Anti-thrombotic Drugs Flashcards
Anti-platelet Agents
interfere with platalet aggregation and activation/primary hemostasis
Side Effects: bleeding dyspepsia, diarrhea
COX inhibitors
aspirin (ischemic HD, stroke, AF if warfarin contraindicated) side effects gastrointestinal
ADP Receptor inhibitors (Thienopyridines)
Mechanism: irreversibly block P2Y12 receptors preventing platelet activation. Normally ADP binds to both purinoreceptors (P2Y1 and P2Y12) which increases intracellular Ca promoting activation.
Agents: clopidogrel, ticlopidine, prasugrel, ticagrelor
Uses: unstable angina and coronary interventions
Unstable angina, MI, coronary intervention, with ASA (acetyl saliicle acid), stroke, peripheral vascular disease,
Side Effects: bleeding dyspepsia, diarrhea
Glycoprotein IIb/IIIa Receptor Antagonists
Mechanism: most potent, reversibly inhibits platelet aggregation preventing platelet binding to fibrinogen and vWF.
Agents: (monoclonal antibodies) abciximab (Fab fragment of chimetic human mouse) (synthetic peptide antagonists) eptifibatide (synthetic non-petide antagonist) tirofiban
Uses: unstable angina and coronary interventions
patients undergoinf percutaneous coronary interventions and high risk coronary syndromes
Side effects: bleeding, thrombocytopenia esp abciximab
Dipyridamole
Mechanism: unclear
Uses: no proven benefits when given by itself. cmobined with warfarin, aspirin
Anti-coagulant (thrombotic) Drugs
interfere with coagulation cascade/secondary hemostasis
Unfractionated Heparin (IV): hetergenous mixture of GAGs glycosaminoglycans.
Mechanism: ehances antithrombin III activity against thrombin (also factor XIa, Xa, and IXa)
Uses: short term anticoagulation ((1) Unstable angina/NSTEMI, (2) acute MI after fibrinolytic therapy (3) pulmonary embolism or deep venous thrombis) requires continouse monitoring (to maintain therapeautic level), effect can be reversed with protamine sulfate
Side effect: 1) bleeding and 2) Heparin induced thrombocytopenia (HIT) either due to induced platelet aggregation (15% of patients usually asymptomattic and dose-dependent) and less commonly immune mediated (3% of patients not dose dependent). Antibodies recognized Heparin/Platelet Factor 4 complexes. PF4 is released from platalet alpha-granules during activation and physiolgical role is thought to antagonize Heparin-like molecule anti-coagulation effect. Immune complexes activate platelets. Life-threatening bleeding and paradoxically thrombosis. Long term used associated osteroporosis.
Low Molecular Weight Heparins: better/longer half life and bioavailability
agents: enoxaparin, dalterparin, tinzaparin
Direct Thombin Inhibitors: UFH and LMW heparin only inactivate circualting thrombin and that activity is dependent on Antithrombin. Direct thrombin inhibitors act independetly of antithrombin and inactive both circulating and fibrin bound thrombin
Agents: Dabigatran (others are lepirubin, bivali_rudin,_ argatroban)
Uses: strove prevention from non-valvular Atrial fibrillation
Factor IXa Inhibitors
Agents: rivaroxiban (Xarelto) (stroke prevention (non-valvular AF), apixaban (non-valvular AF)
Warfarin (oral agent, long term anti-coagulation!)
Uses: long term anticoagulation, AF, post MI, prosthetic valves, pulmonary embolism, venous thromboembolism (embolism and Afib)
Mechanism: indirecly inhibits gamma-carboxyaltion of factors (II, VII, IX, X, plus others like protein C and S) by antagonzing enzyme and thus factors cannot bind calcium and partcipate in coagulation cascade. Delayed onset of 2-7 days thus give UFH and LMW heparin interim.
Side effects:
Fibrinolytic /Thrombolytic Agents
Uses: Acute MI or other thrombsis (i.e stroke)
Mechanism: endogenous plasminogen activated to plasmin which lyses fibrin clot.
Agents: streptokinase (rarely used in USA), urokinase, TPA (tissue plasminogen activator altepase, tPA), reteplase (rPA), and tenecteplase (TNK-tPA). The last two are derivatives of tPA but with longer half lives
