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ANTIPLATELET DRUGS
DR HEETHAL JAIPRAKASHPHARMACOLOGY
Thrombus – clot that adheres to a vessel wall
Embolus – intravascular clot that floats in blood
Arterial thrombus:v Often occurs in medium sized arteriesv Caused by surface lesions on endothelium
caused by atherosclerosisv Consists of platelet rich clot
Venous thrombus:v Caused byà 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-synthetaseà
inactivating them irreversibly.v TXA2 formation suppressed at very low doses and till new platelets
are formedàWHY????
v Also inhibits PGI2 synthesis in vessel wallv Also inhibits the release of ADP from platelets and their sticking to
each other
PLATELETS ARE EXPOSED TO ASPIRIN IN THE PORTAL CIRCULATION BEFORE IT GETS DEACETYLATED AND PLATELETS CANNOTSYNTHESIZE FRESH ENZYMES
Dipyridamole: v It is a vasodilator
v Given along with aspirinv Adverse effects : headache, tachycardia and GIT distress
Inhibits phosphodiesterase enzyme and adenosine deaminase
Accumulation of cAMP and adenosine
Inhibit platelets aggregation and also stimulate release of PGI2
Ticlopidine:v Alters surface receptors on platelets and inhibits ADP as
well as fibrinogen-induced platelet aggregationv Prevents fibrinogen binding to platelets without
modifying GPIIb/IIIa receptorv Adverse effects: diarrhoea , vomiting , abdominal pain,
headache , tinnitus , skin rash , bleeding , rarely neutropenia , thrombocytopenia and jaundice
Clopidogrelv 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 for fibrinogen and von
willebrand’s factor through which agonist like TXa2, ADP etc induce platelet aggregation
v Abciximab is an examplev It is a Fab fragment of a chimeric monoclonal antibody
against GP IIb/IIIav It is non antigenicv Adverse effects- hemorrhage, thrombocytopenia
CADStroke-TIAs
Permanently inhibits COX-1 and COX-2
Aspirin
TIAs;StrokeCAD;PVD
Inhibits ADP PlatAg;activemetabolite
TiclopidineClopidrgrel
TIAsInhibits PDE; increases cAMP
Dipyridamole
LimitedReversibly inhibits COX-1
NSAIDs
UsesMechanismDrug
Uses of antiplatelet drugs:v Myocardial infarctionv Unstable anginav Primary and secondary prevention of MIv Cerebrovascular diseasev Coronary bypass implantsv Prosthetic heart valves and arteriovenous shuntsv Peripheral vascular disease
