Coagulation drugs Flashcards
drugs used to reduce clotting
platelet aggregation inhibitors; anticoagulants; thrombolytics
drugs used in bleeding disorders
plasminogen activation inhibitors; protamine sulfate; vitamin k; serine protease inhibitors; plasma fractions
platelet aggregation inhibitors
dec synth/chemical signals for platelet aggregation; aspirin/other cox inhibitors; ADP receptor blockers; phosphodiesterase inhibitors; GP IIb/IIIA receptor blockers on platelets
aspirin characteristics
prototype cox inhibitor -> inhibits thromboxane A2 synth
ADP receptor blockers
1st gen - ticlopidine; 2nd gen - clopidogrel; 3rd gen - prasugrel
ticlopidine, clopidogrel, prasugrel pk
prodrugs; slow onset; loading dose may be req’d
ticlopidine, clopidogrel, prasugrel pd
irreversible inhibitor of P2Y12 (ADP receptor on platelet surface)
ticlopidine, clopidogrel, prasugrel uses
pt’s intolerant to aspirin; combo w/aspirin; prevention
phosphodiesterase inhibitors - dipyridamole pd
inhibit phosphodiesterase -> inc cAMP; block adenosine uptake (acts at A2 receptors - activate platelet adenylyl cyclase)
dipyridamole uses
combo w/aspirin/warfarin - preventative (prosthetic heart valves); test coronary reserve; NOT anti-anginal (could provoke acute attack - coronary steal)
phosphodiesterase inhibitors - cilostazol characteristics
newer; promotes vasodilation, inhibition of platelet aggregation; treat intermittent claudication (window shopper disease)
blockers of GP IIb/IIIA receptors characteristics
for acute coronary syndromes
blockers of GP IIb/IIIA receptors
ABCIXIMAB; eptifibatide; tirofiban
ABCIXIMAB characteristics
monoclonal antibody against human GP IIb/IIIa
eptifibatide characteristics
cyclic peptide reversible antagonist of GP IIb/IIIa
tirofiban characteristics
nonpeptide reversible antagonist of GP IIb/IIIa
anticoagulants
unfractioned heparin (UFH) -> lead to low molecular weight heparins (LMWH) -> lead to selective factor Xa inhibitors; direct thrombin inhibitors (DTIs); coumarin anticoagulants
heparin characteristics
injectable; fast anticoag; used acutely to stop thrombi formation
heparin pd
binds to antithrombin III to allow more rapid inhibition of thrombin EXCEPT those already bound to fibrin; inhibits ongoing coag, but can’t dissolve pre-existing thrombi; effect directly dose-dependent
low molecular weight heparin characteristics
heterogeneous compounds from depolymerization of UFH; inhibit factor Xa, less effect on thrombin vs UFH; higher therapeutic index vs UFH -> no monitoring needed -> better
heparin adverse effects
bleeding; HYPERSENSITIVITY rxns; thrombosis from longterm use -> dec ATIII (use low-dose heparin); heparin-induced thrombocytopenia type II
heparin-induced thrombocytopenia (HIT) type II
antibodies recognize complexes of heparin, platelet protein (platelet factor 4) -> platelet aggregation, release of platelet contents -> life-threatening; treat: sub heparin w/direct thrombin inhibitor (DTI) or fondaprarinux
reversal of heparin action
excessive anticoag from heparin - treat by stopping drug; if bleeding -> give protamine sulfate
danaparoid characteristics
low molecular weight heparinoid from pig; similar to LMWH -> inhibit factor X; approved for prophylaxis of deep-vein thrombosis in hip replacement surgery; effective in treat of HIT
selective factor Xa inhibitors - fondaparinux characteristics
synthetic pentasaccharide -> binds to ATIII -> conformational change to bind to factor Xa; negligible ATIII activity; for prevention/treat deep-vein thrombosis; daily subQ injection
direct thrombin inhibitors
direct bind active site of thrombin; lepirudin, desirudin, bivalirudin, argatroban
lepirudin characteristics
recombinant form of hirudin - powerful thrombin inhibitor from leeches; can reach/inactivate fibrin-bound thrombin in thrombi; parenterally; no antidote (blood transfusion only)
desirudin characteristics
another recombinant form of hirudin
bivalirudin characteristics
synthetic derivative of hirudin
argatroban characteristics
small molecule thrombin inhibitor
coumarin anticoagulants
warfarin, dicumarol
warfarin, dicumarol pk
oral unlike heparin
warfarin, dicumarol pd
inhibit vit K epoxide reductase -> production of inactive clotting factors (lack gamma-carboxyglutamyl side chains); overcome anticoag effects with vit K
warfarin monitoring
narrow TI; many drug interactions; with prothrombin time (extrinsic, common pathways); warfarin dec fxn’l factor VII -> inc PT
warfarin, dicumarol adverse effects
hemmorrhage; cutaneous necrosis w/dec protein C; crosses placenta -> hemorrhagic disorder in fetus
warfarin, dicumarol contraindications
pregnancy
thrombolytics (fibrinolytics)
lyse thrombi; streptokinase; urokinase; anistreplase; alteplase, reteplase, tenecteplase
thrombolytics pd
lyse thrombi by catalyzing conversion of plasminogen to plasmin; dec acute MI mortality;
thrombolytics uses
when angioplasty not readily available
drugs used to treat bleeding
plasminogen activation inhibitors; protamine sulfate; vit k; serine protease inhibitors; plasma fractions
plasminogen activation inhibitors
aminocaproic acid; tranexamic acid
protamine sulfate pd
antagonizes heparin (from fish sperm/testes); high arginine (cationic) -> complex w/anionic heparin -> dec anticoag activity
vitamin K characteristics
stop bleeding due to oral anticoags (warfarin)
serine protease inhibitors - aprotinin pd
blocks plasmin; inc death risk (w/drawn)
