Renal disease effects

Vergne-Marini P, Parker TF, Pak CY, Hull AR, DeLuca he and Fordtran JS (1976) fqunal and ileal absorption in patients with chronic renal disease. Effect of lalpha-hydroxycholecalciferol. J Clin Invest 57 861-866. 

In the treatment of hypertension, ACE inhibitors are as effective as diuretics, (3-adrenoceptor antagonists, or calcium channel blockers in lowering blood pressure. However, increased survival rates have only been demonstrated for diuretics and (3-adrenoceptor antagonists. ACE inhibitors are approved for monotherapy as well as for combinational regimes. ACE inhibitors are the dtugs of choice for the treatment of hypertension with renal diseases, particularly diabetic nephropathy, because they prevent the progression of renal failure and improve proteinuria more efficiently than the other diugs. 

Erythropoietin (Eprex ) is physiologically produced in the kidney and regulates proliferation of committed progenitors of red blood cells. It is used to substitute erythropoietin in severe anemias due to end stage renal disease or treatment of cancer with cytostatic agents. Side effects include hypertension and increased risk of thrombosis. 

Insulin resistance occurs when the normal response to a given amount of insulin is reduced. Resistance of liver to the effects of insulin results in inadequate suppression of hepatic glucose production insulin resistance of skeletal muscle reduces the amount of glucose taken out of the circulation into skeletal muscle for storage and insulin resistance of adipose tissue results in impaired suppression of lipolysis and increased levels of free fatty acids. Therefore, insulin resistance is associated with a cluster of metabolic abnormalities including elevated blood glucose levels, abnormal blood lipid profile (dyslipidemia), hypertension, and increased expression of inflammatory markers (inflammation). Insulin resistance and this cluster of metabolic abnormalities is strongly associated with obesity, predominantly abdominal (visceral) obesity, and physical inactivity and increased risk for type 2 diabetes, cardiovascular and renal disease, as well as some forms of cancer. In addition to obesity, other situations in which insulin resistance occurs includes... 

Loop diuretics are used in the treatment of edema associated with CHF, cirrhosis of the liver, and renal disease, including the nephrotic syndrome. These drug s are particularly useful when a greater diuretic effect is desired. Furosemide is the drug of choice when a rapid diuresis is needed or if the patient has renal insufficiency. Furosemide and torsemide are also used to treat hypertension. Ethacrynic acid is also used for the short-term management of ascites caused by a malignancy, idiopathic edema, or lymphedema. 

RANicH T, BHATHENA s J and VELASQUEZ M T (2001) Protective effects of dietary ph)doestrogens in chronic renal disease. J Ren Nutr. 11 (4) 183-93. 

Once the loading dose of the AED is administered, it is important to remember to initiate maintenance doses to ensure that therapeutic levels are sustained. Chronic and idiosyncratic side effects as well as potential drug interactions should be considered if the patient will continue AED therapy indefinitely. All drug therapy should be adjusted for any hepatic or renal disease states. Table 28-1 summarizes the drug doses used in SE, and Table 28-2 provides an example of an algorithm for the treatment of patients in SE. Published studies comparing these treatment strategies are summarized in Table 28-3. 

Thiazide diuretics such as chlorothiazide act on the distal tubule, a portion of the tubule that is permeable to sodium. The mechanism of action of these diuretics involves inhibition of NaCl reabsorption by blocking the Na+, CL symporter in the luminal membrane. The thiazide diuretics are only moderately effective due to the location of their site of action. Approximately 90% of the filtered Na+ ions have already been reabsorbed when the filtrate reaches the distal tubule. These drugs may be used for treatment of edema associated with heart, liver, and renal disease. Thiazide diuretics are also widely used for the treatment of hypertension. 

TABLE 77-1 Effect of End-Stage Renal Disease on Nonrenal Clearance of Selected Drugs ... 

Many laboratory animal models have been used to describe the toxicity and pharmacology of chloroform. By far, the most commonly used laboratory animal species are the rat and mouse models. Generally, the pharmacokinetic and toxicokinetic data gathered from rats and mice compare favorably with the limited information available from human studies. PBPK models have been developed using pharmacokinetic and toxicokinetic data for use in risk assessment work for the human. The models are discussed in depth in Section 2.3.5. As mentioned previously, male mice have a sex-related tendency to develop severe renal disease when exposed to chloroform, particularly by the inhalation and oral exposure routes. This effect appears to be species-related as well, since experiments in rabbits and guinea pigs found no sex-related differences in renal toxicity. 

Studies indicate that renal effects may be specific to certain strains of male rats that synthesize ttzu-globulin. Monkeys, guinea pigs, dogs, mice, female rats, and male NBR rats that do not synthesize the hepatic form of a u-globulin do not develop renal disease in response to isophorone. 

Metabolic acidosis In severe renal disease uncontrolled diabetes circulatory insufficiency due to shock, anoxia, or severe dehydration extracorporeal circulation of blood cardiac arrest and severe primary lactic acidosis where a rapid increase in plasma total CO2 content is crucial. Treat metabolic acidosis in addition to measures designed to control the cause of the acidosis. Because an appreciable time interval may elapse before all ancillary effects occur, bicarbonate therapy is indicated to minimize risks inherent to acidosis itself. 

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