Hematological Agents Flashcards
Aspirin
Antiplatelet drug
Mechanism: irreversibly inhibits COX-1 (lesser to COX-2)–>reduce thromboxane A2 production–>decrease platelet activation and aggregation
Use: prevent thrombosis in pts with coronary, cerebrovascular, or peripheral artery disease
Adverse effects: bleeding risk (ulcers), bronchospasms
Dipyridamole
Antiplatelet drug
Mechanism: phosphodiesterase inhibitor–>prevents cAMP to AMP–> increased cAMP lowers intracellular Ca2+–> reduce platelet activation and aggregation
Use: aggrenox= dipyridamole with aspirin for recurrence of strokes; vasodilator used in combo with warfarin to inihibit embolism from mechanical heart valves
cilostazol= another platelet phosphodiesterase inhibitor
Clopidogrel (Plavix)
Antiplatelet drug, P2Y12 inhibitor (ADP receptor on platelets)
Mechanism: irreversible P2Y12 receptor inhibitor–>reduce platelet activation
Use: reduce incidence of stroke and MI in pts with coronary or peripheral artery disease
Pharmacokinetics: prodrug metabolized by cytochrome p450 (CYP2C19)–>decreased therapeutic effects in decreased CYP2C19
Prasugrel (Effient)
Antiplatelet drug, P2Y12 inhibitor (ADP receptor on platelets)
Mechanism: irreversible P2Y12 receptor inhibitor–>reduce platelet activation
Use: reduce incidence of stroke and MI in pts with coronary or peripheral artery disease
Pharmacokinetics: prodrug metabolized, alternative to pts with decreased CYP2C19)
Ticagrelor (Brilinta)
Antiplatelet drug, P2Y12 inhibitor (ADP receptor on platelets)
Mechanism: reversible P2Y12 receptor inhibitor–>reduce platelet activation
Use: reduce incidence of stroke and MI in pts with coronary or peripheral artery disease
Pharmacokinetics: NOT prodrug; reversible–> rapid recovery after discontinuation
Adverse effects: possible fatal bleeding
Cangrelor (Kengreal)
Antiplatelet drug, P2Y12 inhibitor (ADP receptor on platelets)
Mechanism: reversible P2Y12 receptor inhibitor–>reduce platelet activation
Use: reduce incidence of stroke and MI in pts with coronary or peripheral artery disease
Pharmacokinetics: NOT prodrug; reversible–> rapid recovery after discontinuation
Abciximab (ReoPro)
Antiplatelet, GPIIb/IIIa receptor antagonist, antigen-binding fragment of monoclonal antibody
Mechanism: binds GPIIb/IIIa–>prevent fibrinogen cross-bridges b/t platelets–>prevent platelet aggregation; also bind GPIIb/IIIa on leukocytes–>antiinflammatory/ antiproliferative
Use: pts undergoing coronary interventions, acute coronary syndromes, used in combo with aspirin and heparin preventing restenosis after angioplasty
Pharmacokinetics: intravenous bolus, half life rapid in free plasma, 24 hrs bound to platelet
Adverse effects: bleeding, thrombocytopenia
Eptifibatide (Integrilin)
Antiplatelet, GPIIb/IIIa receptor antagonist
Mechanism: peptide prevents fibrinogen from binding to GPIIb/IIa
Use: pts undergoing coronary interventions, acute coronary syndromes, used in combo with aspirin and heparin preventing restenosis after angioplasty
Pharmacokinetics: intravenous bolus, half life longer in free plasma, short time bound to platelet
Adverse effects: lower risk of thrombocytopenia
Tirofiban (Aggrastat)
Antiplatelet, GPIIb/IIIa receptor antagonist
Mechanism: nonpeptide prevents fibrinogen from binding to GPIIb/IIa
Use: pts undergoing coronary interventions, acute coronary syndromes, used in combo with aspirin and heparin preventing restenosis after angioplasty
Pharmacokinetics: intravenous bolus, half life longer in free plasma, short time bound to platelet
Adverse effects: lower risk of thrombocytopenia
Vorapaxar (Zontivity)
Antiplatelet, protease activated receptor (PAR) antagonist
Mechanism: inhibit PAR-1–>inhibit thrombin effects on platelets–>decrease platelet activation
Use: reduce thrombotic CV events in pts with peripheral artery disease or previous MI
Pharmacokinetics: oral
Adverse effects: intracranial hemorrhage
Counterindications: pathological bleeding, intracranial bleeding, ischemic attack or stroke
Heparin
Anticoagulant
Mechanism: binds antithrombin–>conformational change in AT–>increase binding and inhibiting of factor Xa;
acts as molecular bridge bringing thrombin closer to AT–>increase AT-induced inhibition of thrombin
Use: venous thrombosis, thrombosis during coronary angioplasty
Pharmacokinetics: administered parenterally, binds plasma proteins (dosing difficult), requires monitoring using activated partial thromboplastin time (aPTT) assay (measures intrinsic pathway and common pathway)
Adverse effects: bleeding= short half life so discontinuing stops mild bleeding, protamine sulfate for severe; osteoporosis with long term; thrombocytopenia (type 1= aggregration of platelets, type 2= antibodies against PF4/heparin complex)
Low molecular weight heparin (LMWH) (Enoxaparin)
Anticoagulant
Mechanism: binds antithrombin–>increases rate of inhibition of factor Xa
Use: venous thrombosis, thrombosis during coronary angioplasty
Pharmacokinetics: subcutaneous injection, less plasma protein binding (easier dosing), coagulation monitoring less necessary, cleared by kidney, factor Xa activity assay used
Adverse effects: bleeding, lower risk of thrombocytopenia
Fondaparinux
Anticoagulant
Mechanism: binds antithrombin–>increase rate of factor Xa inhibition
Use: venous thrombosis, thrombosis during coronary angioplasty
Pharmacokinetics: subcutaneous injection, less plasma protein binding (easier dosing), coagulation monitoring less necessary, cleared by kidney, factor Xa activity assay used
Adverse effects: bleeding, lower risk of thrombocytopenia
Hirudin
Anticoagulant, direct thrombin inhibitors (DTIs)
Mechanism: inactivate thrombin directly without having to interact with antithrombin
Parenteral DTI isolated from leach
Discontinued after heparin development
Lepirudin
Anticoagulant, direct thrombin inhibitors (DTIs)
Mechanism: binds active side in thrombin that cleaves fibrinogen; binds to fibrin binding site of thrombin; inhibits free and thrombin bound to fibrin
Parenterally administered
