Kidney metabohsm

Acrylonitrile is beheved to behave similarly to hydrogen cyanide (enzyme inhibition of cellular metaboHsm) (150) and is befleved to be a potential carcinogen (151). It can also affect the cardiovascular system and kidney and Hver functions (150). Eurther information on the toxicology and human exposure to acrylonitrile is available (152—154) (see Acrylonitrile). 

Magnesium. In the adult human, 50—70% of the magnesium is in the bones associated with calcium and phosphoms. The rest is widely distributed in the soft tissues and body duids. Most of the nonbone Mg ", like K", is located in the intracellular duid where it is the most abundant divalent cation. Magnesium ion is efftcientiy retained by the kidney when the plasma concentration of Mg fads in this respect it resembles Na". The functions of Na", K", Mg ", and Ca " are interrelated so that a deficiencv of Mg " affects the metaboHsm of the other three ions (26). Foods rich in magnesium are listed in Table 9. 

The potassium or calcium salt form of oxaUc acid is distributed widely ia the plant kingdom. Its name is derived from the Greek o>ys, meaning sharp or acidic, referring to the acidity common ia the foflage of certain plants (notably Oxalis and Mmex) from which it was first isolated. Other plants ia which oxahc acid is found are spinach, rhubarb, etc. Oxahc acid is a product of metabohsm of fungi or bacteria and also occurs ia human and animal urine the calcium salt is a principal constituent of kidney stones. 

Metabolism. Absorption, distribution, metaboHsm, and excretion of thioglycolic acid have been reviewed (20). In summary,. -thioglycolic acid was absorbed significantly after appHcation to the skin of rabbits. After intravenous injection, the greatest counts of radioactivity were found in the kidneys, lungs, and spleen of monkey and in the small intestine and kidneys of rat. Most of the radioactivity was rapidly excreted in the urine in the form of inorganic sulfate and neutral sulfur. 

The kidney is an important organ for the excretion of toxic materials and their metaboHtes, and measurement of these substances in urine may provide a convenient basis for monitoring the exposure of an individual to the parent compound in his or her immediate environment. The Hver has as one of its functions the metaboHsm of foreign compounds some pathways result in detoxification and others in metaboHc activation. Also, the Hver may serve as a route of elimination of toxic materials by excretion in bile. In addition to the Hver (bile) and kidney (urine) as routes of excretion, the lung may act as a route of elimination for volatile compounds. The excretion of materials in sweat, hair, and nails is usually insignificant. 

Although the antibacterial spectmm is similar for many of the sulfas, chemical modifications of the parent molecule have produced compounds with a variety of absorption, metaboHsm, tissue distribution, and excretion characteristics. Administration is typically oral or by injection. When absorbed, they tend to distribute widely in the body, be metabolized by the Hver, and excreted in the urine. Toxic reactions or untoward side effects have been characterized as blood dyscrasias crystal deposition in the kidneys, especially with insufficient urinary output and allergic sensitization. Selection of organisms resistant to the sulfonamides has been observed, but has not been correlated with cross-resistance to other antibiotic families (see Antibacterial AGENTS, synthetic-sulfonamides). 

Relatively Httie is known about the bioavailabiUty of pantothenic acid in human beings, and only approximately 50% of pantothenic acid present in the diet is actually absorbed (10). Liver, adrenal glands, kidneys, brain, and testes contain high concentrations of pantothenic acid. In healthy adults, the total amount of pantothenic acid present in whole blood is estimated to be 1 mg/L. A significant (2—7 mg/d) difference is observed among different age-group individuals with respect to pantothenic acid intake and urinary excretion, indicating differences in the rate of metaboHsm of pantothenic acid. 

In the tissues of animals, most thiamine is found as its phosphorylated esteis (4—6) and is piedominandy bound to enzymes as the pyrophosphate (5), the active coen2yme form. As expected for a factor involved in carbohydrate metaboHsm, the highest concentrations ate generally found in organs with high activity, such as the heart, kidney, Hver, and brain. In humans this typically amounts to 1—8 p.g/g of wet tissue, with lesser amounts in the skeletal muscles (35). A typical healthy human body may contain about 30 mg of thiamine in all forms, about 40—50% of this being in the muscles owing to their bulk. Almost no excess is stored. Normal human blood contains about 90 ng/mL, mostly in the ted cells and leukocytes. A value below 40 ng/mL is considered indicative of a possible deficiency. Amounts and proportions in the tissues of other animal species vary widely (31,35). 

Although it is being found that vitamin D metaboUtes play a role ia many different biological functions, metaboHsm primarily occurs to maintain the calcium homeostasis of the body. When calcium semm levels fall below the normal range, 1 a,25-dihydroxy-vitainin is made when calcium levels are at or above this level, 24,25-dihydroxycholecalciferol is made, and 1 a-hydroxylase activity is discontiaued. The calcium homeostasis mechanism iavolves a hypocalcemic stimulus, which iaduces the secretion of parathyroid hormone. This causes phosphate diuresis ia the kidney, which stimulates the 1 a-hydroxylase activity and causes the hydroxylation of 25-hydroxy-vitamin D to 1 a,25-dihydroxycholecalciferol. Parathyroid hormone and 1,25-dihydroxycholecalciferol act at the bone site cooperatively to stimulate calcium mobilization from the bone (see Hormones). Calcium blood levels are also iafluenced by the effects of the metaboUte on intestinal absorption and renal resorption. 

