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Antiplatelet Agents
Frederick Villamena, PhD
Associate Professor of Pharmacology
College of Medicine
The Ohio State University
Block Objective
Describe
• the mechanisms of action• indications• and major side effects of
drugs affecting platelet activation and aggregation.
Objectives
Identify
the main molecules responsible in platelet
activation and aggregation.
Classify and name
antiplatelet agents according to their
mechanisms of actions.
Identify
the properties, applications,
pharmacokinetics, toxicity, and contraindications of
various antiplatelet drugs.
References
Lilly, L. Pathophysiology of Heart Disease, 5th ed. 2010. Chapter 17, pp. 423-427.
Harvey, R.A. and Champe, P. C. Pharmacology, 5th ed. Lippincott Illustrated Reviews.
Mechanism of Platelet Activation and Aggregation
Lippincott Williams and Wilkins
Platelet Aggregation Inhibitors
To decrease the formation or signaling action that promote aggregation.
Regulation of platelet activating agents that promote binding of GP IIb/IIIa receptor to fibrinogen.
COX-1 Inhibitor
Aspirin is the most commonly used one and is orally administered. Used to prevent thrombosis in atherosclerotic disease of coronary
and peripheral vessels. Used in treatment of transient cerebral ischemia, reduce
recurrence of MI and decrease mortality in MI patients. Side effects are GI-related, allergy and bleeding.
ADPTXA2
GP IIb/IIIa receptors activation
fibrinogenCa2+
thrombin
ADP, TXA2 synthesis
prostaglandin H2
arachidonic acid
COX-1
TXA2
ADP inhibitors
Antiplatelet substitutes in patients allergic to aspirin.
Orally administered.
Thienopyridine-based drugs: ticlopidine, clopidogrel, and prasugrel
Ticlopidine is rarely used now. Clopidogrel is an approved pro-drug for prevention of
atherosclerotic events from MI, stroke, and peripheral arterial disease. Prevents thrombotic events during and after percutaneous coronary intervention (PCI) with or without stent.
Prasugrel is a newer ADP inhibitor. More effective than clopidogrel in reducing cardiovascular disease death, nonfatal heart attack and stroke.
Ticagrelor (not a thienopyridine) is used to prevent thrombosis during PCI with stent replacement. Co-administered with aspirin (75-150 mg). Reduced efficacy at higher ASA doses.
Side effects of thienopyridines: bleeding,
indigestion, and diarrhea.
Potentially life-threatening hematologic effects in small number of patients with the
use of ticlopidine.
Fibrinogen (GP IIb/IIIa) receptor inhibitors
Administered by IV injection. Abciximab is a monoclonal antibody
injected with either heparin or aspirin as an adjunct to percutaneous coronary intervention (angioplasty).
Tirofiban (synthetic nonpeptide) and eptifibatide (synthetic peptide) decrease incidence of thrombotic complications from acute coronary syndromes.
All can cause bleeding and thrombocytopenia as adverse side affects.
Phosphodiesterase inhibitor
Cilostazol is an oral antiplatelet agent with vasodilating activity. FDA approved to reduce claudication in peripheral artery disease (PAD). Highly metabolized. Contraindicated in patients with congestive heart failure.
ATP cAMP degradationphosphodiesterase
elevated level cAMP
Ca2+ platelet aggregation
NO and prostacylcin from endothelium
Comparison of Major Antiplatelet Drugs
Drugs
Mechanism of action
Indications
Route of administration
Adverse/Side effect
COX-1 inhibitors
TXA2 synthesis via COX-1 inhibition
Prevent thrombosis in atherosclerotic
disease
Oral
Allergy/Bleeding
ADP Inhibitors
ADP receptors inhibition
Prevent thrombosis in CAD, PAD
Prevent stent thrombosis-PCI
Oral
Bleeding (contraindicated in hepatic diseases)
IIb/IIIa Receptor inhibitors
GP IIb/IIIa receptor blockage
Acute coronary syndromes where
angioplasty is planned
IV
Bleeding
Phosphodiesterase inhibitors
Inhibition of cAMP degradation via PDE inhibition
Used in peripheral arterial disease
Oral
Contraindicated in patients with heart
failure
Antiplatelets Quiz
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