Drug Therapy in Thrombosis

Question 1

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

Answer 1

Anticoagulants

Question 2

Immediately acting, short half life, parenteral drug followed by what oral. long half life, slowly acting drug; both for anticoagulation

Answer 2

Heparin. Warfarin

Question 3

Serious complication of heparin? Of warfarin? Are there antidotes?

Answer 3

HIT. Skin necrosis. Yes

Question 4

Describe the coagulation cascade please

Answer 4

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.

Question 5

Heparin is an indirect [ ] inhibitor. It binds to [ ] which potentiates formation of inactivating [ ]-coagulation factor complexes. What factors does it combine with to inactivate?

Answer 5

Thrombin. Antithrombin, antithrombin. IIa and Xa.

Question 6

Thx effectiveness of heparin is monitored by measuring the [ ] which should be [ ] times the normal value

Answer 6

PTT; 2-2.5.

Question 7

A highly basic peptide that binds heparin to treat this adverse side effect

Answer 7

Protamine sulfate. Bleeding

Question 8

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.

Answer 8

Std (unfractionated) heparin

Question 9

Long-term use of heparin causes what?

Answer 9

Osteoporosis

Question 10

Hallmark of LMWH. Name 3 diff preparations. Half-life compared to std.

Answer 10

Inhibit thrombin less effectively than factor Xa. Dalteparin, Enoxaparin (Lovenox, best in preg), Tinzaparin. Longer t1/2.

Question 11

LMWH monitoring is done using what assay?

Answer 11

Heparin assay (anti-factor Xa assay) rather than PTT.

Question 12

Fondaparinux binds what? Given when? Antidote?

Answer 12

Binds active site of AT, inhibits Xa. Long half-life. Can be given in HIT. CANNOT be reversed when bleeding occurs.

Question 13

Warfarin is a [ ], aka oral anticoagulant. It blocks the [ ] carboxylation of what factors, preventing their activity.

Answer 13

Vit-K antagonist. Vit-K-dependent y-carboxylation of II, VII, IX and X (and Protein C&S).

Question 14

Displacement of [ ]-bound warfarin by other meds increases the free conc and its anticoag activity.

Answer 14

Albumin

Question 15

Long-term antibiotic therapy has what affect on warfarin’s anticoagulant activity? Warfarin metabolism is enhanced by what?

Answer 15

Decreases vitamin K and thus increases anticoagulation. Drug-induced increases in hepatic P450 activity (e.g barbiturates)

Question 16

Measure warfarin effectiveness with what?

Answer 16

PT/INR

Question 17

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?

Answer 17

Balance tipped to pro-coagulation resulting in vascular thrombosis and skin necrosis

Question 18

Warfarin therapy may be reversed, in ascending order of rapidity, by what?

Answer 18

Stopping the drug, administering Vit K, Prothrombin cpx concentrate (Kcentra: II, VII, IX, X, PrC&S), fresh frozen plasma.

Question 19

Bivalirudin: class, mechanism, speed, monitoring, antidote, uses

Answer 19

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.

Question 20

Argatroban: class, mechanism, use

Answer 20

Direct-thrombin inhibitor. Synthetic of Arg which inhibits the catalytic site of thrombin. Given for HIT and PCI.

Question 21

Dabigatran: class, mechanism, uses, antidote

Answer 21

Direct-thrombin inhibitor. Oral, competitive inhibitor of thrombin. Used in nonvalvular a-fib. No antidote. Safe over large range of doses.

Question 22

Direct Xa Inhibitors: Describe, name the 2

Answer 22

Small molecules that reversibly block the active site. Oral. Rivaroxaban, Apixaban.

Question 23

Direct Xa inhibitor used in postop DVT prophy, a-fib, DVT/PE

Answer 23

Rivaroxaban

Question 24

Apixaban uses

Answer 24

Direct Xa inhibitor used in postop DVT prophy, a-fib

Question 25

Is there a need to monitor direct Xa inhibitors?

Answer 25

No

Question 26

What do the oral direct inhibitors of Xa and IIa have in common?

Answer 26

No methods to assess levels and no specific antidotes.

Question 27

Lyses clots by activating circulating plasminogen

Answer 27

The recombinant tPA named Alteplase

Question 28

Reteplase and Tenecteplase have what advantage over Alteplase?

Answer 28

More specific activation of fibrin-bound plasminogen with less systemic activation

Question 29

Fibrinolytic drugs lyse already formed clots and are used in patients with?

Answer 29

acute MI, acute arterial occlusion (ischemic stroke), central DVT, multiple PE.

Question 30

Antiplatelet drugs function to prevent and treat?

Answer 30

Arterial thrombosis (MI, stroke). Also used in PCI (angioplasty, stent).

Question 31

Irreversibly inhibits platelet COX and prevents formation of TXA2 required for optimal aggregation?

Answer 31

Aspirin

Question 32

What happens to the effect of aspirin at high doses?

Answer 32

Effect on endothelial cells becomes greater and thus PGI2 (prostacyclin) release is decreased longer than transiently now. The inhibition of platelet aggregation is lost from PGI2, mitigating the effects on TXA2 inhibition.

Question 33

Dipyridamole: class, use, increases what which has what affect

Answer 33

Phosphodiesterase inhibitor. Secondary stroke prevention, weak antiplatelet effect. Increases cAMP and cGMP which decreases aggregation.

Question 34

Clopidogrel (Plavix): mech, rare S.E., how to reverse antithrombotic effect

Answer 34

Reduces platelet aggreg by inhibition of platelet ADP receptors (irreversible P2Y12 receptors blocker). TTP. Only by platelet transfusion.

Question 35

Monoclonal Ab directed against GPIIb/IIIa. S.E. of this drug which limits repeated use.

Answer 35

Abciximab. May elicit an immune response.

Question 36

Eptifibatide and tirofiban are [ ] analogs which compete with endog [ ]- and [ ]-binding to IIb/IIIa

Answer 36

Fibrinogen analogs; fibrinogen and vWF

Question 37

Mech of action of the direct thrombin inhibitors. Do they have antidotes?

Answer 37

The table says they all inactivate fibrinogen-bound AND unbound thrombin. No