Clinical stresses which interfere with vitamin metabohsm, can result in calcium deficiency leading to osteomalacia and osteoporosis (secondary vitamin D deficiency). These stresses include intestinal malabsorption (lack of bile salts) stomach bypass surgery obstmctive jaundice alcoholism Hver or kidney failure decreasing hydroxylation of vitamin to active forms inborn error of metabohsm and use of anticonverdiants that may lead to increased requirement. 

Procainamide may be adininistered by iv, intramuscular (im), or po routes. After po dosing, 75—90% of the dmg is absorbed from the GI tract. About 25% of the amount absorbed undergoes first-pass metaboHsm in the fiver. The primary metabolite is A/-acetylprocainamide (NAPA) which has almost the same antiarrhythmic activity as procainamide. This is significant because the plasma concentration of NAPA relative to that of procainamide is 0.5—2.5. In terms of dmg metabolism there are two groups of patients those that rapidly acetylate and those that slowly acetylate procainamide. About 15—20% of the dmg is bound to plasma proteins. Peak plasma concentrations are achieved in 60—90 min. Therapeutic plasma concentrations are 4—10 lg/mL. Plasma half-lives of procainamide and NAPA, which are excreted mainly by the kidneys, are 2.5—4.5 and 6 h, respectively. About 50—60% is excreted as unchanged procainamide (1,2). 

About 97% of po dose is absorbed from the GI tract. The dmg undergoes extensive first-pass hepatic metaboHsm and only 12% of the po dose is bioavailable. More than 95% is protein bound and peak plasma concentrations are achieved in 2—3 h. Therapeutic plasma concentrations are 0.064—1.044 lg/mL. The dmg is metabolized in the Hver to 5-hyroxypropafenone, which has some antiarrhythmic activity, and to inactive hydroxymethoxy propafenone, glucuronides, and sulfate conjugates. Less than 1% of the po dose is excreted by the kidney unchanged. The elimination half-life is 2—12 h (32). 

Acebutolol is well absorbed from the GI tract. It undergoes extensive hepatic first-pass metabohsm. BioavailabiUty of the parent compound is about 40%. The principal metaboflte, A/-acetylacebutolol, has antiarrhythmic activity and appears to be more cardioselective. Binding to plasma proteins is only 26%. Peak plasma concentrations of acebutolol are achieved in 2.5 h, 3.5 h for A/-acetylacebutolol. The elimination half-Hves of acebutolol and its metabohte are 3—4 and 8—13 h, respectively. The compounds are excreted by the kidneys (30—40%) and by the Hver into the bile (50—60%). About 40% of the amount excreted in the urine is unchanged acebutolol, the rest as metabofltes (32). 

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). 

Metallothioneins are a group of small proteins (about 6.5 kDa), found in the cytosol of cells, particularly of liver, kidney, and intestine. They have a high content of cysteine and can bind copper, zinc, cadmium, and mercury. The SH groups of cysteine are involved in binding the metals. Acute intake (eg, by injection) of copper and of certain other metals increases the amount (induction) of these proteins in tissues, as does administration of certain hormones or cytokines. These proteins may function to store the above metals in a nontoxic form and are involved in their overall metaboHsm in the body. Sequestration of copper also diminishes the amount of this metal available to generate free radicals. 

Absorption is rapid and complete. Protein binding is between 80 to 95 percent and the elimination half life is 8 to 22 hours. It is metabolised in the liver and is excreted by the kidney. There is no presystemic metaboHsm. 

Primary regulator of calcium and phosphate metabohsm in bone and kidney... 

Biotin forms part of several enzyme systems and is necessary for normal growth and body function. Biotin functions as a cofactor for enzymes involved in carbon dioxide fixation and transfer. These reactions are important in the metaboHsm of carbohydrates, fats, and proteins, as well as promotion of the synthesis and formation of nicotinic acid, fatty acids, glycogen, and amino acids (5—7). Biotin is absorbed unchanged in the upper part of the small intestine and distributed to all tissues. Highest concentrations are found in the Hver and kidneys. Little information is available on the transport and storage of biotin in humans or animals. A biotin level in urine of approximately 160 nmol/24 h or 70 nmol/L, and a circulating level in blood, plasma, or serum of approximately 1500 pmol/L seems to indicate an adequate supply of biotin for humans. However, reported levels for biotin in the blood and urine vary widely and are not a reHable indicator of nutritional status. 

The daily dose of isoniazid is 5 mg/kg, with a maximum of 300 mg/day in adults with normal liver and kidney function. In children, 8-10 mg/kg/day is an appropriate dosage, with a maximum daily dose of 300 mg, since the metabohsm of isoniazid in children is rapid. Untoward effects of isoniazid as a single antituberculosis drug can be evaluated in preventive tuberculosis therapy, since curative regimens usually consist of multiple drugs. 

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