Platelets usually circulate in plasma in an inactive form, but following injury to blood vessels they become activated and adhere to site of injury. Platelet aggregation then occurs, which contributes to haemostatic plug. Platelet aggregation involves binding of fibrinogen with a glycoprotein IIb/IIIa receptor on platelet surface. The activated platelets secrete substances such as adenosine diphosphate (ADP) and thromboxane A2 that result in additional platelet aggregation and also cause vasoconstriction. Finally a number of platelet derived factors stimulate production of thrombin and hence fibrin through coagulation cascade (see The blood clotting process, ). Opposing this process is fibrinolysis pathway, which is initiated during clot formation by a number of mediators such as tissue plasminogen activator (tPA) and urokinase. These proteins convert plasminogen to plasmin, which in turn degrades fibrin, main component of clot.
Antiplatelet drugs (see table 1 below,(below)) reduce platelet aggregation and are used to prevent thromboembolic events. They act through a wide range of mechanisms including:
prevention of thromboxane A2 synthesis or inhibition of thromboxane receptors e.g. aspirin inhibits platelet cyclo-oxygenase,preventing synthesis of thromboxane A2
• interference in final step in platelet aggregation by stopping fibrinogen binding with glycoprotein IIb/IIIa receptor on platelet surface
Therefore some antiplatelet drugs can have beneficial additive effects with other antiplatelet drugs that act via different mechanisms. Furthermore,other drugs such as dextrans, heparin, some prostaglandins and sulfinpyrazone also have some antiplatelet activity.
Thrombolytics (see table 1 below, (below)) are used in treatment of thromboembolic disorders. Thrombolytics activate plasminogen to form plasmin, which is a proteolytic enzyme that degrades fibrin and therefore produces clot dissolution.
This section is primarily concerned with those interactions where activities of antiplatelet drugs or thrombolytics are changed by presence of another drug. Note that interactions of high-dose aspirin are covered under analgesics
Cilostazol,Dipyridamole
Aspirin,Indobufen, Triflusal
Abciximab,Eptifibatide, Tirofiban
Clopidogrel,Ticlopidine
Ditazole,Trapidil
Alteplase,Anistreplase, Defibrotide, Reteplase, Streptokinase, Tenecteplase, Urokinase
| Table 1 Antiplatelet drugs and thrombolytics | |
|---|---|
| Group | Drugs |
| Antiplatelet drugs | |
| Adenosine reuptake inhibitors/Phosphodiesterase inhibitors | Cilostazol, Dipyridamole |
| Cyclo-oxygenase inhibitors | Aspirin, Indobufen, Triflusal |
| Glycoprotein IIb/IIIa-receptor antagonists | Abciximab, Eptifibatide, Tirofiban |
| Thienopyridines (inhibitors of adenosine diphosphate mediated platelet aggregation) | Clopidogrel, Ticlopidine |
| Thromboxane receptor antagonists | Picotamide |
| Miscellaneous | Ditazole, Trapidil |
| Thrombolytics | |
| Thrombolytics | Alteplase, Anistreplase, Defibrotide, Reteplase, Streptokinase, Tenecteplase, Urokinase |
| Table 2 Antiplatelet drugs and thrombolytics | |
|---|---|
| Group | Drugs |
| Antiplatelet drugs | |
| Adenosine reuptake inhibitors/Phosphodiesterase inhibitors | Cilostazol, Dipyridamole |
| Cyclo-oxygenase inhibitors | Aspirin, Indobufen, Triflusal |
| Glycoprotein IIb/IIIa-receptor antagonists | Abciximab, Eptifibatide, Tirofiban |
| Thienopyridines (inhibitors of adenosine diphosphate mediated platelet aggregation) | Clopidogrel, Ticlopidine |
| Thromboxane receptor antagonists | Picotamide |
| Miscellaneous | Ditazole, Trapidil |
| Thrombolytics | |
| Thrombolytics | Alteplase, Anistreplase, Defibrotide, Reteplase, Streptokinase, Tenecteplase, Urokinase |