antiplatelet and fibrinolytics
TRANSCRIPT
ANTIPLATELET DRUGS& FIBRINOLYTICS
DR. K MUKHOPADHYAYASSISTANT PROFESSOR
ESI-PGIMSR
ANTITHROMBOTIC DRUGS
Fibrinolytics
REFLEX VASOCONSTRICTION
PRIMARY HEMOSTASIS
SECONDARY HEMOSTASIS
THROMBUS AND ANTITHROMBOTIC EVENTS
Platelet Adhesio
n
Platelet Aggregatio
n
Platelet Activatio
n
ANTI-PLATELETDRUGSMECHANISM
• COMPLETE INACTIVATION OF PLATELET COX-1 IS ACHIEVED WITH A DAILY ASPIRIN DOSE OF 75 MG.
HIGHER THE DOSE MORE EFFICACY ???
NO• AT HIGH DOSES (1 G/D), IT ALSO INHIBITS
COX-2 (RESPONSIBLE FOR SYNTHESIS OF PROSTACYCLIN, A POTENT INHIBITOR OF PLATELET AGGREGATION)
ASPIRIN
ADP RECEPTOR
P2Y1- induces a shape change and aggregation.
P2Y12 - inhibits adenylyl cyclase. So causes Platelet activation
- increases Adhesiveness of platelets
VORAPAXAR
P2Y12
P2Y1
TICLOPIDINE
A PRODRUG (ACTIVATED BY HEPATIC CYP) THAT INHIBITS THE P2Y12 RECEPTOR BY FORMING A DISULFIDE BRIDGE IN THE EXTRACELLULAR REGION OF THE RECEPTOR
SHORT T1/2 BUT LONG DURATION
NEUTROPENIA, FATAL AGRANULOCYTOSIS WITH THROMBOCYTOPENIA
CLOPIDOGREL
• IT IS AN IRREVERSIBLE INHIBITOR OF PLATELET P2Y12 RECEPTORS
• IT IS MORE POTENT AND HAS A MORE FAVORABLE TOXICITY PROFILE THAN TICLOPIDINE.
• GENETIC POLYMORPHISM CAN CAUSE RESISTANCE – CYP2C19
• THE USUAL DOSE IS 75 MG/DAY. LOADING DOSE MAY BE GIVEN
• THE COMBINATION OF CLOPIDOGREL PLUS ASPIRIN IS SUPERIOR TO ASPIRIN ALONE (TWO DRUGS ARE SYNERGISTIC)
PRASUGREL
• THIS ALSO IS A PRODRUG THAT REQUIRES METABOLIC ACTIVATION.
• HOWEVER, ITS ONSET OF ACTION IS MORE RAPID THAN THAT OF TICLOPIDINE OR CLOPIDOGREL.
• IT PRODUCES GREATER AND MORE PREDICTABLE INHIBITION OF ADP-INDUCED PLATELET AGGREGATION.
• RISK OF BLEEDING IS MORE AND CONTRAINDICATED IN PATIENTS WITH H/O CVA
GLYCOPROTEIN IIB/IIIA INHIBITORS
• GLYCOPROTEIN IIB/IIIA IS A PLATELET-SURFACE INTEGRIN.
• ABCIXIMAB, EPTIFIBATIDE, TIROFIBAN
ABCIXIMAB• IT IS IS THE FAB FRAGMENT OF A HUMANIZED
MONOCLONAL ANTIBODY DIRECTED AGAINST THE ΑIIB Β3 RECEPTOR.
• IT ALSO BINDS TO THE VITRONECTIN RECEPTOR (FACILITATES ADHESION) ON PLATELETS, VASCULAR ENDOTHELIAL CELLS, AND SMOOTH MUSCLE CELLS.
• PATIENTS UNDERGOING PERCUTANEOUS ANGIOPLASTY FOR CORONARY THROMBOSIS —
• TO PREVENT RESTENOSIS, RECURRENT MYOCARDIAL INFARCTION, AND DEATH (IN CONJUNCTION WITH ASPIRIN AND HEPARIN)
DIPYRIDAMOLEMOA
INCREASES CAMP LEVEL BY INHIBITING CYCLIC NUCLEOTIDE PHOSPHODIESTERASES ( INVOLVED IN METABOLISM OF CAMP)
DIPYRIDAMOLE IS A POTENT CORONARY VASODILATOR
NEWER ANTIPLATELET AGENTS
• CANGRELOR AND TICAGRELOR : DIRECT-ACTING REVERSIBLE P2Y12ANTAGONISTS.
THROMBIN RECEPTOR ANTAGONISTS• VORAPAXAR (SCH530348 ) AND
ATOPAXAR (E5555)
USE OF ANTIPLATELETS
•ACUTE CORONARY SYNDROME•CORONARY ARTERY DISEASE•CEREBRO VASSCULAR DISEASE• PROSTHETIC HEART VALVE• PERIPHERAL VASCULAR DISEASE
FIBRINOLYTIC DRUGS
Stable Angina
Acute Coronary Syndrome
Unstable Angina
NSTEMI
STEMI
Not relieved by nitrate Cardiac markers
+VeST Elevation = -Ve
Cardiac markers + Ve
ST Elevation = + Ve
Cardiac markers - Ve
ST Elevation = -Ve
FIBRINOLYSIS
Plasminogen activator inhibitors -1 and -2
Alpha 2-antiplasmin
FIBRINOLYTICS1. STREPTOKINASE.2. ANISTREPLASE.3. UROKINASE4. TISSUE PLASMINOGEN ACTIVATORS –• ALTEPLASE,• RETEPLASE,• TENECTEPLASE
ADVANTAGE OF ALTEPLASE OVER STREPTOKINASE• SPECIFICITY IS MORE – FIBRIN BOUND
PLASMINOGEN• LESS ANTIGENIC
ADVANTAGE OF TENECTEPLASE OVER ALTEPLASE
• LONGER HALF-LIFE –GIVEN AS BOLUS DOSE• RESISTANT TO PAI-1 INHIBITION
COMPARISON
USE OF FIBRINOLYTIC
•STEMI• ISCHAEMIC STROKE (ALTEPLASE)•PULMONARY EMBOLISM•DEEP VEIN THROMBOSIS
INHIBITORS OF FIBRINOLYSIS
• COMPETES FOR LYSINE BINDING SITES ON PLASMINOGEN AND PLASMIN, BLOCKING THE INTERACTION OF PLASMIN WITH FIBRIN.• AMINOCAPROIC ACID• TRANEXAMIC ACID
THANK YOU