Anti-thrombosis Flashcards
Aspirin, Ibuprofen (NSAIDS)
Class: Anti-platelet drugs (prevent arterial thrombosis, MI, Stroke with history TIA), unstable angina, percutaneous coronary intervention re-occlusion
MOA: Cyclooxygenase inhibitors → blocks TXA2 synthesis → inhibits platelet aggregation
Clinical Pearls: irreversible; new platelets must be generated to restore clotting; PO
Dipyridamole
Class: Anti-platelet drugs (prevent arterial thrombosis, MI, Stroke with history TIA), unstable angina, percutaneous coronary intervention re-occlusion
MOA: Cyclic AMP modulators → inhibits phosphodiesterase (PDE degrades AMP) → ↑cAMP → inhibit platelet aggregation
Clinical Pearls: PO
Clopidogrel, Ticlopidine, Prasugrel, Ticagrelor
Class: Anti-platelet drugs (Prevention of arterial thrombosis, MI, Stroke w/ history TIA), Unstable angina, Percutaneous Coronary intervention-re-occlusion
MOA: P2Y (ADP) Receptor Antagonists → Blocks ADP receptor → prevent inhibition of Adenyl cyclase → inhibit platelet aggregation
Clinical Pearls: N/A
Vorapaxar
Class: Anti-platelet drugs (Prevention of arterial thrombosis, MI, Stroke w/ history TIA), Unstable angina, Percutaneous Coronary intervention-re-occlusion
MOA: PAR-1 (Thrombin) receptor antagonist
Clinical Pearls: Secondary prevention of M.I, Reversible antagonist of the thrombin receptor on platelets
Abciximab (monoclonal antibody-irreversible)
Class: Anti-platelet drugs (Prevention of arterial thrombosis, MI, Stroke w/ history TIA), Unstable angina, Percutaneous Coronary intervention-re-occlusion
MOA: Glycoprotein IIb/IIIa receptor antagonists → inhibit binding of fibrinogen to platelets → prevent fibrinogen cross-linking of the platelet plug and platelet aggregation
Clinical Pearls: Administered i.v. - rapid
Indicated for ischemic events (unstable angina, percutaneous coronary intervention-re-occlusion)
Eptifibatide (synthetic peptide antagonist)
Tirofiban (non-peptide tyrosine analogue)
Class: Anti-platelet drugs (Prevention of arterial thrombosis, MI, Stroke w/ history TIA), Unstable angina, Percutaneous Coronary intervention-re-occlusion
MOA: Glycoprotein IIb/IIIa receptor antagonists → inhibit binding of fibrinogen to platelets → prevent fibrinogen cross-linking of the platelet plug and platelet aggregation
Clinical Pearls: Lower access to receptor → infusion of platelets → compete with these drugs (reversible)
Heparin (unfractionated heparin: 5-30 kDa, Low molecular weight heparin: 1-5 kDa)
Class: Anticoagulants (Prevention of venous thrombosis)
MOA: Accelerates the binding of ATIII (anti-thrombin III) → strongly inhibits the proteases, thrombin and factors IXa, Xa, XIa, XIIa → inactivate the coagulation factors, Low molecular weight heparin: inactivation of Xa
Adverse Effects: Plasma levels highly variable (dosing problem) → intensive monitoring required, Can be used in pregnancy, hemorrhage -heparin-induced thrombocytopenia (HIT) -allergy
Clinical Pearls: I.v. or sc administration → fast acting -Pulmonary embolism, Evolving stroke, Massive Deep Vein Thrombosis, Low dose for post-operative venous thrombosis and combination with thrombolytic activity for MI, Low molecular weight heparin: lower risk of developing HIT, Protamine Sulfate: heparin overdose
Dabigatran, Argatroban
Class: Anticoagulants (Prevention of venous thrombosis)
MOA: Direct thrombin inhibitors (DTI) → inhibits thrombin by directly binding to freely circulating and clot-bound thrombin (binds to catalytic (active site) of thrombin)
- do not require antithrombin as a co-factor -more predictable response
