Kidney disease states affecting

The kidney is an organ that performs several important functions essential to sustain life. These functions include the regulation of volume and electrolyte homeostasis, control of acid-base balance, and the excretion of waste products. The kidney also has endocrine functions including renin secretion, stimulation of erythropoietin formation, and activation of vitamin D. Numerous disease states (e.g., infections, shock, diabetes, gout) can affect the ability of the kidney to perform its normal functions, and if these diseases are not properly treated, serious illness or death can result. 

In summary, it is clear that massive amounts of traditional NSAIDs and COX-2 specific inhibitors will continue to be consumed worldwide. Because these agents inhibit renal prostaglandin synthesis, they affect salt and water homeostasis and renal hemodynamics. This inhibition will have little clinical effect in the majority of patients who are well-hydrated, have good renal function, and no concomitant disease states. However, both traditional NSAIDs and COX-2 specific inhibitors must be used judiciously in patients with compromised renal blood flow. In general, the COX-2 specific inhibitors are well tolerated by the kidney and it is only in the clinical setting of significant pre-existing renal im-... 

Many disease states can cause individual variation in response to drugs. Any disease that results in alteration in the pharmacokinetics of a drug will create these variations. Diseases of the liver and kidney, any disease that affects intestinal motility, mal-absorption syndromes and any condition that reduces plasma protein concentration are all implicated. Some diseases can alter the physiological sensitivity to a drug at its site of action. 

A number of processes occur in the kidney which affect the rate of drug excretion. The most important processes are glomerular filtration, tubular secretion and tubular reabsorption. These processes are compared in Table 1.3. Drug excretion mechanisms are vulnerable to renal insults such as toxins, other drugs, or disease states. Because drugs, metabolites and toxins are concentrated in the kidney, the organ is frequently the site of chemical-induced toxicity. Undesirable symptoms in a patient with renal failure may be due to drug accumulation rather than the disease process itself. 

Tocainide is rapidly and well absorbed from the GI tract and undergoes very fitde hepatic first-pass metabolism. Unlike lidocaine which is - 30% bioavailable, tocainide s availability approaches 100% of the administered dose. Eood delays absorption and decreases plasma levels but does not affect bio availability. Less than 10% of the dmg is bound to plasma proteins. Therapeutic plasma concentrations are 3—9 jig/mL. Toxic plasma levels are >10 fig/mL. Peak plasma concentrations are achieved in 0.5—2 h. About 30—40% of tocainide is metabolized in the fiver by deamination and glucuronidation to inactive metabolites. The metabolism is stereoselective and the steady-state plasma concentration of the (3)-(—) enantiomer is about four times that of the (R)-(+) enantiomer. About 50% of the tocainide dose is efirninated by the kidneys unchanged, and the rest is efirninated as metabolites. The elimination half-life of tocainide is about 15 h, and is prolonged in patients with renal disease (1,2,23). 

Similarly the state of health of a person can affect the way they handle a drug or other chemical substance by altering, for example, their metabolic capability or kidney function. Serious diseases affecting the function of a particular organ will have major effects if that organ is involved in the metabolism or excretion of the drug. 

The serum concentration of Pi increases with a physiological dechne in renal function associated with aging (but not renal disease per se). Healthy individuals excrete approximately 67% of their absorbed phosphate via the urine and the remainder via the gut as endogenous secretions. As the glomerular filtration capacity of the kidneys declines, the serum Pi concentration increases and more Pi is retained by the body. PTH secretions increase but the typical serum PTH concentrations, although elevated, remain within the upper limits of the normal range, at least for a decade or so. Thereafter, however, serum Pi and PTH both continue to climb as renal function declines and increased rates of bone turnover lead to measurable bone loss. This situation probably affects millions in the United States each year as they enter the 50s and proceed into the 60s many of these individuals are overweight or obese and have the metabolic syndrome, which... 

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