Anticoagulation therapy Flashcards
Classes of antithrombotic drugs
- Heparin, oral anticoagulants
- Fibrinolytic agents
- Antiplatelets
Antithrombotic drug needs to balance between ____ and ____
efficacy
toxicity
Heparin is normally in _________
granules of mast cells
Difference in 3 forms of heparin:
Size
Antithrombin binding to Xa (all) or both Xa and THrombin (unfractionated)
Heparin binds to ______ and it’s effect is ______
antithrombin;
INcrease rate by 1000x
Unfractionated heparin is given ______, has ____ pharmacokinetics
IV/SC (immediate/delayed)
Poor - poor bioavailability, short half life
(requires hospital admission)
Unfractionated heparin and pregancy
Drug of choice - does NOT cross placenta
LMWH/Fondaparinux is given ____ and has _____ pharmacokinetics
SC
Better - (bioavail + predictable dose response)
(outpatient treatment)
Heparin is used for
DVT/PE + oral anticoag + FIbrinolytic drugs Unstable angina/A. MI Coronary angioplasty/stent placement Surgery + cardiopulm. bypass Kidney dialysis
Heparin toxicity
Bleeding
HIT (heparin induced thrombocytopenia)
Allergic events
Heparin bleeding toxicity fixed by:
–> reverse with protamine sulfate (positively charged)
HIT is caused by
platelet factor 4/heparin complex (antibody - to platelets)
LMWH Heparin examples
lovenox, enoxaprin, dalteparin, nadroparin
Pentasaccharide heparin examples
Fondaparinux, Arixtra
Warfarin (oral anticoagulant) acts by:
Vit K analogue - blocks vit K reductase
Warfarin Pharmacokinetics
90 min absorbed
36-48 half life
full effect needs to wait 2-3 days
Wafarin used to prevent:
Venous thromboembolism
Systemic embolisms (prosthetic heart valves, atrial fibrillation)
Stroke/recurrent infarction/AMI
Warfarin adverse effects
hemorrhage
Teratogenic
Warfarin and pregancy
DO NOT USE - cross placenta
Reverse warfarin effect:
stop drug, give vit K
Plasma transfused - replace coagulation factors
Warfarin DDI (list a few examples to enhance effect)
platelet function - aspirin
Decrease vit K absorption - antibiotics
Displace warfarin - clofibrate/phenytoin
Reduce metabolism/elimination - cimetidine, amiodorone, phenylbutazone
Warfarin DDI (list a few examples to decrease effect)
increase metabolism - barbituates/ripamin
Decrease warfarin absorption - cholestyramine
What are the “new oral anticoagulants” do?
DIrect thrombin/Factor Xa inhibitors
New oral anticoagulants advantages
rapid onset
no food interaction
no monitoring
New oral anticoagulatns disadvantages
bad with kidney disease short t1/2 more GI bleed High cost No antidote
Examples of new anticoagulants
Dabigatran Etexilate (Pradaxa) Apixaban (Eliquis) Rivaroxaban (Xarelto)
Dabigatran Etexilate (Pradaxa) uses + notes
atrial fibrillation
Less intracranial hemmorhage - increase MI
NOT in pt with prosthetic heart valves
Apixaban (Eliquis) used for
atrial fibrillation
Rivaroxaban (Xarelto) used for + notes
Atrial fib + VTE
DIrectly inhibits Xa
Prevent strokes/emboli better than warfarin
Fibrinolytic agents include
tPA (alteplase)
uPA (abbokinase)
Streptokinase (Streplase)
Differences between tPA and uPA agents
tPA binds to fibrin –> cleaves plasminogen
uPA does NOT bind fibrin - converts plasminogen directly
How does streptokinase work?
non-enzymatic protein - complex w/ plasminogen –> activate/convert
Fibrinolytic agent uses:
AMI + aspirin
Ischemic stroke (w/in 3 hr)
DVT
PE
Fibrinolytic agent side effects
hemorrhage
Systemic lytic state - increase plasmin
Allergic reaction/Ab to streptokinase
Antiplatelet drugs target:
platelet production, ADP receptor (activation/aggregation), block adhesion proteins
ADP receptor antongists examples:
thienopyridines (clopidogrel/ticlopidine/prasugrel) - slow - need metabolism to activate
Ticagrelor - ATP analoge
ADP receptor antagonists bind:
ADP receptor P2Y12
Glycoprotein IIb/IIIa inhibitors include
abciximab - mAb
Eptifibatide - cyclic peptide inhibitor
Tirofiban - small molecule inhib
Glycoprotein IIb/IIIa inhibitors adverse effect/fix
bleeding/thrombocytopenia
Reverse with platelet infusions
