Renal failure 49

The vitamin D3 metabolite la,25-dihydroxycholecalciferol is a lifesaving drug in treatment of defective bone formation due to renal failure. Retrosynthetic analysis (E.G. Baggjolint, 1982) revealed the obvious precursors shown below, a (2-cyclohexylideneethyl)diphenylphosphine oxide (A) and an octahydro-4f/-inden-4-one (B), to be connected in a Wittig-Homer reaction (cf. section 1.5). 

Elecainide is weU absorbed and 90% of the po dose is bioavailable. Binding to plasma protein is only 40% and peak plasma concentrations are attained in about 1—6 h. Three to five days may be requited to attain steady-state plasma concentrations when multiple doses are used. Therapeutic plasma concentrations are 0.2—1.0 lg/mL. Elecainide has an elimination half-life of 12—27 h, allowing twice a day dosing. The plasma half-life is increased in patients with renal failure or low cardiac outputs. About 70% of the flecainide in plasma is metabolized by the Hver to two principal metaboUtes. The antiarrhythmic potency of the meta-O-dealkylated metaboUte and the meta-O-dealkylated lactam, relative to that of flecainide is 50 and 10%, respectively. The plasma concentrations of the two metaboUtes relative to that of flecainide are 3—25%. Elecainide is mainly excreted by the kidneys, 30% unchanged, the rest as metaboUtes or conjugates about 5% is excreted in the feces (1,2). 

Sotalol is rapidly and almost completely (>90%) absorbed. Bioavahabhity of absorbed dmg is 89—100%. Peak plasma levels are achieved in 2—4 h. Sotalol is 50% bound to plasma proteins. Plasma half-life of the compound is about 5.2 h. No metabolites of sotalol have been identified indicating littie metabolism. The dmg is excreted mainly by the kidneys (80—90%) and about 10% is eliminated in the feces. The plasma half-life is prolonged in patients having renal failure. Kinetics of the compound are not affected by changes in liver function (1,2). Sotalol has ah the adverse effects of -adrenoceptor blockers including myocardial depression, bradycardia, transient hypotension, and proarrhythmic effects (1,2). 

Absorption of nadolol after po dosing is variable, averaging about 30%. The presence of food does not affect absorption. There is no hepatic first-pass metabolism and peak plasma concentrations are achieved in 3—4 h after po doses. About 30% of the plasma concentration is protein bound. The elimination half-hfe of nadolol is 20—24 h, allowing once a day dosing. The dmg is excreted unchanged by the kidneys and its excretion is delayed in patients having renal failure (98,99,108). 

After po doses, atenolol is rapidly but incompletely absorbed ( 50%) from the GI tract, and 50% is excreted unchanged in the feces. Six to 16% of the plasma concentration is bound to protein. Atenolol undergoes Httie first-pass metaboHsm. Peak plasma concentrations occur in 2—4 h after po doses. The elimination half-hfe of atenolol is 6—7 h. Excretion of absorbed dmg is mainly by the kidneys and elimination can be impaired in patients having renal failure. The adverse effects of atenolol are similar to those seen for propranolol therapy (98,99,108). 

The water solubiUty of glutaric acid fosters its toxicity. Glutaric acid is a known nephrotoxin. Renal failure has been documented ia rabbits adruinistered sodium glutarate subcutaneously (124). Dibasic ester (Du Pont), which contains primarily dimethyl glutarate, has low acute toxicity by inhalation and by ingestion, and is moderately toxic via dermal absorption. The acid is both a dermal and ocular irritant of humans. The ester is a severe skin irritant and may cause a rash ia humans (120). 

Diuretics are one of the dmg categories most frequendy prescribed. The principal uses of diuretics are for the treatment of hypertension, congestive heart failure, and mobilization of edema fluid in renal failure, fiver cirrhosis, and ascites. Other applications include the treatment of glaucoma and hypercalcemia, as well as the alkafinization of urine to prevent cystine and uric acid kidney stones. 

Our attention is focus on the biochemical defects of kynurenine pathway. The concentration of metabolites changes under various diseases, such as neurodegenerative disease, memory loss, chronical renal failure, eyes disease. 

Fig.l. The more important metabolites of tryptorhan Degradation of the tryptophan accompanied with increasing in 10 times of kynurenine level in the case of renal failure. As the result of 3-hydroxy-kynurenine s ability of easy oxidize neurotoxin compounds form. 

The most common toxic metals in industrial use are cadmium, chromium, lead, silver, and mercury less commonly used are arsenic, selenium (both metalloids), and barium. Cadmium, a metal commonly used in alloys and myriads of other industrial uses, is fairly mobile in the environment and is responsible for many maladies including renal failure and a degenerative bone disease called "ITA ITA" disease. Chromium, most often found in plating wastes, is also environmentally mobile and is most toxic in the Cr valence state. Lead has been historically used as a component of an antiknock compound in gasoline and, along with chromium (as lead chromate), in paint and pigments. 

Dialysis Concentration gradient < 5 nm Treatment of renal failure... 

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. 

Pentostatin is effective in the treatment of hairy cell leukemia, producing 80-90% remissions (with a complete remission rate of more than 50%). The common side effects of pentostatin include myelosuppression, nausea, and skin rashes. Renal failure,... 

Renal failure Reduced elimination, electrolyte derangements ... 

Inflammatory and immune diseases Autoimmune disease (A,I), asthma (A), osteoarthritis (I), rheumatoid arthritis (I), septic shock (A,I), infections (A,I), familial cold auto-inflammatory syndrome (I), Muckle Wells syndrome (I), chronic infantile neurological cutaneous and articular syndrome/neonatal onset multisystemic inflammatory disease (CINCA/NOMID) (I), Crohn s disease (I), gout (I), acute renal failure (A,l)... 

AHF acute heart failure, CHF chronic heart failure, CRF chronic renal failure, NEP neutral endopeptidase, ECE endothelin converting enzyme, PAH pulmonary arterial hypertension. 

Erythropoietin is a growth factor produced by interstitial cells of the kidney in response to hypoxia. Erythropoietin stimulates haematopoiesis in the bone marrow. Recombinant human erythropoietin is used to treat anemias, e.g. anemia caused by chronic renal failure and anemia in AIDS and cancer patients. 

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