Anti-Thrombotic Agents Lecture

Objectives

• Describe usage and effects of anti-platelets.
• Outline how anti-platelets affect practice and patient cardiac status and care.

Hemostasis and Thrombosis

Hemostasis

• Biological process to stop bleeding after blood vessel injury.
• Involves substances that promote clot formation (pro-aggregatory) and inhibit clot formation (anti-aggregatory).

Thrombosis Mechanism

• Pro-aggregatory system: Protects from vascular damage by facilitating thrombus formation.
• Anti-aggregatory system: Prevents over-coagulation, limiting clot formation.

Anti-Platelet Agents

• Inhibit platelet function along the platelet activation and aggregation pathway.
• Affect the "white clot" pathway (platelet activation and aggregation).

Thrombus Formation Steps

1. Blood exposed to thrombogenic surface (damaged endothelium).
2. Platelet adhesion, activation, aggregation, with vasoconstriction promotion.
3. Clotting cascade triggered.

Indications for Anti-Platelet Agents

• Unstable angina, stable angina, acute myocardial infarction (MI), post-MI prophylaxis.
• Post coronary artery bypass graft (CABG), coronary angioplasty, coronary stents with other agents.
• Lone atrial fibrillation (<65 years), transient ischemic attacks (TIAs), non-hemorrhagic cerebral stroke.

Aspirin (ASA)

• Blocks formation of thromboxane A2.
• Aspirin history: Derived from willow bark, developed in the 1800s.
• Decreases platelet aggregation by inhibiting COX enzyme.
• Indications: Unstable angina, stable angina, acute MI, post-MI, silent ischemia, CABG, stroke.
• Dosage: 75-325 mg/day (low-dose preferred).
• Adverse effects: Gastric issues, increased bleeding risk.

Factors Reducing Aspirin Effectiveness

• NSAID use (ibuprofen), smoking, post-CABG state.
• High norepinephrine levels, hyperlipidemia, genetic variances.

Other Benefits of Aspirin

• Pain relief, anti-inflammatory effects, fever relief.

Thianopyridines

• Clopidogrel: Inhibits ADP-induced platelet activation.
  • Indications: Reduction of atherosclerotic events, acute coronary syndromes, aspirin resistance.
  • Adverse effects: Dyspepsia, abdominal pain, bleeding.
  • Interaction: Reduced effectiveness with pantoprazole.
• Ticagrelor: Inhibits platelet aggregation, used with low-dose aspirin.
  • Adverse effects: Similar to clopidogrel, interaction with atorvastatin.

Dipyridamole

• Often used with aspirin or warfarin.
• Inhibits platelet aggregation by adenosine-like peptide buildup.
• Use: Prevent thrombosis with prosthetic valves, reduce stroke risk.
• Adverse effects: Risk of ischemia and angina due to coronary steal.

GP2b/3a Inhibitors

• Block final step of platelet aggregation.
• Effective anti-platelet agents, prevent formation of hemostatic plug.
• Receptor Antagonists: Abciximab, Eptifibatide, Tirofiban.
  • Adverse effects: Prolonged bleeding time, mucosal bleeding, especially with heparin.

Abciximab (Reopro)

• Indicated for acute coronary syndrome, PCI.
• Dosage and administration depend on patient condition (unstable angina, STEMI).
• Adverse effects: Increased bleeding, thrombocytopenia.

Eptifibatide (Integrillin)

• Used in ACS patients undergoing PCI.
• Dosage: Bolus and infusion, adjusted for discharge.
• Adverse effects: Similar to abciximab, requires renal dose adjustment.

Tirofiban (Aggrastat)

• Administered during PCI.
• Adverse effects: Similar to eptifibatide, renal adjustment required.

Recap and Closing

• Importance of aspirin in MI prevention due to decreased platelet aggregation.
• Combined use of aspirin and clopidogrel post-MI for enhanced protection.
• End of presentation on anti-thrombotic agents.