Pharm - Hemostasis (Block 1)

Front 1

Glycoprotein IIb/IIIa Inhibitors

Back 1

ACUTE Anti-Platelet Aggregation

Inhibits IIb/IIIa Complex (Integrin) Receptor on Platelets for Fibrinogen (2 Binding Sites)

Large, so must be administered Parenterally!

Either Antibodies or Peptides:
1) Antibody = Abciximab (ReoPro) --> Binds and Sterically Interferes with Fibrinogen Binding (Lasts 24-48 Hours)

2) Peptide = Eptifibatide (Integrelin) --> Directly Competes with Fibrinogen Binding (Cleared Rapidly)

Uses:
1) Prevent Thrombosis after PCI
2) ACS

Side Effects:
1) BLEEDING! (More Rapidly Reversed w/Eptifibatide since it is rapidly cleared)

Front 2

Acetylsalicylic Acid (ASA) (Aspirin)

Back 2

CHRONIC Anti-Platelet Activation

Low Dose (60-160 mg), Once per Day (Lasts ~1-2 Weeks, depends on life of platelets they effect)

@ Low Doses, Irreversible Inhibitor of PLATELET COX, Blocking Production of TxA2 (which normally promotes platelet activation/aggregation)

Uses:
1) CAD at risk for MI
2) Carotide Artery or Cerebral Artery Atherosclerosis at risk for Transient Ischemic Attacks (TIAs) or Ischemic Stroke
3) Arterial Prosthesis, Valvular Heart Disease, other Conditions with Damaged Endothelium

Side Effects:
1) @ Low Doses = RARE

Front 3

Clopidogrel (Plavix)

Back 3

CHRONIC Anti-Platelet Activation

Alternative to ASA, more Efficacious

Given Orally

Inhibits ADP Receptor and ADP-Dependent Platelet Aggregation

Side Effects:
1) Bleeding when in Combo with ASA
2) Thrombotic Thrombocytopenic Purpura (TTP) - RARE

Ticlopidine is a related drug with MORE side effects!

Front 4

TPA

Back 4

Thrombolytics

Protein normally Produce by Endothelial Cells, thus produce via Recombinant DNA Technology = EXPENSIVE!

Administered IV (Cleared by Liver). Free TPA Half Life = 5-10 Mins. Fibrin bound TPA can be active for Hours.

Relatively Selective to Plasminogen BOUND to Fibrin!

Uses:
1) Acute MI
2) Stroke

Side Effects:
1) Hemorrhage! Increased if used in combo with Anti-Coags or Anti-Platelet Therapy

Front 5

Streptokinase

Back 5

Thrombolytics

Protein produce by B-Hemolytic Strep

MUCH CHEAPER than TPA

Less Selective than TPA for Fibrin bound Plasminogen. This can lead to both Thrombolysis and Degradation of Fibrinogen, can cause Hemorrhage due to Hypofibrinogenemia

Since most pts have Anti-Steptokinase Abs from previous infection, loading dose is given to saturate Abs.

Longer Half Life than TPA (40-80 Mins)

Urokinase is Produce by Renal Epithelial Cells. Like Streptokinase, it is also NON-Selective. It is also EXPENSIVE!

Front 6

Aminocaproic Acid

Back 6

Anti-Fibrolytic

Inhibits Plasminogen Binding to Fibrin

Uses:
1) Blocks EXCESSIVE Fibrinolysis

Front 7

Heparin

Back 7

ACUTE Anti-Coagulants

Sulfated Proteoglycan produced by Mast Cells

Binds to Anti-Thrombin, Increasing Its Inhibition of Activated Coag Factors (Extrin and Intrin)

Must be given Parenterally

Onset is immediate, cleared rapidly by Macrophages.

Short Half Life. May be Increased in Pts with Cirrhosis and Chronic Renal Failure!

Does NOT Cross Placenta!

Goal = PTT 1.5 - 2.5 X Normal

Side Effects:
1) Hemorrhage
2) Immune Thrombocytopenia (7-14 days after initiation of therapy)

Low Molecular Weight Heparin = Enoxaparin (Lovenox) --> Can Still cause Immune Thrombocytopenia!

Synthetic Heparin = Fondaparinux --> Induces Factor Xa Inhibition. Does NOT cause Immune Thrombocytopenia. Used for Prolonged Prophylaxis.

Antidote = Protamine Sulfate!

Front 8

Warfarin (Coumadin)

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CHRONIC Anti-Coagulants

Competitive Inhibitor of Vit K Epoxy Reductase (VKOR), Depleting Cellular Stores of Active Vitamin K

Can be taken by Mouth

Onset is delayed, full affect takes ~7-10 days.

Goal = INR (Normalized PT) 2.0 - 3.0 X Normal

CROSS THE PLACENTA! Potent Teratogen!

Extensively Protein Bound, Metabolized by CYP2C9 in Liver.

Drug-Drug Interactions:
1) Antibiotics (Deplete Vitamine K) --> Increase Warfarin Action
2) Sulfinpyrazone, Cimetitidine, Allopurinal (Displace Warfarin from Binding Sites) --> Increase Warfarin Activity
3) Barbiturates, Phenytoin (Increase Hepatic Microsomal Enzymes) --> Decrease Warfarin Activity

Side Effects:
1) Hemorrhage
2) Necrotic Ulcers of the Skin (Occasionally)

Antidote:
1) Administration of Vitamin K (can take hours or days)
2) Emergency Situation: Infusion of Fresh Plasma or Clotting Factor Concentrates