drug tx in thrombosis

Question 1

Unfractionated Heparin

Answer 1

• indirect thrombin inhibitor
• binds antithrombin –> formation of antithrombin-coagulation factor complex (Xa, IIa)
• inhibits Xa and thrombin (IIa)
• given initially (immediate-acting, short half-life, parenteral) followed by warfarin
• unpredictable dosing because it binds to everything –> need to monitor via PTT (want 2-2.5X normal value)
• adverse side effects: HIT, osteoporosis, bleeding
• reversed by protamine

Question 2

Low Molecular Weight Heparin

Answer 2

• indirect thrombin inhibitor
• mostly inihibits Xa, less effective against thrombin
• (w/o the long tail the antithrombin complex can’t bind thrombin)
• predictable dose-response –> less need to monitor but if you have to monitor via heparin assay (rather than PTT)
• longer half-life
• lower risk of inducing HIT
• less effective reversal with protamine

Question 3

Dalteparin (Fragmin)

Answer 3

LMWH

-“parin” = LMWH

Question 4

Enoxaparin (Lovenox)

Answer 4

• LMWH
• drug of choice in pregnancy

“-parin” = LMWH

Question 5

Tinzaparin (Innohep)

Answer 5

• LMWH

“-aprin” = LMWH

Question 6

Fondaparinux

Answer 6

• Indirect thrombin inhibitor
• synthetic polysaccharide that binds the active site of antithrombin
• inhibits Xa (ineffective against thrombin!)
• given for HIT patients
• no antidote!

Question 7

image of mech of action of unfractionated heparin, LMWH and fondaparinux

Answer 7

• UFH binds antithrombin –> formation of antithrombin complex (Xa, IIa)
• LMWH cant bind thrombin
• fondaparinux doesn’t bind thrombin either

Question 8

warfarin (coumadin)

Answer 8

• Vitamin K antagonist –> blocks vitamin K-dependent carboxylation of factors II, VII, IX, X, Protein C and S
• slow onset (often preceded by heparin)
• oral, long-term use
• may induce venous thrombosis at onset of tx because it inhibits anticoagulants protein C and S
• drug interactions –> enhanced metab.
• monitored by PT/ INR
• reversed by Vit K, factor concentrates or FFP
• contraindicated in pregnancy (teratogenic!)

Question 9

direct thrombin inhibitors

Answer 9

• Lepirudin, Bivalirudin (Angiomax), Argatroban and Dabigatran
• inactivate fibrinogen-bound and unbound thrombin; irreversible
• parenteral administration with rapid onset
• monitored by PTT
• no antidote!

Question 10

Lepirudin

Answer 10

direct thrombin inhibitor

Question 11

Bivalirudin (angiomax)

Answer 11

direct thrombin inhibitor

Question 12

Argotroban

Answer 12

direct thrombin inhibitor

Question 13

Dabigatran (Pradaxa)

Answer 13

direct thrombin inhibitor (oral)

Question 14

direct Xa inhibitors

Answer 14

• Rivaroxaban and Apixaban (have “X” in name)
• oral
• no methods to assess levels, no antidote

Question 15

streptokinase

Answer 15

• Fibrinolytic (thrombolytic)
• lyses already formed clots by activating circulating plasminogen
• not clot specific

Question 16

Urokinase

Answer 16

• Fibrinolytic/thrombolytic
• lyses alreadly formed clots by activating circulating plasminogen
• serine protease

Question 17

Reteplase and Tenecteplase

Answer 17

• tissue plasminogen activator (t-PA) derivatives
• lyse already formed clots by activating fibrin-bound plasminogen
• more clot specific –> less systemic activation

Question 18

anticoagulants

Answer 18

• used for venous thrombosis
• Heparins (UFH, LWMH, Fondaparinux)
• Vit K antags (warfarin)
• Direct thrombin inhibs (Dabigatran, Bivalirudin, Argatroban, Lepirudin)
• Direct Xa inhibs (Rivaroxaban)

Question 19

fibrinolytic drugs

Answer 19

• used for acture thrombosis
• streptokinase, urokinase, t-PA

Question 20

antiplatelet drugs

Answer 20

• used for arterial thrombosis
• asprin, clopidogrel, prasugrel, abciximab, eptifibatide, tirofiban

Question 21

aspirin

Answer 21

• PGs have opposing effects on platelets (pro-coag) and endothelial cells (anti-coag)
• low-dose baby asprin has greater effect on platelet COX-1 (new protein is continously being made in endothelial cells but no in anucleate platelets) –> higher doses affect endothelial cell COX-1

Question 22

dipyridamole

Answer 22

• antiplatelet drug (weak effect)
• phosphodiesterase inhibitor –> increases platelet cAMP

DIpyridamole –> phosphoDIesterase inhib

Question 23

Clopidogrel (plavix)

Answer 23

• anti-platelet drug
• inhibits platelet ADP receptor
• irreversible binding –> antithrombotic effect lasts up to 10 days and can only be reversed with platelet infusion
• give prasugrel (works by same mech but activiated by different P450) if resistant

Question 24

Abciximab

Answer 24

• antiplatelet drug
• MAb against GP IIb/IIIa (fibrinogen receptor)
• may illicit immune response

Question 25

Eptifibatide (Integrilin) and Tirofiban (Aggrastat)

Answer 25

* antiplatelet drugs * fibrinogen analog which competes with endogenous fibrinogen and vWF binding to IIb/IIIa integrilin has integrity so it will compete fairly with fibrinogen