Editor-in-Chief Hatice Kübra Elçioğlu Vice Editors Levent Kabasakal Esra Tatar Online ISSN 2630-6344 Publisher Marmara University Frequency Bimonthly (Six issues / year) Abbreviation J.Res.Pharm. Former Name Marmara Pharmaceutical Journal
Marmara Pharmaceutical Journal 1995 , Vol 11 , Issue 1 - 2
Recent developments in antithrombotic therapy
Jawed Fareed,Demetra D. Callas,Walter Jeske,Helmut Wolf
Recently, many newer developments in the clinical management of thrombotic and cardiovascular disorders have occured. In particular, newer approaches for the prophylactic and therapeutic management of such disorders as venous thrombosis, stroke, acute myocardial infarction and prevention of post-interventional coronary and reocclusive syndromes have been introduced. These have only been possible due to the understanding of the molecular mechanisms involved in the thrombogenic process which play a pivotal role in the pathology of thrombotic and cardiovascular disorders.

With the increased knowledge of the pathophysiology of thrombogenesis have coma advances in drug treatment possibilities. Advances in biotechnology and separation techniques have contributed to the development of many newer antithrombotic, anticoagulant and thrombolytic drugs. Many new drugs and devices based on newer concepts are currently being tested in various clinical trials. Hirudin, hirulog, synthetic and recombinant GpIIb/IIIa targeting drugs and tissue factor pathway inhibitor (TFPI), are some examples.

From these current developments, it can be appreciated that antithrombotic drugs represent a wide spectrum of natural, synthetic, semisynthetic and biotechnology produced agents with marked differences in chemical composition, physicochemical properties, biochemical actions and pharmacologic effects. The use of physical means to treat thrombotic disorders and advanced means of drug delivery add to the expanding nature of treatment.

Besides the development of new antithrombotic and anticoagulant drugs, a better understanding of the conventional anticoagulant and antithrombotics drugs such as heparin, warfarin and aspirin has led to the newer applications for theses drugs. Furthermore,prophylactic and treatment protocols are now optimized using these conventional drugs. A renowned interest is clearly seen to develop an optimal approach for these agents.

The endogenous actions of the antithrombotic drugs are quite complex. It is no longer valid to assume that an antithrombotic drug must produce an anticoagulant action in blood as do the classical heparin and oral anticoagulants. Many of these new drugs do not produce any alteration of currently measurable blood clotting parameters, yet they are effective therapeutic agents because of their interactions with the elements of the blood and vasculature. Another perspective is that several of these agents require endogenous transformation to become active products. Therefore, it becomes important to rely on the pharmacodynamic actions of these agents rather than on other in vitro characteristics to assess potency of efficacy. Hematologic and vascular modulation play a key role in the mediation of the antithrombotic actions of these drugs involving red cells, white cells, platelets, endothelial cells and blood proteins. Thus, an optimal antithrombotic drug/approach will include the targeting of all possible sites involved in thrombogenesis. Polytherapeutic approaches utilizing combinations of drugs may turn to be the most effective in the management of thrombotic disorders. A more optimal use of conventional antithrombotic drugs in monotherapeutic and polytherapeutic approaches will expand their use in the management of thrombotic and cardiovascular indications. Keywords :

Marmara University