- no development of heparin induced thrombocytopenia (HITs)
Clinical Pearls: Idarucizumab is an IV monoclonal antibody reversing agent to Dabigatran (Antidote)
Lepirudin
Class: Anticoagulants (Prevention of venous thrombosis)
MOA: Direct thrombin inhibitors (DTI)
- Recombinant polypeptide derived from medical leech protein, hirudin
- Binds to both catalytic site and substrate orientation site (exosite)
- can inhibit both free and fibrin-bound thrombin in developing clots (do not inhibit factor X)
Fondaparinux
Class: Anticoagulants (Prevention of venous thrombosis)
MOA: Selective Factor Xa inhibitors (contains the five essential carbohydrate residues for binding to ATIII and causing ATIII conformational change and inactivation of Xa)
Clinical Pearls: Deep vein thrombosis, heparin derivatives
Apixaban (Eliquis) and Rivaroxahan
Class: Anticoagulants (Prevention of venous thrombosis)
MOA: Selective factor Xa inhibitors → do not require binding to ATIII for activity → bind factor Xa complexed with calcium on phospholipid surfaces
Clinical Pearls: regular blood monitoring not required, event of bleeding → can be used as antidote → inactive form of factor Xa (continue to promote coagulation)
Apixaban: reducing the risk of stroke & dangerous blood clots (systemic embolism) with atrial fibrillation (↓mortality) patients with no heart valve problem (compared to warfarin, lower incidence of bleeding and stroke)
Warfarin
Class: Anticoagulants (Prevention of venous thrombosis)
MOA: Antagonizes vitamin K → epoxide reductase inhibited by warfarin (preventing the recycling of vitamin K → prevents the synthesis of FII, FVII, FIX and FX)
Adverse Effects: Cannot be used in pregnancy (cause first trimester congenital malformations in fetus), Drug interactions Drug interactions:
- ↑ anticoagulant activity (aspirin, amoxicillin) → oral antibiotics
- ↓ anticoagulant activity (Oral contraceptives) -other drugs that promote bleeding (Dipyridamole, Heparin)
Clinical Pearls: Administered PO → slow onset, Acute MI, Atrial fibrillation, Pulmonary embolism, Heart valve disease and replacement
Streptokinase
Class: Thrombolytics (converts plasminogen to plasmin → plasmin degrades fibrin matrix of clots), most effective when given within 4 hours after onset of symptoms
MOA: Fibrinolysis, Bacterial (Streptococcus) protein, Forms a complex with plasminogen → expose the latter’s active site → Product streptokinase -plasminogen can then cleave other plasminogen molecules to plasmin (Recombinant Tissue Plasminogen Activators)
Adverse Effects: Thrombolytic actions of streptokinase are relatively non-specific → can result in systemic fibrinolysis, can induce antigenic responses
Clinical Pearls: Treatment of MI and life-threatening pulmonary embolism (For emergencies only)
Alteplase, Reteplase, Tenecteplase
Class: rTPAs
MOA: Plasminogen is a naturally circulating precursor to plasmin, which degrades the fibrin matrix of clots. rTPAs catalyze this conversion to rapidly degrade any clots
Clinical Pearls: Reserved for inpatient use due to extremely high risk of bleeds (intracranial hemorrhages), Breaks down all the clots in the body (extremely effective and risky)
Fibrinolysis
● Plasminogen is an inactive circulating beta-globulin
● Tissue plasminogen Activator (t-PA): converts plasminogen to plasmin only at a site of clot
● Plasmin digests fibrinogen, fibrin and clotting factors by hydrolysis of peptide bonds
● Recombinant t-PA, Alteplase
○ Effective at reopening occluded coronary arteries
○ However, can induce unwanted bleeding including cerebral hemorrhage
