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Pharm Chapter22
Pharmacology of Hemostasis and Thrombosis
| Question | Answer |
|---|---|
| Aspirin MOA | Inhibit platelet cyclooxygenase, blocking TxA2 generation and inhibiting plaelet granule release rxn and platelet aggregation; Inhibits COX-1 and COX-2 nonselectively |
| Clinical applications aspirin | Prophylaxis against TIA, MI, and thromboembolic disorders, Treatment of acute coronary syndromes |
| Adverse effects aspirin | GI bleeding, Reye's syndrome |
| Dipyramidole MOA | Inhibit platelet cAMP degradation and thereby decrease platelet aggregability (Phosphodiesterase inhibitor); vasodilatory properties, may induce angina bt causing the coronary steal phenomenon |
| Clinical applications dipyridamole | Prophylaxis against thromboembolic disorders |
| Dipyridamole usually administered with? | Aspirin, or warfarin |
| ADP Receptor Pathway Inhibitors | Ticlodipine, Clopidogrel |
| Clinical applications ticlodipine | Secondary prevention of thrombotic strokes in patients intolerant of aspirin, Prevention of stent thrombosis(in combination with aspirin) |
| Adverse effects ticlodipine | neutropenia, TTP, myelotoxicity |
| Clinical applications clopidogrel | Secondary prevention of atherosclerotic events in patents with recent MI, stroke or peripheral vascular disease, Acute coronary syndromes, Prevention of stent thrombosis(in combination with aspirin) |
| Adverse effects of clopidogrel | GI hemorrhage(in combination with aspirin), HF |
| GPIIb-IIIa antagonists | Eptifibatide (reversible), abciximab (irreversible), tirofiban (irreversible) |
| Clinical applications eptifibatide | Acute coronary syndroms, percutaneous coronary intervention |
| Adverse effects eptifibatide, abciximab, tirofiban | major bleeding, intracerebral hemorrhage |
| Clinical applications abciximab | adjunct to percutaneous coronary intervention or atherectomy to prevent acute cardiac ischemic complications, unstable angina |
| Clinical applications tirofiban | acute coronary syndromes in patent undergoing angioplasty or atherectomy of managed medically |
| Warfarin MOA | Inhibit hepatic epoxide reductase that catalyzes the regeneration of reduced vitamin K, which is required for synthesis of biologically active coagulation factos II, VII, IX, X and anticoagulant proteins C and S |
| Clinical applications warfarin | Prophylaxis and treatment of PE, DVT, systemic embolism |
| Adverse effects warfarin | Skin and other tissue necrosis(promptly give FPP), hemorrhage |
| Contraindications warfarin | pregnancy, hemorrhagic tendency or blood dyscrasia, bleeding tendency associated with active ulceration, etc. |
| What needs to be monitored with warfarin usage? | PT |
| What decreases the effect of warfarin? | cholestyramine; carbamazepine, barbiturates, benzodiazapenes, rifampin; vitamin K |
| What increases the effect of warfarin? | chloralhydrate; amiodarone; clopidogrel, ethanol, fluconazole, fluoxetine, metronidazole, sulfamethoxazole; broad spectrum antibiotics; anabolic steroids (testosterone) |
| MOA unfractionated heparin | combines with antithrombin III and inhibits secondary hemostasis via nonselective inactivation of thrombin(factor IIa), factor Xa, factor IXa, factor XIa, and factor XIIa |
| MOA LMW heparin | combine with antithrombin III and inhibit secondary hemostasis via relatively (3-fold) selective inactivation of factor Xa |
| Clinical applications unfractionated heparin | prevention and treatment of PE, DVT, cerebral thrombosis, or left ventricular thrombus; prevention of systemic embolism associated with MI; unstable angina |
| Adverse effects unfractionated heparin | hemorrhage, HIT, intracerebral hemorrhage |
