Inhibitors pathophysiology

Cyclosporine and tacrolimus are calcineurin inhibitors that are administered as part of immunosuppressive regimens in kidney, liver, heart, lung, and bone marrow transplant recipients. In addition, they are used in autoimmune disorders such as psoriasis and multiple sclerosis. The pathophysiologic mechanism for ARF is renal vascular vasoconstriction.41 It often occurs within the first 6 to 12 months of treatment, and can be reversible with dose reduction or drug discontinuation. Risk factors include high dose, elevated trough blood concentrations, increased age, and concomitant therapy with other nephrotoxic drugs.41 Cyclosporine and tacrolimus are extensively metabolized by... 

CAI, carbonic anhydrase inhibitor. (From LesarTS, Fiscella RG, Edward D. Glaucoma. In DiPiro JT, Talbert RL, Yee GC, et al, (eds.) Pharmacotherapy A Pathophysiologic Approach. 6th ed. 

Despite a long-time studying of superoxide production by mitochondria, an important question is still debated does mitochondria produce superoxide under physiological conditions or superoxide release is always a characteristic of some pathophysiological disorders resulting in the damage of normal mitochondrial functions Uncertainties in this question arise due to the different results obtained with the use of respiratory inhibitors and different analytical methods. 

The application of flavonoids for the treatment of various diseases associated with free radical overproduction is considered in Chapter 29. However, it seems useful to discuss here some studies describing the activity of flavonoids under certain pathophysiological conditions. Oral pretreatment with rutin of rats, in which gastric lesions were induced by the administration of 100% ethanol, resulted in the reduction of the area of gastric lesions [157]. Rutin was found to be an effective inhibitor of TBAR products in the gastric mucosa induced by 50%i ethanol [158]. Rutin and quercetin were active in the reduction of azoxymethanol-induced colonic neoplasma and focal area of dysplasia in the mice [159], Chemopreventive effects of quercetin and rutin were also shown in normal and azoxymethane-treated mouse colon [160]. Flavonoids exhibited radioprotective effect on 7-ray irradiated mice [161], which was correlated with their antioxidative activity. Dietary flavones and flavonols protected against the toxicity of the environmental contaminant dioxin [162], Rutin inhibited ovariectomy-induced osteopenia in rats [163],... 

Beneke S, Diefenbach J, Burkle A (2004) Poly(ADP-ribosyl)ation inhibitors promising drug candidates for a wide variety of pathophysiologic conditions. Int J Cancer 111 813-818... 

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