Voloshchuk N. Sex factors in the formation of pharmacological activity and toxicity of modern nonsteroidal anti-inflammatory drugs

Dissertation is devoted to the problem of improvement of efficiency and safety of nonsteroidal anti-inflammatory drugs therapy at male and female on the basis of research of pharmacokinetic and metabolic mechanisms which provide formation of sex differences in the answer of an organism to the action of NSAIDs and a substantiation of approaches to the correction of gastro - and nephrotoxicity of these preparations. The basic contribution to the formation of gender differences in specific activity and toxicity of NSAIDs bring type of sex hormones and individual level of their production. More expressed analgesic and anti-inflammatory effects and lower toxicity is associated with estrogens, while high toxicity and less expressed therapeutic effect - with testosterone. Female prevalence in specific pharmacological activity of NSAIDs is caused by slow elimination of these drugs from the organism that is connected with smaller activity of enzymes which provide biotransformation of NSAIDs. At the same time, higher toxicity of these drugs in males is interfaced to smaller resistibility of a stomach mucous membrane and kidneys to the damaging factors, and also higher ability of diclophenac to reduce Н2S-stimulated vasodilatation of mesenteric and renal arteries in males.