atherosclerotic plaques

surgical injury to vessels

acute inhibition of platelet aggregation by blockade of platelet membrane fibrinogen receptors

used to prevent thrombosis following PCI and to treat ACS

• fibrinogen has two IIb/IIIa binding sites
• Gp IIb/IIIa is an integrin w/ αIIb/β3 chains
• inihibition blocks fibrinogen binding and results in immediate blockade of platelet fxn
• Must be given parenterally (too large to be absorbed)

• monoclonal antibody
• binds to IIb/IIIa and sterically interferes w/ fibrinogen binding
• given by bolus injection followed by infusion
• immediate onset of action, persists for 1-2 days
• prevent PCI thrombosis and unstable angina
• bleeding is the main complication

• peptide
• binds to IIb/IIIa and competes w/ fibrinogen
• parenterally by bolus + infusion
• rapid onset of action but cleared so rapidly it is only effective during infusion
• used in both PCI and unstable angina
• bleeding is main side effect

• irreversible inhibitor of COX, when low dose it preferentially blocks platelet production of thromboxane A2 w/o inhibiting endothelial prostacyclin I2
• net effect: inhibit platelet activation and decrease platelet function

• endothelial cells have nucleus so can regenerate COX de novo, but platelets cannot

once-a-day low dose for inc risk of arterial thrombi

1. coronary artery disease
2. cerebral artery atherosclerosis (TIA risk)
3. arterial prosthesis or damaged endothelium

60-160 mg per day

ASA anti-platelet activity lasts for 1-2 weeks

1. inhibits ADP receptor thus ADP-dependent platelet aggregation
2. used as an alternative or in combo w/ ASA
3. SE: bleeding when used in combo w/ ASA
4. ORAL for long term therapy
5. For acute situations, give a loading dose

For acute arterial thrombosis

must be given by IV infusion and only lasts for an hour or so

Frequently used in combo w/ anti-platelets/coags

• protease normally produced by endothelium
• binds to fibrin and activates plasminogen
• selective for plasminogen bound to fibrin
• used for acute MI and stroke
• IV prep
• cleared in 5-10 mins, can stay bound to fibrin clot for hours
• SE: hemorrhage!

• produced by b-hemolytic strep that promotes activation of plasminogen
• binds to free or bound plasminogen and auto-activates it
• increases risk of hemorrhage
• Many patients have antibodies to it so must give a loading dose then IV infusion
• 40-80 min half life

plasminogen activator secreted by renal epithelial cells

non-selective and expensive

antidote to excessive fibrolysis

inhibits plasminogen binding to fibrin

1. sulfated proteoglycan
2. produced by mast cells
3. high molecular weight polymers

1. binds to anti-thrombin, increasing its activity
2. causes immediate inhibition of coagulation cascade
3. blocks extrinsic (IXa, Xa, IIa)
4. blocks intrinsic (XIa, XIIa, kallikrein

1. given parenterally (LMWH via subcutaneous)
2. onset is immediate, cleared rapidly
3. does NOT cross the placenta
4. Goal of therapy is 1.5 - 2.5x normal PTT

1. hemorrhage is most common
2. immune thrombocytopenia in longterm therapy

• fondaparinux - synthetic heparin that blocks factor Xa inhibition --> good for long-term prophylaxis
• Enoxaparin - improved thrombokinetics
• Subcutaneous admin used prophylactically in hospitalized patients

Rivaroxaban is a direct inhibitor

given ORALly for long-term anti-coagulation

prevents DVT

1. Factors VII, IX, X, II are modified by adding γ-carboxy groups to glutamate residues
2. Vitamin K is a co-factor in this reaction
3. after rxn vit K needs to be converted back by a reductase enzyme
4. Warfarin is a competitive inhibitor of this reductase
5. depletes active vitamin K

1. taken ORALly for long-term therapy
2. onset of delay, so full effects not present til a week after starting therapy
3. goal is to increase INR to 2-3x goal
4. crosses the placenta

metabolized by CYP2C9

some patients have variants that make them more or less susceptible to therapy so need to do a diagnostic test before giving medicine

1. bad interaction if taking drugs that effect vit K, protein binding, or warfarin metabolism
2. antibiotics deplete Vit K, thus ↑warfarin action
3. drugs that increase hepatic microsomal enzymes (barbiturates) decrease warfarin anti-coagulation
4. if they displace warfarin from proteins it will increase warfarin activity

Long term anti-coagulation

1. pulmonary embolism 2° to thrombophlebitis
2. chronic a-fib
3. prosthetic valves, stents, vessel grafts

it is TERATOGENIC

reversed by administration of vitamin K

in emergency can infuse fresh plasma or clotting factors