate factor Xa directly
- does not interact with ATIII and no thrombin activity
- quick anticoagulant activity
- predictable pharmokinetics
- given orally
- bleeding can occur
What are the key characteristics of aspirin?
- cyclooxygenase inhibitor
- irreversibly binds cyclooxygenase-1
- prevents thrombus and re-thrombosis formation
What are some adverse effects of aspirin?
- GI ulceration
- renal damage
- bleeding tendencies
What are the key characteristics of clopidogrel?
- ADP inhibitors
- reduce platelet aggregation by inhibiting ADP pathways
- “prodrug” which must be activated by liver P450 metabolism
- routinely used for thromboembolic concerns in cats (HCM) and dogs (IMHA)
- fairly safe
What do fibrinolytic drugs do?
Rapidly lyse through thrombi by activating plasmin from clot bound plasminogen
What are the key characteristics of tissue plasminogen activator?
- proteases that bind fibrin
- can preferentially activate clot bound plasminogen
- short-half life = constant rate infusion
What do we use tissue plasminogen activator for?
Thromboembolic therapy for canine pulmonary thromboembolism and feline saddle thrombis
What are the adverse effects of tissue plasminogen activator?
- reperfusion injury
- bleeding tendencies
What are the key characteristics of erythropoietin?
- erythropoietin is made by the kidney in response to hypoxia
- used commonly in anemias when there is chronic renal failure
- iron supplementation advised with usage
- increases hematocrit and hemoglobin in 2-4 weeks
What are the adverse effects of erythropoietin?
- hypertension
- seizure
- therapeutic failure from antibody formation (most common)
