Blood Drugs Flashcards
what are the goals of normal hemostasis
1) prevent prolonged hemorrhage
2) prevent spontaneous thrombosis
what are the 4 stages of hemostasis
1) vasospasm (vasoconstriction)
2) platelet response
3) coagulation
4) fibrinolysis (clot dissolution)
what are some prothrombogenic factors
- vasoconstriction
- platelet activators
- procoagulants
- fibrinolytic inhibitors
what are some antithrombogenic factors
- vasodilators
- platelet inhibitors
- anticoagulants
- fibrinolytic activators
what happens during vasospasm (stage 1 of hemostasis)
- immediate vasoconstriction mediated by myogenic properties of the vessel wall (recoil)
- release of sympathetics and local factors such as thromboxane
what happens during the platelet response
platelets adhere to exposed collagen in the damaged endothelium and to each other; the platelet plug then releases factors to recruit more platelets, promote vasoconstriction and initiate coagulation (TXA2, 5-HT and ADP)
what happens during the coagulation phase (phase 3) of hemostasis
sequential conversion of inactive proteins into active proteases, resulting in conversion of soluble fibrinogen to insoluble fibrin and formation of a net -> clot proper
what is the main initiator of coagulation
tissue factor -> factor VIIa
what happens during fibrinolysis
dissolution of the clot proper (thrombus) by proteolytic actions of plasmin
occurs once wound has healed to restore blood flow
what can cause excessive bleeding
- platelet deficiency (thrombocytopenia, VWD)
- clotting factor deficiency (single factor such as hemophilia or multiple factors such as vitamin K deficiency)
- fibrinolytic hyperactivity
hemophilia can involve what clotting factors
VIII and IX
what are the 2 forms of vitamin K and which is used pharmacologically
Vitamin K1: phytonadione (food)
Vitamin K2: menaquinone (intestinal bacteria)
what is the MoA of vitamin K1
post-translationally modifies coagulation factors II, VII, IX, X
how is vitamin K1 absorbed
fat soluble -> uses bile salts for intestinal absorption
what are the routes for vitamin K1 administration and which is recommended?
IV, IM, SQ
SQ recommended as safest. IM causes hematoma formation and IV associated with anaphylaxis
what are the uses of vitamin K1
1) vitamin K1 deficiency (rodenticide toxicity, sweet clover poisnoning aka dicumoral toxicity)
2) warfarin overdose
what is the MoA of desmopressin acetate (DDAVP)
transiently increases Von Willebrand activity
what are the uses of desmopressin acetate (DDAVP)
- treatment of mild von Willebrand disease
- transiently reduces capillary bleeding during surgery (prophylactic)
what are the routes of administration of desmopressin acetate
nasal and injectable
what is the caveat for using desmopressin acetate during surgery
lasts 2hrs, repeated doses have a reduced effect
what is the MoA of protamine sulphate
binds to and neutralizes heparin; better against high molecular (unfractioned) heparin
what are the uses of protamine sulphate
heparin overdose
how is protamine sulphate given
IV slowly; accurate dose needed
why are accurate doses of protamine sulphate needed
too much causes anticoagulant effects
plasmin lyses fibrin and fibrinogen by attaching to fibrin on __________
lysine binding sites
what is the MoA of aminocaproic acid (Amicar)
binds to the lysine binding site on fibrin and competitively inhibits plasmin
what are the uses of aminocaproic acid
to stop bleeding from fibrinolysis; as an adjunct therapy for hemophiliacs
a red thrombus is _______ rich and contains a large number of ______, it is _________ in origin
a white thrombus is _______ rich and contains a large number of _________; it is __________ in origin
fibrin; RBCs; venous
platelet; platelets; arterial
pathogenesis of thrombosis requires (3)
- local vessel injury
- changes in blood flow (stasis or turbulence)
- altered blood coagulability
what are the 3 drug classes of anticoagulants
1) systemic anticoagulants
2) antithrombotic drugs
3) fibrinolytic drugs
what is the MoA of heparin
binds to ATIII and forms a heparin-ATIII complex that inhibits activated Xa and IIa
what is the composition of heparin
mix of sulphated mucopolysaccharides isolated from mast cells
what are the uses of heparin
as an acute anticoagulant to initially treat thrombosis and thromboembolic disease
what is the caveat of heparin
only prevents new clot formation
what are some adverse effects of heparin and how can we mitigate this
- bleeding
- monitor aPTT
- can give protamine sulphate if overdose
what is Enoxaparin (Lovenox)
low molecular weight heparin
what are the advantages of Enoxaparin over regular unfractioned heparin
- less bleeding tendency
- less risk of thrombocytopenia
- improved pharmacokinetics: can give SQ, increased half life
how does Enoxaparin differ from heparin
Enoxaparin only inhibits Xa but not thrombin (IIa) making it less “effective” but safer
what is a disadvantage of Enoxaparin over heparin
protamine sulphate is not as effective at reversing an overdose of Enoxaparin vs heparin
what is the MoA of warfarin
inhibits Vitamin K factors II, VII, IX, X and stops clotting after existing factors are used
what are the uses of warfarin
in the past has been given as a chronic preventative anticoagulant and is commonly given as a first dose with heparin (works later)
what are adverse effects of warfarin
1) bleeding (combat with Vitamin K1)
2) crosses the placenta so cannot give to pregnant animals
how do we monitor warfarin therapy
international normalized ratio (INR) which is the patients PT/mean normal PT for the lab
want to see 2.0-3.0
what is the MoA of rivaroxaban
selective Xa inhibitor
how does rivaroxaban differ from enoxaparin
rivaroxaban does not interact with ATIII, unlike enoxaparin
rivaroxaban can be given orally
what is a main advantage of rivaroxaban
no monitoring required with a fixed dosage unlike with using heparins or warfarin
what is the main use of rivaroxaban at the moment
dogs with IMHA
what is the MoA of aspirin
inhibits COX-1 selectively (at low doses), preventing TXA2 production in platelets and therefore reducing platelet aggregation
what are the uses of aspirin
prevents thrombus formation and re-thrombus formation
what are some side-effects of aspirin
- bleeding
- gastric ulceration
- renal damage
what is the MoA of clopidogrel
Irreversibly inhibits the binding of ADP to its receptors (P2Y12 or P2YADP), resulting in impaired platelet aggregation
what is a consideration regarding the pharmacokinetics of clopidogrel
it is a prodrug and must be activated by P450 metabolism in the liver
what are the main uses of clopidogrel
for thromboembolic concerns in dogs with IMHA and cats with HCM
what is the MoA of t-PA
binds fibrin and preferentially activates clot-bound plasminogen
what are the uses of t-PA
thromboembolic therapy for canine pulmonary thromboembolism and feline saddle thrombus
given as a CRI due to short half-life
what are adverse effects of t-PA
bleeding tendencies and reperfusion injury
what is the MoA of erythropoietin
stimulates proliferation-differentiation of RBC precursors and release of reticulocytes
what are the uses of EPO
- anemia of CKD
- anemia of cancer
if you give EPO you should expect to see therapeutic results in
2-4 weeks
what are adverse effects of EPO
hypertension, seizures, therapeutic failure
