Lievykh A. Comparative analysis of anti- and proaggregatory properties of NSAIDs depending on their anticyclooxygenase selectivity

The dissertation is devoted to experimental solution of the problem of rational use of nonsteroidal anti-inflammatory drugs (NSAIDs) depending on their anticyclooxygenase selectivity and influence on platelet aggregation. It has been ascertained that different NSAIDs render both stimulatory and inhibitory influence on platelets functional activity. Proaggregatory properties were shown not to be class-specific effect of COX-2 selective drugs. Combined administration of rofecoxib together with antiaggregants allows to reduce negative proaggregatory influence of this NSAID. It has been shown that the combined drug of acetylsalicylic acid (ASA) and thiotriazolin is more effective and safe in comparison to ASA alone that appears in intensifying of antiaggregative action and reduction of negative influence on stomach mucosa. Mechanism of antiaggregative action of this combined drug, besides irreversible inhibition of platelet COX, is connected with reduction of oxidative stress, stabilization of platelets membranes and reduction of arachidonic acid release from them, activation of platelet NO-synthase, nitric oxide level increase, and also inhibition of thromboxane А2 production.