Anti-platelet drugs

Anti platelet Drugs. Table 1 Pharmacological properties of GP llb/llla inhibitors... 

Arterial thrombi (white thrombi) are formed initially from both platelets and fibrin in medium-sized arteries on the basis of atherosclerosis. These thrombi can lead to symptoms of, among others, myocardial ischemia and myocardial infarction. The treatment is primarily aimed at prevention of thrombus formation with platelet aggregation inhibitors. For the treatment of myocardial infarction thrombolytic agents are used and for secondary prevention both oral anticoagulants and anti-platelet drugs are employed. 

Indometacin potentiates the effect of anti-platelet drugs and anticoagulants (67). 

Sulfinpyrazone, a pyrazolone derivative, is used both as a uricosuric agent and as an anti-platelet drug. It has similar adverse effects to those of phenylbutazone when taken for long term (SEDA-6, 104). In a large number of patients who took the drug for secondary prevention of myocardial infarction (an indication that was not subsequently accepted), the incidence of adverse effects was not high (1). 

Monoclonal antibodies are coming onto the market at an increasing rate. For example, abciximab is an anti-platelet drug, trastuzumab is active against breast cancer, and adali-mumab and inflixamab treat rheumatoid arthritis. The suffix mab is a convenient guide to products in this category. 

Anti platelet drugs (see Table 19.1 , (below)) reduce platelet aggregation and are used to prevent thromboembolic events. They act through a wide range of mechanisms including ... 

Although generally well tolerated, CSFs may cause bone pain in around 25% of patients. This may be managed with acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs), although attention to the platelet count is warranted with the use of NSAIDs. Sargramostim in particular may result... 

Another vasoactive substance produced by the endothelium is thromboxane A2 (TxA2). Normally, small amounts of TxA2 are released continuously however, increased synthesis appears to be associated with some cardiac diseases. Synthesized from arachidonic acid, a plasma membrane phospholipid, TxA2 is a potent vasoconstrictor. Furthermore, this substance stimulates platelet aggregation, suggesting that it plays a role in thrombotic events such as myocardial infarction (heart attack). Nonsteroidal anti-inflammatory drugs such as aspirin and ibuprofen block formation of TxA2 and reduce formation of blood clots. 

Inoue, K., Aoki, Y., Hayashi, M., Kitahara, S., Tanabe, H., Kiyoki, M., and Araki, H., Ex vivo anti-platelet effects of isocarbacyclin methyl ester incorporated in lipid microspheres in rabbits, Arzneim-Forsch/Drug Research, 1995, 45, 980-984. 

A double-blind, placebo-controlled study in which a 4 mg dose of molsidomine was orally administered confirmed the anti-aggregatory effects of the drug when administered intravenously. Although the anti-platelet effects were maintained 1 h after molsidomine administration, bleeding time was unaffected [89]. 

The risk of these events is increased by the use of indwelling epidural catheters for administration of analgesia or by the concomitant use of drugs affecting hemostasis, such as nonsteroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, or other anticoagulants. The risk also appears to be increased by traumatic or repeated epidural or spinal puncture. 

Drug therapy of acute coronary syndromes including unstable angina and non-Q-wave myocardial infarction includes use of aspirin, heparin and anti-ischaemic drugs and is similar in older patients to other age groups. Activation of platelet thromboxane production in the coronary circulation has been demonstrated in unstable angina. The risk of myocardial infarction or death is reduced by approximately 50% by early aspirin therapy in recommended doses of 160-325 mg per day and continued... 

Pathophysiologically, primary haemostatic defects, characteristically due to malfunction of vascular endothelial or platelets, are exemplified by von Willebrand disease and agents such as aspirin and non-steriodal anti-inflammatory drugs (NSAID) where there is a prolonged bleeding time or abnormality in closure using the laboratory equivalent of platelet function analyse the PEA-100. In contrast, secondary bleeding, follows a period of haemostasis... 

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