Warfarin (MOA)

Inhibits the hepatic synthesis of vitamin K dependent factors II, VII, IX, X, by inhibiting vit. K epoxide reductase --> prevention of gamma carboxylation of factors

NO effect on already present factors therefore slow onset 

Heparin (MOA)

Protein C and S

Heparins

Chemical make-up: water soluble

kinetics: given IV/SC, short 1/2 life, hepatic/RES metabolism, CAN'T X placenta

Monitor: PTT, partial thromboplastin time

Antidote: protamine sulfate

Uses: rapid anticoagulation for thromboses, emboli, unstable angina, DIC, open-heart surgery

Toxicity: bleeding, osteoporosis, heparin-induced thrombocytopenia (HIT), hypersensitivity

Warfarin

Chemical makeup: small, lipid soluble derivative of vit. K

Kinetics: oral, 98% protein bound, liver metabolism, long 1/2 life, CAN X placenta

Monitor: PT (prothrombin time); INR

Antagonist: Vitamin K, increases cofactor synthesis, can also give fresh frozen plasma

Uses: long-term anticoagulation for thromboses, emboli, post MI, heart valve damage, atrial arrhythmias

Toxicity: bleeding, skin necrosis, drug interactions, teratogenic (bone dysmorphogenesis) 

Enoxaparin

MOA: low-molecular weight heparin that has longer half life

Uses: causes less thrombocytopenia, and enhanced activity of factor Xa

Drug interactions w/ Warfarin

Acidic molecule so when pt takes cholestyramine (or anything that makes stomach less acidic) causes decreased absorption

Extensive/weak protein binding: and can be displaced by MANY other drugs which will increase the free fraciton (ex: ASA, sulfonamide, phenytoins etc.)

Slow hepatic metabolism via P450 so:

inducers --> dec. activity

inhibitors --> inc. activity

Protein C def.

Normally protein C activates S which can then inactivate factors Va and VIIIa

If there is no protein C --> hypercoagulation

Bivalirudin

MOA: thrombin-specific anticoagulant

Uses: w/ ASA in unstable angina when undergoing percutaneous transluminal coronary angioplasty

Thrombolytics (MOA)

aka fibrinolytics, tissue plasminogen activator & streptokinase

Lyse thrombi by catalyzing the formation of the endogenous fibrinolytic plasmin (serine protease) from its precursor plasminogen 

Streptokinase

Uses: IV for short-term EM management of coronary thromboses in MI, DVT, PE, and ischemic stroke

MOA: acts on both bound and free plasminogen (NOT clot specific) depleting circulating plasminogen and factors V and VIII

It is a foreign protein (made from beta hemolytic streptococci) so can be ineffective if had recent infxn where Abs were formed

Alteplase

aka tissue plasminogen activator

Uses: clot specific, acts mainly on fibrin-bound plasminogen

Clinical features of thrombolytics

Effective if EARLY administration (60% decrease in mortality if used w/in 3hrs post MI)

ASA, beta-blockers, and nitrates further dec. mortality and adenosine dec. infarct size

complications can include intracerebral hemorrhage

Antidotes: aminocaproic & tranexamic acids (antifibrinolysins)

Clot formation

1. Platelet adhesion to injury site

2. Activation of platelets by (TxA2, ADP, collagen, 5HT, and thrombin) --> inc. expression of glycoprotein IIb/IIIa receptors

3.  Aggregation of platelets by a cross-linking rxn d/t fibrinogen binding to glycoprotein IIb/IIIa receptors

What increases platelet aggregation

What decreases platelet aggregation

Aspirin

MOA: irreversibly inhibits COX in platelets --> dec. activation

Uses: low doses prevent MI and recurrence, prophylaxis in atrial arrhythmias and TIAs

Ticlopidine and Clopidogrel

MOA: block ADP receptors on platelets --> dec. activation

Uses: alternatives to ASA in TIAs, post-MI, and unstable angina

SE: hemorrhage, leukopenia, and thrombocytopenic purpura

Abciximab, eptifibatide, and tirofiban

MOA: antagonists that bind glycoprotein IIb/IIIa receptors --> dec. aggregation by preventing the cross-linking rxn

Uses: acute coronary syndromes (unstable angina) and postangioplasty