Drug Therapy in Thrombosis Flashcards
(37 cards)
Used in prophy and tx of venous thrombosis, to prevent further propagation of clots, and used in a-fib and valvular disease to prevent embolism
Anticoagulants
Immediately acting, short half life, parenteral drug followed by what oral. long half life, slowly acting drug; both for anticoagulation
Heparin. Warfarin
Serious complication of heparin? Of warfarin? Are there antidotes?
HIT. Skin necrosis. Yes
Describe the coagulation cascade please
XII to XI to IX+VIII. TF+ VII and IX+VIII activate Xa+Va, which converts prothrombin to thrombin. Thrombin activates fibrinogen to fibrin. PrS acts on PrC+thrombomodulin to form active PrC which prevents the activation of V to Va and VIII to VIIIa.
Heparin is an indirect [ ] inhibitor. It binds to [ ] which potentiates formation of inactivating [ ]-coagulation factor complexes. What factors does it combine with to inactivate?
Thrombin. Antithrombin, antithrombin. IIa and Xa.
Thx effectiveness of heparin is monitored by measuring the [ ] which should be [ ] times the normal value
PTT; 2-2.5.
A highly basic peptide that binds heparin to treat this adverse side effect
Protamine sulfate. Bleeding
Used to maintain patency in dialysis, bypass surgery and in venous lines; to prevent arterial thrombosis in unstable angina pectoris and MI; and to prevent DVT and PE. It’s also the drug of choice in pregnancy because it does not cross the placenta.
Std (unfractionated) heparin
Long-term use of heparin causes what?
Osteoporosis
Hallmark of LMWH. Name 3 diff preparations. Half-life compared to std.
Inhibit thrombin less effectively than factor Xa. Dalteparin, Enoxaparin (Lovenox, best in preg), Tinzaparin. Longer t1/2.
LMWH monitoring is done using what assay?
Heparin assay (anti-factor Xa assay) rather than PTT.
Fondaparinux binds what? Given when? Antidote?
Binds active site of AT, inhibits Xa. Long half-life. Can be given in HIT. CANNOT be reversed when bleeding occurs.
Warfarin is a [ ], aka oral anticoagulant. It blocks the [ ] carboxylation of what factors, preventing their activity.
Vit-K antagonist. Vit-K-dependent y-carboxylation of II, VII, IX and X (and Protein C&S).
Displacement of [ ]-bound warfarin by other meds increases the free conc and its anticoag activity.
Albumin
Long-term antibiotic therapy has what affect on warfarin’s anticoagulant activity? Warfarin metabolism is enhanced by what?
Decreases vitamin K and thus increases anticoagulation. Drug-induced increases in hepatic P450 activity (e.g barbiturates)
Measure warfarin effectiveness with what?
PT/INR
At the onset of thx, because protein C has a short half-life and warfarin inhibits the carboxylation of protein C, a rapid drug-induced decrease in PrC activity may do what?
Balance tipped to pro-coagulation resulting in vascular thrombosis and skin necrosis
Warfarin therapy may be reversed, in ascending order of rapidity, by what?
Stopping the drug, administering Vit K, Prothrombin cpx concentrate (Kcentra: II, VII, IX, X, PrC&S), fresh frozen plasma.
Bivalirudin: class, mechanism, speed, monitoring, antidote, uses
Direct-thrombin inhibitor. binds catalytic site inactivating both fibrinogen-bound and free thrombin. Rapid onset/off. PTT. No antidote. Also inhibits platelet aggregation. Approved for PCI.
Argatroban: class, mechanism, use
Direct-thrombin inhibitor. Synthetic of Arg which inhibits the catalytic site of thrombin. Given for HIT and PCI.
Dabigatran: class, mechanism, uses, antidote
Direct-thrombin inhibitor. Oral, competitive inhibitor of thrombin. Used in nonvalvular a-fib. No antidote. Safe over large range of doses.
Direct Xa Inhibitors: Describe, name the 2
Small molecules that reversibly block the active site. Oral. Rivaroxaban, Apixaban.
Direct Xa inhibitor used in postop DVT prophy, a-fib, DVT/PE
Rivaroxaban
Apixaban uses
Direct Xa inhibitor used in postop DVT prophy, a-fib