| Contraindications unfractionated heparin | HIT, active major bleeding, bleeding tendencies, suspected intracranial hemorrhage |
| LMW heparins | enoxaparin, dalteparin, tinzaparin |
| Clinical applications enoxaparin, dalteparin, tinzaparin | Prevention and treatment of DVT, Treatment of acute coronary syndromes and adjunct to percutaneous coronary intervention (enoxaparin and dalteparin) |
| Adverse effects enoxaparin, dalteparin, tinzaparin | Hemorrhage, thrombocytopenia |
| Contraindications enoxaparin, dalteparin, tinzaparin | active major bleeding, HIT, Renal insufficiency |
| MOA fondaparinux | combine with antithrombin III and inhibits secondary hemostasis via highly selective inactivation of factor Xa |
| Clinical applications fondaparinux | prophylaxis and treatment of DVT and PE |
| Adverse effects fondaparinux | hemorrhage, thrombocytopenia |
| Contraindications fondaparinux | Active major bleeding, severe renal impairment |
| Direct Thrombin Inhibitors | Hirudin related agents - lepirudin, desirudin, bivalirudin; argatroban |
| Clinical applications lepirudin | HIT (inhibits both free and fibrin-bound thrombin) |
| Clinical applications desirudin | prophylaxis against DVT |
| Clinical application bivalirudin | anticoagulation in patients undergoing coronary angiography and angioplasty |
| Adverse effects lepirudin, desirudin, bivalirudin | HF, bleeding |
| Contraindications lepirudin, desirudin, bivalirudin | Active major bleeding |
| Clinical applications argatroban | HIT (dose adjustment is required in patients with liver disease because argatroban is excreted in the bile) |
| MOA r-APC | proteolytically inactivates factors Va and VIIIa; may also exert anti-inflammatory effect by inhibiting TNF production and blocking leukocyte adhesion to selectins |
| Clinical applications r-APC | severe sepsis with organ dysfunction and high risk of death |
| Adverse effects r-APC | hemorrhage |
| Contraindications r-APC | recent intracranial or intraspinal surgery or severe head trauma within 2 months, kidney failure, chronic liver failure, thrombocytopenia |
| Thrombolytic agents | Streptokinase, t-PA (alteplase), tenecteplase, reteplase |
| MOA streptokinase, t-PA (alteplase), tenecteplase, reteplase | proteolytically activate plasminogen to form plasmin, which digests fibrin to fibrin degradation products |
| Clinical applications streptokinase | ST elevation MI, PE |
| Adverse effects streptokinase | anaphylactoid reaction |
| Contraindications streptokinase, t-PA (alteplase), tenecteplase, reteplase | Cerebrovascular accident within 2 months; hemorrhagic stroke (t-PA) |
| Clinical applications t-PA (alteplase) | Acute MI, PE (causes fibrinolysis at the site for a fresh thrombus) |
| Adverse effects t-PA (alteplase) | GI hemorrhage, intracranial hemorrhage |
| Clinical applications tenecteplase, reteplase | Acute MI (longer half life than t-PA, tenecteplase - single bolus, reteplase - double bolus) |
| MOA protamine | Inactivates heparin by forming a stable 1:1 protamine:heparin complex |
| Clinical application protamine | heparin overdose (cannot reverse the anticoagulant effect of fondaparinux) |
| MOA aprotinin | inhibits serine proteases, including plasmin, t-PA, and thrombin |
| Clinical applications aprotinin | reduce perioperative bleeding during coronary artery bypass graft surgery (may inhibit kallikrein, thus paradoxically inhibit the coagulation cascade) |
| Adverse effects aprontin | may increase the risk of postoperative acute renal failure |
| MOA aminocaproic acid, tranexamic acid | Analogues of lysine that bind to and inhibit plasminogen and plasmin |
| Clinical applications aminocaproic acid, tranexamic acid | disorder involving the fibrinolytic system, hemorrhage from increased fibrinolysis |
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