Pharm 3 List Anticoagulant And Thrombolytic Drugs

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Heparin

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Indirect Thrombin inhibitor - interact at antithrombin III and Xa
Heparin is a heterogeneous mixture of sulfated mucopolysaccharides

Inhibits Factors IXa, Xa, and IIa (thrombin) in the intrinsic and common pathways.

Uses:
1. Tx of venous thrombosis
2. Tx of pulmonary embolism
3. Tx of acute myocardial infarction d/t rapid action by IV
4. used in surgery requiring cardiopulmonary bypass with pts with DIC
5. Effective in tx of unstable angina (LMW)

LMW doesn’t require laboratory monitoring
Initiated with bolus injection followed by infusion pump dosing
s.c. administration used for long term tx of pts who cannot take warfarin (Pregnancy)
Monitored with aPTT

SEs:
Tox: Bleeding
Heparin-induced thrombocytopenia

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Fondaparinux (Lovenox)

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Uses:
1. thromboprophylaxis of patients p/t hip or knee surgery for pulmonary embolism and DVT

Along with LMW heparin can be administered s.c. daily and do not require monitoring

SEs:
Tox: Bleeding

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Protamine

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Antidote for heparin overdose

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Hirudin (Lepirudin/Refludan)

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Bivalent, specific, irreversible thrombin inhibitor from leech saliva

Uses: Tx of pts with heparin-induced thrombocytopenia

Administered IV
Dose adjusted depending on aPTT

SEs:
Use cautiously in pts with renal failure (can accumulate and cause bleeding in these pts)
Antihirudin antibodies that can cause a paradoxical increase in aPTT

Monitor aPTT

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Bivalirudin (Angiomax)

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Bivalent inhibitor of thrombin

Uses: Used as an alternative to heparin in patient undergoing coronary angioplasty

Administered IV

SEs:
Use cautiously in pts with renal failure (can accumulate and cause bleeding in these pts)
Antihirudin antibodies that can cause a paradoxical increase in aPTT

Monitor aPTT

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Argatroban

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Small molecule thrombin inhibitor

Used as an alternative to hirudin/lepirudin for prophylaxis or tx of patients with heparin-induced thrombocytopenia

SEs:
Use cautiously in pts with renal failure (can accumulate and cause bleeding in these pts)
Antihirudin antibodies that can cause a paradoxical increase in aPTT

Monitor aPTT

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Warfarin (Coumadin)

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Oral Thrombin Inhibitors
Inhibits the vitamin K dependent synthesis of biologically active forms of the calcium-dependent clotting factors prothrombin, VII, IX and X as well as the regulatory factor protein C
Blocks the gamma-carboxylation of glutamate residues in coagulation factors -> biologically inactive

Uses:
1. Prevent progression or recurrence of acute DVT or pulmonary embolism after initial course of heparin
2. Prevent venous thromboembolism in pts undergoing surgery
3. Prevent embolization in pts with acute MI, prosthetic heart valves or chronic afib

Administered as sodium salt
100% bioavailability
Slower acting than heparin
Use with caution in pts with congenital coagulation factor deficiency, thrombocytopenia, hepatic or renal insufficiency
DO NOT USE IN PREGANCY
Watch INR

SEs:
Pts can develop warfarin resistance
Barbiturates and rifampin can decrease efficacy
Aspirin and cephalosporins augment the effects

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Digabatran (Pradaxa)
Rivaroxiban
Apixaban

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New drugs... don’t have to know

Thrombin/Factor X inhibitors

Some reduce the risk of stroke in patients with atrial fibrillation.

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t-PA (Reteplase, Activase, Tenecteplase)


Tissue plasminogen activator

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Fibrinolytic
t-PA binds to fibrin via lysine binding sites at its amino terminus and activates bound plasminogen much more rapidly than it activates plasminogen in circulation

Uses:
1. Effective in lysing thrombi during tx of acute MI via IV
2. Pulmonary embolism and severe DVT

Clearance via hepatic metabolism
t1/2 5-10 minutes
Angioplasty, and stent placement probably better now

SEs: hemorrhage

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Streptokinase (streptase)

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Produced by beta hemolytic streptococci

forms a stable complex with plasminogen which produces a conformational change that exposes the active site on plasminogen that forms free plasmin

Not used much anymore

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Aminocaproic Acid (Amicar)

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potent inhibitor of fibrinolysis - blocks interaction between fibrin and plasmin

Can reverse states associated with excessive fibrinolysis

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Aspirin

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antiplatelet drug - blocks platelet aggregation and vasoconstriction by inhibiting synthesis of thromboxane A2. Inhibits this by acetylating a serine residue near the active site of COX1 which produces precursor to A2

Uses:
1. Blocks platelet interaction with fibrinogen
2. May be given after MI
3. Prevent MI, stroke, blood clots

SEs:
Higher doses increase tox
Increased risk of UGI bleeds

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Dipyridamole (Persantine)

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Vasodilator that in combo with warfarin inhibits embolization from prosthetic heart valves, strokes or TIAs

In combo with warfarin for postop prophylaxis of thromboemboli

SEs:
N/V/D
Severe leukopenia

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Clopidogrel (Plavix)

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Platelet adenosine diphosphate (ADP) receptor antagonist inhibiting platelet activation

Blocks platelet interaction with fibrinogen
Used with aspirin after angioplasty

SE: Less toxicity

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Ticlopidine (Ticlid)

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Platelet adenosine diphosphate (ADP) receptor antagonist inhibiting platelet activation

Reduced risk of thromboembolic stroke

SEs:
N/V/D
Severe leukopenia

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Abciximab (Reopro)

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Inhibit platelet aggregation by blocking binding of Glycoprotein IIb/IIa platelet-surface integrin to fibrinogen
Fab fragment of a humanized monoclonal antibody directed against the integrin receptor

Uses:
1. used with percutaneous angioplasty for coronary thrombosis
2. Used with aspirin and heparin to prevent restenosis, MI and death

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Eptifibatide (Integrilin)

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Inhibit platelet aggregation by blocking binding of Glycoprotein IIb/IIa platelet-surface integrin to fibrinogen
A cyclic peptide inhibitor of the fibrinogen binding site on integrin receptor alphaIIb/beta3

Uses:
1. IV for tx of acute coronary syndrome and angioplastic coronary interventions
2. Reduce MI and death

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Tirofiban (Agrrastat)

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Inhibit platelet aggregation by blocking binding of Glycoprotein IIb/IIa platelet-surface integrin to fibrinogen
A nonpeptide, small molecule inhibitor of alphaIIb/beta3

Uses: Effective in non Q-wave MI and unstable angina

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Cilostazol

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Antiplatelet drug

not tested