Excretion glomerular filtration

The tetracyclines, apart from doxycycline and minocycline, are slowly eliminated by renal excretion (glomerular filtration). Their slow elimination can be attributed to enterohepatic circulation whereby drug excreted by the liver in bile is reabsorbed from the intestine. The half-life of oxytetracycline differs widely between animal species goat (3.4 h), cattle (4.0 h), sheep (5.2 h), dog (6.0 h), pig (6.0 h), donkey (6.5 h), horse (9.6 h), and red-necked wallaby (.Macropus rufogriseus) (11.4 h). Doxycycline, unlike other tetracyclines, is eliminated by biliary excretion and diffusion into the intestine. The half-life of doxycycline is relatively short in dogs (7.0 h) and cats (4.6 h) compared with human beings (16 h). The half-life of doxycycline in chickens (4.8 h) is shorter than in turkeys (10 h) (Santos et al, 1996). Minocycline is mainly eliminated by hepatic metabolism. 

Electrolyte balance Concern about the risk of hyperkalemia associated with ACE inhibitors in patients with chronic kidney disease probably inhibits their use in such patients despite the beneficial effects of ACE inhibitors on progression of chronic kidney disease. In 1094 non-diabetic African-American adults with hypertensive chronic kidney disease, hyperkalemia was associated with increasing age, baseline protein excretion, glomerular filtration rate (GFR), and baseline potassium concentrations. Use of a potassium-wasting diuretic reduced the risk of hyperkalemia [36 ]. 

Kidney Function. Prostanoids influence a variety of kidney functions including renal blood flow, secretion of renin, glomerular filtration rate, and salt and water excretion. They do not have a critical role in modulating normal kidney function but play an important role when the kidney is under stress. Eor example, PGE2 and -I2 are renal vasodilators (70,71) and both are released as a result of various vasoconstrictor stimuli. They thus counterbalance the vasoconstrictor effects of the stimulus and prevent renal ischemia. The renal side effects of NSAIDS are primarily observed when normal kidney function is compromised. 

Technetium-99m mertiatide (A/-[Ai-[A/-[(benzoylthio)acetyl]glycyl]glycine) is a renal imaging agent. It is excreted by the kidneys via active tubular secretion and glomerular filtration. The kit vial is reconstituted by using 740—3700 MBq (20—100 mCi) of Tc pertechnetate and boiling for 10 minutes. 

As a general rule, increases of renal blood flow and/ or glomerular filtration rate (GFR) correlate rather well with increased urinary excretion of solutes and water. The underlying causes for this correlation are not fully understood, but they reflect incomplete adjustments of tubular reabsorption to an increase of tubular electrolyte load. 

Excretion via the kidney can be a straightforward question of glomerular filtration, followed by passage down the kidney tubules into the bladder. However, there can also be excretion and reabsorption across the tubular wall. This may happen if an ionized form within the tubule is converted into its nonpolar nonionized form because of a change in pH. The nonionized form can then diffuse across the tubular wall into plasma. Additionally, there are active transport systems for the excretion of lipophilic acids and bases across the wall of the proximal tubule. The antibiotic penicillin can be excreted in this way. 

The kidneys are located on the posterior part of the abdomen on either side of the spine, below the diaphragm, and behind the liver and stomach. They are bean-shaped and weigh approximately 150 grams (0.33 lb) each. The primary function of the kidneys is excretion. They work to excrete waste products through a series of steps involving glomerular filtration, secretion, and reabsorption. The kidneys also have several endocrine (e.g., production of erythropoietin and renin) and metabolic (e.g., vitamin D activation and drug metabolism) functions. 

The renal excretion of drugs depends on glomerular filtration, tubular secretion, and tubular absorption. A twofold increase in glomerular filtration occurs in the first 14 days of life [36], The glomerular filtration rate continues to increase rapidly in the neonatal period and reaches a rate of about 86 mL/min per 1.73 m2 by 3 months of age. Children 3-13 years of age have an average clearance of 134 mL/min per 1.73 m2 [37]. Tubular secretion approaches adult values between 2 and 6 months [11], There is more variability observed in maturation of tubular reabsorption capacity. This is likely linked to fluctuations in urinary pH in the neonatal period [38],... 

Atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) are members of a family of so-called natriuretic peptides, synthesized predominantly in the cardiac atrium, ventricle, and vascular endothelial cells, respectively (G13, Y2). ANP is a 28-amino-acid polypeptide hormone released into the circulation in response to atrial stretch (L3). ANP acts (Fig. 8) on the kidney to increase sodium excretion and glomerular filtration rate (GFR), to antagonize renal vasoconstriction, and to inhibit renin secretion (Ml). In the cardiovascular system, ANP antagonizes vasoconstriction and shifts fluid from the intravascular to the interstitial compartment (G14). In the adrenal cortex, ANP is a powerful inhibitor of aldosterone synthesis (E6, N3). At the hypothalamic level, ANP inhibits vasopressin secretion (S3). It has been shown that some of the effects of ANP are mediated via a newly discovered hormone, called adreno-medullin, controlling fluid and electrolyte homeostasis (S8). The diuretic and blood pressure-lowering effect of ANP may be partially due to adrenomedullin (V5). 

Renal Effects. The characteristics of early or acute lead-induced nephropathy in humans include nuclear inclusion bodies, mitochondrial changes, and cytomegaly of the proximal tubular epithelial cells dysfunction of the proximal tubules (Fanconi s syndrome) manifested as aminoaciduria, glucosuria, and phosphaturia with hypophosphatemia and increased sodium and decreased uric acid excretion. These effects appear to be reversible. Characteristics of chronic lead nephropathy include progressive interstitial fibrosis, dilation of tubules and atrophy or hyperplasia of the tubular epithelial cells, and few or no nuclear inclusion bodies, reduction in glomerular filtration rate, and azotemia. These effects are irreversible. The acute form is reported in lead-intoxicated children, whose primary exposure is via the oral route, and sometimes in lead workers. The chronic form is reported mainly in lead workers, whose primary exposure is via inhalation. Animal studies provide evidence of nephropathy similar to that which occurs in humans, particularly the acute form (see Section 2.2.3.2). 

Hypertension is more common and more severe in African Americans than in those of other races. Differences in electrolyte homeostasis, glomerular filtration rate, sodium excretion and transport mechanisms, plasma renin activity, and BP response to plasma volume expansion have been noted. 

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