ANTIPLATELET DRUGS DR HEETHAL JAIPRAKASH PHARMACOLOGY Thrombus clot

ANTIPLATELET DRUGS DR HEETHAL JAIPRAKASH PHARMACOLOGY

Thrombus – clot that adheres to a vessel wall Embolus – intravascular clot that floats in blood

Arterial thrombus: v Often occurs in medium sized arteries v Caused by surface lesions on endothelium caused by atherosclerosis v Consists of platelet rich clot Venous thrombus: v Caused by blood stasis, inappropriate activation of coagulation system, defect in normal haemostatic mechanism v Rich in fibrin with few platelets.

Drugs interfering with platelet function: 1. Aspirin 2. Clopidogrel 3. Dipyridamole 4. Ticlopidine 5. GP IIb/ IIIa antagonist - Abciximab

Aspirin : v Acetylates the enzyme cyclooxygenase (COX) and TX-synthetase inactivating them irreversibly. v TXA 2 formation suppressed at very low doses and till new platelets are formed WHY? ? PLATELETS ARE EXPOSED TO ASPIRIN IN THE PORTAL CIRCULATION BEFORE IT GETS DEACETYLATED AND PLATELETS CANNOT SYNTHESIZE FRESH ENZYMES v v Also inhibits PGI 2 synthesis in vessel wall Also inhibits the release of ADP from platelets and their sticking to each other

Dipyridamole: v It is a vasodilator Inhibits phosphodiesterase enzyme and adenosine deaminase Accumulation of c. AMP and adenosine Inhibit platelets aggregation and also stimulate release of PGI 2 v v Given along with aspirin Adverse effects : headache, tachycardia and GIT distress

Ticlopidine: v v v Alters surface receptors on platelets and inhibits ADP as well as fibrinogen-induced platelet aggregation Prevents fibrinogen binding to platelets without modifying GPIIb/IIIa receptor Adverse effects: diarrhoea , vomiting , abdominal pain, headache , tinnitus , skin rash , bleeding , rarely neutropenia , thrombocytopenia and jaundice

Clopidogrel v Similar to Ticlopidine in mechanism , ability to inhibit platelet function and efficacy. v But better tolerated v Adverse effects- diarrhea, epigastric pain, rashes Glycoprotein(GP) IIb/IIIa receptor antagonists: v GP IIb/IIIa –adhesive receptor fibrinogen and von willebrand’s factor through which agonist like TXa 2, ADP etc induce platelet aggregation v Abciximab is an example v It is a Fab fragment of a chimeric monoclonal antibody against GP IIb/IIIa v It is non antigenic v Adverse effects- hemorrhage, thrombocytopenia

Drug Mechanism Uses Aspirin Permanently inhibits COX-1 and COX-2 CAD Stroke-TIAs NSAIDs Reversibly inhibits COX-1 Limited Dipyridamole Inhibits PDE; TIAs increases c. AMP Ticlopidine Clopidrgrel Inhibits ADP Plat. Ag; active metabolite TIAs; Stroke CAD; PVD

Uses of antiplatelet drugs: v Myocardial infarction v Unstable angina v Primary and secondary prevention of MI v Cerebrovascular disease v Coronary bypass implants v Prosthetic heart valves and arteriovenous shunts v Peripheral vascular disease