Antiplatelet drugs, Antithrombotic drugs

1. ANTIPLATELET DRUGS
{ANTITHROMBOTIC
DRUGS}
1. MRS. PRADNYA JAGTAP
2. MS. GARGI TAMBOLI
3. MS. PRAJKTA JAGTAP

2. INTRODUCTION
• THE DRUGS WHICH INTERACT WITH
PLATELET FUNCTIONS ARE KNOWN AS
*ANTIPLATLET DRUGS/ ANTITHROMBOTIC
DRUGS*
• USEFUL IN- PROPHYLAXIS OF
THROMBOEMBOLIC DISORDERS.
• [ EMBOLUS: BLOOD CLOT THAT TRAVELS
THROUGH BLOOD STREAM AND BLOCKS
ARTERY].

3. PLATELET AGGREGATION
• PLATELETS EXPRESS GLYCOPROTEIN [GP] INTEGRIN RECEPTORS ON SURFACES.
• COLLAGEN FIBRES ARE EXPOSED DURING VASCULAR ENDOTHELIUM DAMAGES (EG:
INJURY).
• COLLAGEN REACT WITH GP1A + GP1B RECEPTORS  PLATELET ACTIVATION  RELEASE
OF TXA2(THROMBOXANE A2), ADP(ADENOSINE DI PHOSPHATE) & 5-HT(5-
HYDROXYTRYPTOPHAN) -{VASOCONSTRICTORS}.
• CONFIRMATIONAL CHANGES GP2B/3A RECEP BINDING OF FIBRINOGEN & VON
WILLEBRAND FACTOR[BLOOD GLYCOPROTEIN INVOLVED IN HEMOSTASIS] CROSS
LINKAGE OF PLATELETS(AGGREAGTION AND ANCHORAGE TO VESSEL SURFACE)
PLATELET PLUG FORMS
• PROSTACYCLIN – INHIBITORS OF PLATELET AGGREGATION & THROMBOXANE A2-
INCREASES PLATELET AGGREGATION.
• A BALANCE BET THESE 2 CONTROLS INTRAVASCULAR THROMBUS FORMATION

4. PLATELET AGGREGATION

5. CLASSIFICATION
P2 Y12
RECEPTOR
BLOCKERS

6. ASPIRIN
• IT IS COX1(CYCLOOXYGENASE) AND TXA2 (THROMBOXANE A2) SYNTHESIS INHIBITOR.
• MOA:
• ASPIRIN INHIBITS COX1 AND TXA2 SYNTHASE INACTIVATING THEM IRREVERSIBLY.
• TXA2- ACID PRODUCT GENERATED BY PLATELET.
• PLATELETS ARE EXPOSED TO ASPIRIN IN PORTAL CIRCULATION BEFORE DEACETYLATION OF
ASPIRIN IN LIVER.
• AT LOW DOSES TXA2 FORMATION IS SUPPRESSED THUS FRESH ENZYME SYNTHESIS
TAKES TIME.
• PROLONGATION OF BLEEDING TIME LASTS 5-7 DAYS.
• CUMULATIVE EFFECT- 40 MG/ DAY ,MAX- 75-150 MG / DAY.
• IN VESSEL WALLS- INHIBITION OF COX1  DECREASED PGI2 SYSYNTHESIS (HOWEVER FRESH
ENZYMES ARE SYNTHESIZED).
• AT LOW DOSES 75- 150 MG/ DAY SELECTIVELY TXA2 IS SUPPRESSED BUT AT HIGHER DOSES
BOTH TXA2 AND PGI2 ARE SUPPRESSED.

7. ASPIRIN
• USES:
• IN CORONARY ARTERY
DISEASES --- PREVENTION OF
MYOCARDIAL INFARCTION
• PREVENTION OF ISCHEMIC
EVENTS IN PATIENTS WITH
ANGINA PECTORIS.
MOA

8. DIPYRIDAMOLE
• VASODILATOR USED IN ANGINA PECTORIS.
• MOA:
• INHIBITS PHOSPHPDIESTERASE ENZYME AS WELL AS INHIBIT
UPTAKE OF ADENOSINE IN PLATELET TO INCREASE CAMP WHICH
POTENTIATES PGI2 AND INTERFERE WITH AGGREGATION.
• LEVELS OF TXA2 AND PGI2 ARE NOT ALTERED.
• HALF LIFE- 10-12 HRS
• ENHANCES ANTIPLATLET ACTION OF ASPIRIN.

