Anticoagulants |
Heparins |
Unfractionated heparin | Complexes with antithrombin III • irreversibly inactivates the coagulation factors thrombin and factor Xa | Venous thrombosis, pulmonary embolism, myocardial infarction, unstable angina, adjuvant to percutaneous coronary intervention (PCI) and thrombolytics | Parenteral administration | Bleeding (monitor with aPTT, protamine is reversal agent) • thrombocytopenia • osteoporosis with chronic use |
LMW heparins (enoxaparin, dalteparin, tinzaparin): more selective anti-factor X activity, more reliable pharmacokinetics with renal elimination, protamine reversal only partially effective, less risk of thrombocytopenia |
Fondaparinux: effects similar to those of LMW heparins |
Direct factor X inhibitors |
Rivaroxaban | Binds to the active site of factor Xa and inhibits its enzymatic action | Venous thrombosis, pulmonary embolism, prevention of stroke in patients with nonvalvular atrial fibrillation | Oral administration • fixed dose, no routine monitoring (factor Xa test) | Bleeding • no specific reversal agent |
Apixaban and edoxaban: similar to rivaroxaban |
Direct thrombin inhibitors |
Buvalirudin, argatroban, and dabigatran | Bind to thrombin’s active site and inhibit its enzymatic action | Anticoagulation in patients with heparin-induced thrombocytopenia (HIT) | Bivalirudin and argatroban: IV administration Dabigatran: oral administration | Both: Bleeding (monitor with aPTT) |
Coumadin anticoagulant |
Warfarin | Inhibits vitamin K epoxide reductase and thereby interferes with production of functional vitamin K-dependent clotting and anticlotting factors | Venous thrombosis, pulmonary embolism, prevention of thromboembolic complications of atrial fibrillation or cardiac valve replacement | Oral administration • delayed onset and offset of anticoagulant activity • many drug interactions | Bleeding (monitor with PT, vitamin K1 is a reversal agent) • thrombosis early in therapy due to protein C deficiency • teratogen |
Thrombolytic drugs |
Alteplase, recombinant human tissue plasminogen activator (t-PA) | Converts plasminogen to plasmin, which degrades the fibrin in thrombi | Coronary artery thrombosis, ischemic stroke, pulmonary embolism | Parenteral administration | Bleeding, especially cerebral hemorrhage |
Reteplase, tenecteplase: similar to alteplase but with a longer half-life |
Streptokinase: bacterial protein that forms a complex with plasminogen that rapidly converts plasminogen to plasmin. Subject to inactivating antibodies and allergic reactions |
Antiplatelet drugs |
COX inhibitor |
Aspirin | Nonselective, irreversible COX inhibitor • reduces platelet production of thromboxane A2, a potent stimulator of platelet aggregation | Prevention and treatment of arterial thrombosis | Dose required for antithrombotic effect is lower than anti-inflammatory dose (see Chapter 36) • duration of activity is longer than pharmacokinetic half-life due to irreversible action | Gastrointestinal toxicity, nephrotoxicity • hypersensitivity reaction due to increased leukotrienes; tinnitus, hyperventilation metabolic acidosis, hyperthermia, coma in overdose |
Glycoprotein IIb/IIIa inhibitor (GP IIb/IIIa) |
Abciximab | Inhibits platelet aggregation by interfering with GPIIb/IIIa binding to fibrinogen and other ligands | Used during PCI to prevent restenosis • acute coronary syndrome | Parenteral administration | Bleeding, thrombocytopenia with prolonged use |
Eptifibatide, tirofiban: Reversible GP IIb/IIIa inhibitors of smaller size than abciximab |
ADP receptor antagonists |
Clopidogrel | Prodrug: active metabolite by CYP2C9 and CYP2C19 irreversibly inhibits platelet ADP receptor | Acute coronary syndrome, prevention of restenosis after PCI, prevention and treatment of arterial thrombosis | Oral administration | Bleeding, gastrointestinal disturbances, hematologic abnormalities |
Ticlopidine: older ADP receptor antagonist with more toxicity, particularly leukopenia and thrombotic thrombocytopenic purpura |
Prasugrel: newer drug, similar to clopidogrel with less variable kinetics, activation primarily by CYP3A4 Ticagrelor: reversible ADP receptor antagonist that does not require activation |
Dipyridamole |
Dipyridamole | Inhibits adenosine uptake and inhibits phosphodiesterase enzymes that degrade cyclic nucleotides (cAMP, cGMP) | Prevention of thromboembolic complications of cardiac valve replacement • combined with aspirin for secondary prevention of ischemic stroke | Oral administration | Headache, palpitations, contraindicated in congestive heart failure |
Cilostazol: similar to dipyridamole |
Drugs used in bleeding disorders |
Reversal agents |
Vitamin K1 (phytonadione) | Increases supply of reduced vitamin K, which is required for synthesis of functional vitamin K-dependent clotting and anticlotting factors | Vitamin K deficiency, reversal of excessive warfarin anticlotting activity | Oral or parenteral administration | Severe infusion reaction when given IV or IM |
Protamine: Cationic form is acidic protein administered parenterally to reverse excessive anticlotting activity of unfractionated heparin |
Clotting factors |
Factor VIII | Key factor in the clotting cascade | Hemophilia A | Parenteral administration | Infusion reaction, hypersensitivity reaction |
Plasma and purified human clotting factors: available to treat other forms of hemophilia |
Desmopressin: vasopressin V2 receptor agonist increases concentrations of von Willebrand factor and factor VIII (see Chapter 37) |
Antiplasmin drugs |
Aminocaproic acid | Competitively inhibits plasminogen activation | Excessive fibrinolysis | Oral or parenteral administration | Thrombosis, hypotension, myopathy, diarrhea |
Tranexamic acid: analog of aminocaproic acid |