Antiplatelet anticoagulant fibrinolytics.pptx

Pharmacology of antiplatelets, anticoagulants, fibrinolytics, nitrates

1. P harmacology of Antiplatelets, Anticoagulants, Fibrinolytics & Nitrates

2. Antiplatelet (Aspirin) Irreversibly inhibiting the cyclooxygenase enzyme (COX) activity in the prostaglandin synthesis pathway (PGH2) Prostaglandin Precursor of thromboxane A2 and prostacyclin (PGI2) TXA2 Inducing platelet aggregation & vasoconstriction COX-1 mediates its production PGI2 Inhibiting platelet aggregation and induces vasodilatation Mediated b y COX-2

3. Low-dose aspirin (75 mg to 150 mg) can induce complete or near-complete inhibition of COX-1  inhibiting the production of TXA2 Larger doses are required to inhibit COX-2

4. Selectively inhibit ADP-induced platelet aggregation Antiplatelet (P2Y12 Receptor Antagonists) P2Y12 Chemoreceptor for ADP (adenosine diphosphate) Examples: Clopidogrel Prasugrel Ticagrelor

5. Only available in IV form Antiplatelet (GP IIb/IIIa Receptor Inhibitors) GP IIb/ IIIa receptor for platelet aggregation with each other & with fibrinogen and vWF

6. PDE3A hydrolyzes cAMP to 5' AMP P hosphodiesterases (PDEs) regulate the level of cAMP, ( major inhibitor of platelet activation pathways) The inhibition of PDEs may therefore exert a strong platelet inhibitory effect Antiplatelet (Phosphodiesterase Inhibitors)

7. Coagulation Cascade Consists of three pathways Extrinsic Intrinsic Common pathway Intrinsic pathway spontaneous, internal damage of the vascular endothelium Extrinsic pathway activated secondary to external trauma Both intrinsic and extrinsic pathways meet at a shared point to continue coagulation - the common pathway.

8. Derive their effect by acting at different sites of the coagulation cascade. 02 Medicines that prevent blood clots from forming in the bloodstream. 01 Anticoagulant Some act directly by enzyme inhibition Some indirectly, by binding to antithrombin or by preventing their synthesis from the liver (vitamin K dependent factors).

9. Available Anticoagulants Low Molecular Weight Heparin (LMWH) Unfractionated Heparin (UFH) Vitamin K Dependent Antagonists (VKA) Direct Thrombin Inhibitors Direct Factor 10a Inhibitors

10. Unfractionated Heparin (UFH) Onset of action is rapid, has a short half-life M ake complexes with antithrombin 3 (synthesized in the liver), and inactivates various clotting factors (thrombin, factors IX, X, XI and XII) Can be monitored using activated partial thromboplastin ( aPTT ), The recommended target ratio of aPTT is 1.5 to 2.2 times the patients' aPTT .

11. Low Molecular Weight Heparin (LMWH) ( enoxaparin, dalteparin , tinzaparin, nadroparin) longer length of action, long half-life Derived from heparin by chemical/enzymatic degradatiom LMWH-antithrombin 3 complex only inhibits factor Xa Hemorrhage is more problematic because of longer half life and relative irreversibility

12. Vitamin K Dependent Antagonists (VKA) (Warfarin) Vit K converted back to its reduced form by Vit K reductase, to activate more clotting factors Clotting factors II, VII, IX and X are activated by Vit K  Vit K is then oxidised in the process Warfarin similar structure to Vit K  competitively inhibits Vit K reductase Requires monitoring of INR and regular dose adjustments (increase risk of hemorrhage when INR elevated above therapeutic level)

13. Direct Thrombin Inhibitors Inhibit the cleavage of fibrinogen to fibrin by thrombin Bivalirudin Argatroban Dabigatran. All products are renally metabolized

14. Direct Factor Xa Inhibitors Inhibition of the cleavage of prothrombin to thrombin by binding directly to Factor Xa Rivaroxaban Apixaban Edoxaban Betrixaban Only orally administered

15. Fibrinolytics (Thrombolytics) Plasmin lyses fibrin  dissolves thrombi Activates plasminogen to plasmin

16. Urokinase 3 Fibrinolytics (Thrombolytics) Tissue Plasminogen Activators (tPA) 1 Streptokinase 2

17. Contraindications of Fibrinolytic Therapy 3 4 1 2 3 4 1 2

18. Nitrates D erived from nitroglycerin A ct as both venodilators and arteriodilators Venodilator R educed cardiac output and oxygen demand (preload) Arteriodilator Reduces afterload

19. Nitrates Isosorbide dinitrate Isosorbide mononitrate GTN