Diseases renal

Chronic renal disease Hypophosphatemic vitamin D-resistant rickets Vitamin D-dependent rickets... 

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). 

Esmolol is iv adrninistered. Maximal P-adrenoceptor blockade occurs in 1 min. Its elimination half-life is about 9 min. EuU recovery from P-adrenoceptor blockade is within 30 min after stopping the infusion. The therapeutic plasma concentrations are 0.4—1.2 lg/mL. It is metabolized by hydrolysis in whole blood by red blood cell esterases resulting in the formation of a primary acid metabohte and free methanol. The metabohte is pharmacologically inactive. The resulting methanol levels are not toxic. Esmolol is 55% bound to plasma protein, the acid metabohte only 10%. Less than 2% of parent dmg and the acid metabohte are excreted by the kidneys. Plasma levels may be elevated and elimination half-hves prolonged in patients with renal disease (41). 

The absorption of metoprolol after po dosing is rapid and complete. The dmg undergoes extensive first-pass metabolism in the liver and only 50% of the po dose in bioavailable. About 12% of the plasma concentration is bound to albumin. The elimination half-life is 3—7 h and less than 5% of the po dose is excreted unchanged in the urine. The excretion of the dmg does not appear to be altered in patients having renal disease (98,99,108). 

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. 

Gliptins Severe renal disease Abdominal pain, hypoglycaemia when used with another antidiabetic agent Creatinine 3... 

A class of allosteric activators of the Ca2+-sensing receptor that sensitizes the receptor to extracellular calcium and acts only in the presence but not in the absence of calcium. Calcimimetics can be used to treat various forms of hyperparathyroidism, although they are only approved for use in patients with end stage renal disease receiving dialysis treatment. 

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... 

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... 

MA M13 M13.001 Neprilysin Drug target in hypertension and renal disease... 

Dettli L (1976) Drag dosage in renal disease. Clin Pharmacokinet 1(2) 126—1115. 

Kunin CM (1967) A guide to use of antibiotics in patients with renal disease. A table of recommended doses and factors governing serum levels. Ann Intern Med 67 (1 ) 151—158... 

Renal diseases Mutations in KCNJ1 disiupt the function of Kirl.l in apical renal outer medulla of the kidney. The loss of tubular K+ channel function and impaired K+ flux could prevent apical membrane potassium recycling and lead to antenatal Bartter s syndrome. 

Penicillins should be used cautiously in patients witii renal disease, pregnancy (Pregnancy Category C), lactation (may cause diarrhea or candidiasis in die infant), and in tiiose witii a history of allergies. Any indication of sensitivity is reason for caution. The drug is also used witii caution in patients witii asthma, renal disease, bleeding disorders, and gastrointestinal disease. 

It is important to use these drag with caution in patients with a history of gastrointestinal disorders, renal disease, or liver impairment. The neuromuscular blocking action of die lincosamides poses a danger to patients widi myasthenia gravis (an autoimmune disease manifested by extreme weakness and exhaustion of die muscles). 

Thiabendazole is contraindicated in patients with known hypersensitivity. Thiabendazole is used with caution in patients with hepatic or renal disease. Thiabendazole is a Pregnancy Category C drug and is used during pregnancy only if the potential benefit outweighs the risk to the fetus. When thiabendazole is administered with the xanthine derivatives, the plasma level of the xanthine may increase to toxic levels. It is important to monitor xanthine plasma levels closely in case a dosage reduction is necessary. 

The salicylates are used cautiously in patients witii hepatic or renal disease, preexisting hypoprotiirombine-mia, or vitamin K deficiency and during lactation. The dragp are also used with caution in patients with gastrointestinal irritation such as peptic ulcers and in patients with mild diabetes or gout. 

Amantadine is used cautiously in patients with seizure disorders, hepatic disease, psychosis, cardiac disease, and renal disease The antihistamines, pheno-thiazines, disopyramide, and alcohol increase the risk of adverse reactions when administered with amantadine... 

The nitrates are used cautiously in patients witii severe hepatic or renal disease, severe head trauma, acute myocardial infarction (MI), hypotiiyroidism, and during pregnancy (Pregnancy Category C, except for amyl nitrate) or lactation. 

Goal blood pressure tor patients with diabetes is < 130/85 mm Hg Goal blood pressure tor patients wilh renal disease is < 130/85 mm Hg or < 125/75 mm Hg in palients wi1h proteinuria > 1 gram/24 hours... 

The anemias discussed in this chapter include iron deficiency anemia, anemia in patients witii chronic renal disease pernicious anemia, and anemia resulting from a folic acid deficiency. Table 45-1 defines these anemias. Drugp used in treatment of anemia are summarized in die Summary Drug Table Drugp Used in die Treatment of Anemia. 

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. 

Hyperkalemia (increase in potassium in the blood), a serious event, may be seen with the administration of potassium-sparing diuretics. Hyperkalemia is most likely to occur in patients with an inadequate fluid intake and urine output, those with diabetes or renal disease tiie elderly, and those who are severely ill. In patients taking spironolactone, gynecomastia (breast enlargement in tiie male) may occur. This reaction appears to be related to both dosage and duration of therapy. The gynecomastia is usually reversible when therapy is discontinued, but in rare instances, some breast enlargement may remain. 

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