Metabolic alteration of drugs

Most drugs are not excreted unchanged by the kidneys but first are biotransformed to metabolites that then are excreted. Renal failure not only may retard the excretion of these metabolites, which in some cases have important pharmacologic activity, but, in some cases, alters the nonrenal as well as the renal metabolic clearance of drugs (15, 24). The impact of impaired renal function on drug metabolism is dependent on the metabolic pathway, as indicated in Table 5.2. In most... 

Taken together, FXR not only regulates bile acid homeostasis but also greatly impacts on transporters and enzymes involved in drug metabolism. Effects on phase I—III genes by bile acid-activated FXR may therefore at least in part explain alterations of drug metabolism in cholestatic liver disease [62, 85, 86]. 

X.S. Teefore. Mr. Teefore could be treated with antithyroid drugs, by ) subtotal resection of the thyroid gland, or with radioactive iodine. Suc- cessful treatment normalizes thyroid hormone secretion, and all of the signs, symptoms, and metabolic alterations of hyperthyroidism quickly subside. 

However, how these metabolic changes lead to the reduced life span of the red cells is unclear. The drugs do not accelerate hemolysis in vitro, and therefore it has been suggested that the metabolic alteration of the red cell makes it more detectable or more sensitive to the lytic action of the reticuloendothelial cells. 

In recent years, the intestinal mlcroflora has been recognized as a site of drug metabolism. Schellne has studied the metabolism of a number of drugs in rat caecal mlcroflora and found extensive metabolic alteration of these compounds. 

Disorders of lipoprotein metabolism involve perturbations which cause elevation of triglycerides and/or cholesterol, reduction of HDL-C, or alteration of properties of lipoproteins, such as their size or composition. These perturbations can be genetic (primary) or occur as a result of other diseases, conditions, or drugs (secondary). Some of the most important secondary disorders include hypothyroidism, diabetes mellitus, renal disease, and alcohol use. Hypothyroidism causes elevated LDL-C levels due primarily to downregulation of the LDL receptor. Insulin-resistance and type 2 diabetes mellitus result in impaired capacity to catabolize chylomicrons and VLDL, as well as excess hepatic triglyceride and VLDL production. Chronic kidney disease, including but not limited to end-stage... 

Their activities may be altered in diseased tissues (eg, cirrhosis), affecting drug metabolism Genotyping the P450 profile of patients (eg, to detect polymorphisms) may in the future permit individualization of drug therapy... 

White JF, Carlson GP. 1979. Influence of alterations in drug metabolism on spontaneous and epinephrine-induced cardiac arrhythmias in animals exposed to trichloroethylene. Toxicol Appl Pharmacol 47 515-527. 

While generally not of major concern, omeprazole may inhibit the metabolism of warfarin, diazepam, and phenytoin lansoprazole may decrease theophylline concentrations. Drug interactions with omeprazole are of particular concern in patients who are considered slow metabolizers, as are approximately 3% of the Caucasian population. Unfortunately, it is unclear which patients have the polymorphic gene variation that makes them slow metabolizers.17 The metabolism of esomeprazole may also be altered in patients with this polymorphic gene variation. Patients on potentially interacting drugs should be monitored for development of drug-related problems. 

Drugs can affect thyroid function in a number of ways.41 Effects of drugs on thyroid hormone protein binding, LT4 absorption, and metabolism have been discussed previously. Several commonly used medications can alter thyroid hormone secretion. 

Drug molecules may be chemically or metabolically altered at various sites along the GIT including within gut fluids, within the gut wall, and by microorganisms present in the low end of the tract. These sites are noted in Fig. 18. Several examples of enzymatic... 

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