9. DIPYRIDAMOLE
• USES:
• USED TO PREVENT
THROMBOEMBOLISM IN PATIENTS
WITH PROSTHETIC HEART VALVES
(ARTIFICIAL HEART VALVE).
• LOWERS THE RISK OF STROKE IN
PATIENTS WITH TRANSIENT
ISCHAEMIC ATTACKS( STROKE
ATTACK).
MOA

10. P2Y12 RECEP. BLOCKERS { ADP
ANTAGONIST}
• P2Y12 RECEPTORS THESE
RECEPTORS ARE THE
CHEMORECEPTORS FOR ADP.
• THE MAIN DRUGS INCLUDED
IN THIS CLASS ARE AS
FOLLOWS:
1. TICLODIPINE
2. CLOPIDOGREL
3. PRASUGREL
Act by inhibition of ADP

11. TICLODIPINE
• IT IS A THIENOPYRIDINE DERIVATIVE.
• IT IS 1ST DRUG TO ALTER SYRFACE RECEPETORS ON PLATELETS AND INHIBITS
ADP & FIBRINOGEN INDUCED PLATELET AGGREGATION.
• MOA:
• GI COUPLED P2Y12 RECEPTORS MEDIATES ADP INDUCED ADENYLYL CYCLASE
INHIBITION BLOCKED IRREVERSIBLY PLATELET ACTIVATION INTERFERED.
• PREVENTS BINDING OF FIBRINOGEN TO PLATELETS BUT DOES NOT
INTERFERE GP2B/3A RECEP.
• TXA2 IS ALSO NOT AFFECTED  BUT BLEEDING TIME IS PROLONGED
PLATELETS SURVIVAL IN EXTRA –CORPOREAL CIRCULATION IS INCREASED.
• IT ALSO SHOWS SYNERGISTIC ACTION WHEN GIVEN WITH ASPIRIN.

12. TICLODIPINE
• KINETICS:
• ORALLY ABSORBED
• COVERTS TO ACTIVE METABOLITE IN
BODY.
• HALF LIFE-8 HRS , CUMULATIVE
EFFECT-8-10 DAYS
• USES:
1. PROPHYLAXIS OF MYOCARDIAL
INFARCTION
2. USED IN UNSTABLE ANGINA

13. PRASUGREL
• IT IS A PRODRUG.
• THIS IS THE LATEST, MOST POTENT AND
FASTER ACTING P2Y12 PURINERGIC RECEPTOR
BLOCKER.
• IT IS BEING INCREASINGLY USED IN ACUTE
CORONARY SYNDROMES (ACS).
• ALSO USED WHEN STRONG ANTIPLATELET
ACTION IS REQUIRED.

14. GP 2B/3AANTAGONIST
• THESE ANTAGONIST ACT BY
BLOCKING THE KEY RECEPTOR
INVOLVED IN PLATELET
AGGREGATION.
• GP IIB/IIIAANTAGONISTS BLOCK
AGGREGATION INDUCED BY ALL
PLATELET AGONISTS

15. ABCIXIMAB
• IT IS THE FAB FRAGMENT OF A CHIMERIC MONOCLONAL ANTIBODY
AGAINST GP IIB/IIIA, PROTEIN.
• BUT IS RELATIVELY NONSPECIFIC AND BINDS TO SOME OTHER
SURFACE PROTEINS AS WELL.
• ASPIRIN + HEPARIN DURING PCI REDUCES THE INCIDENCE OF
RESTENOSIS, SUBSEQUENT MI AND DEATH.
• ABCIXIMAB TO CLOPIDOGREL (600 MG ORAL DOSE) FOR PCI IN HIGH-
RISK ACS PATIENTS, REDUCES ISCHAEMIC EVENTS BY 25%.
• BOLUS DOSE, PLATELET AGGREGATION REMAINS INHIBITED FOR 12–
24HR
• T½ : 10–30 MIN.

16. EPTIFIBATIDE
• IT IS A SYNTHETIC CYCLIC PEPTIDE.
• SELECTIVELY BINDS TO PLATELET SURFACE GPIIB/IIIA RECEPTOR  INHIBITS
PLATELET AGGREGATION.
• T½ OFTHE DRUG IS- (2.5 HOURS).
• PLATELET INHIBITION REVERSES IN A SHORTER TIME (WITHIN 6–10 HOURS) BECAUSE
IT QUICKLY DISSOCIATES FROM THE RECEPTOR
• ADVERSE EFFECT-
1. BLEEDING
2. THROMBOCYTOPENIA
• RARE EFFECTS:
1. RASHES
2. ANAPHYLAXIS

17. TIROFIBAN
• IT IS A NONPEPTIDE.
• BUT SPECIFIC GPIIB/IIIA
ANTAGONIST THAT IS SIMILAR
IN PROPERTIES TO
EPTIFIBATIDE.
• T½ IS 2 HOURS.
• THE INDICATIONS AND
ADVERSE EFFECTS ARE ALSO
SIMILAR TO EPTIFIBATIDE.

18. THANK YOU