Renal excretion Urine

Aceta2olamide, the best example of this class of diuretics (69,70), is rarely used as a diuretic since the introduction of the thia2ides. Its main use is for the treatment of glaucoma and some minor uses, eg, for the a1ka1ini2ation of the urine to accelerate the renal excretion of some weak acidic dmgs, and for the prevention of acute high altitude mountain sickness. 

Excretion is the process by which a substance leaves the body. The most common ways are via the kidneys and via the gut. Renal excretion is favored by water-soluble compounds that can be filtered (passively by the glomeruli) or secreted (actively by the tubuli) and that are collected into urine. Fecal excretion is followed by more lipid substances that are excreted from the liver into the bile, which is collected in the gut and passed out by the feces. Other routes of excretion are available through the skin and the lungs. 

Nitrogen compounds commonly determined are creatinine, urea, and uric acid. Creatinine is an end product of the energy process occurring within the muscles, and is thus related to muscle mass. Creatinine in urine is commonly used as an indicator and correction factor of dilution in urine. Creatinine in serum is an indicator of the filtration capacity of the kidney. Urea is the end product of the nitrogen luea cycle, starting with carbon dioxide and ammonia, and is the bulk compoimd of urine. The production of uric acid is associated with the disease gout. In some cases, it appears that the excess of uric acid is a consequence of impaired renal excretion of this substance. 

Pharmacodynamics Duration 1-4 weeks Absorption IM slow Time to peak serum levels 12-24 hours Duration 15-24 hours Absorption IM slow Distribution Poor blood-brain barrier penetration, enters breast milk Metabolism =30% hepatic inactivation Protein binding 65% Time to peak serum levels 1-4 hours Excretion Urine (60-90% as unchanged drug) Clearance Renal... 

The maintenance of plasma volume and plasma osmolarity occurs through regulation of the renal excretion of sodium, chloride, and water. Each of these substances is freely filtered from the glomerulus and reabsorbed from the tubule none is secreted. Because salt and water intake in the diet may vary widely, the renal excretion of these substances is also highly variable. In other words, the kidneys must be able to produce a wide range of urine concentrations and urine volumes. The most dilute urine produced by humans is 65 to 70 mOsm/1 and the most concentrated the urine can be is 1200 mOsm/1 (recall that the plasma osmolarity is 290 mOsm/1). The volume of urine produced per day depends largely upon fluid intake. As fluid intake increases, urine output increases to excrete the excess water. Conversely, as fluid intake decreases or as an individual becomes dehydrated, urine output decreases in order to conserve water. 

An overall increase in sympathetic nerve activity includes an increase in sympathetic input to the kidneys. Consequently, resistance of the afferent arteriole increases, leading to a decrease in RBF. As discussed, this results in a decrease in PGC, GFR, and urine output. As such, the renal excretion of sodium and water is decreased. In other words, sodium and water are... 

Hydroxylated metabolites are conjugated as glucuronides and sulfates. The balance of products in this last step and their distribution between urine and feces distinguishes the metabolism between humans, rats, and rabbits (Baldwin and Hutson 1980 Bedford et al. 1975b Hutson 1981 Hutson et al. 1975), as discussed in Section 2.3.4. Similarly, studies in lactating cows ingesting radio-labeled endrin in the diet for 21 days suggest metabolic pathways similar to those in rats and rabbits with apparent differences between the 3 species attributed more to differences in biliary versus renal excretion (Baldwin et al. 1976). 

Renal clearance of cotinine is much less than the glomerular filtration rate (Benowitz et al. 2008b). Since cotinine is not appreciably protein bound, this indicates extensive tnbnlar reabsorption. Renal clearance of cotinine can be enhanced by np to 50% with extreme urinary acidification. Cotinine excretion is less influenced by urinary pH than nicotine becanse it is less basic and, therefore, is primarily in the unionized form within the physiological pH range. As is the case for nicotine, the rate of excretion of cotinine is influenced by urinary flow rate. Renal excretion of cotinine is a minor route of elimination, averaging about 12% of total clearance. In contrast, 100% of nicotine Ai -oxide and 63% of 3 -hydroxycotinine are excreted unchanged in the urine (Benowitz and Jacob 2001 Park et al. 1993). 

The human body has a number of different pH environments. For example, blood plasma has a rigorously controlled pH of 7.4 (see Box 4.9), the gastric juice is usually strongly acidic (pH from about 1 to 7), and urine can vary from about 4.8 to 7.5. It is possible to predict the qualitative effect of pH changes on the distribution of weakly acidic and basic dmgs, especially in relation to gastric absorption and renal excretion ... 

Ammonia can diffuse freely into the urine through the tubule membrane, while the ammonium ions that are formed in the urine are charged and can no longer return to the cell. Acidic urine therefore promotes ammonia excretion, which is normally 30-50 mmol per day. In metabolic acidosis (e.g., during fasting or in diabetes mellitus), after a certain time increased induction of glutaminase occurs in the kidneys, resulting in increased NH3 excretion. This in turn promotes H"" release and thus counteracts the acidosis. By contrast, when the plasma pH value shifts towards alkaline values alkalosis), renal excretion of ammonia is reduced. 

Excretion - Miglitol is eliminated by renal excretion as unchanged drug. Following a 25 mg dose, more than 95% of the dose is recovered in the urine within 24 hours. The elimination half-life from plasma is approximately 2 hours. 

Metaboiism/Excretion - Fluconazole is cleared primarily by renal excretion, with approximately 80% of the dose appearing in the urine unchanged, approximately 11% as metabolites. The dose may need to be reduced in patients with impaired renal function. A 3-hour hemodialysis session decreases plasma concentrations by approximately 50%. 

Excretion - Absorbed oseltamivir is primarily (more than 90%) eliminated by conversion to oseltamivir carboxylate. Plasma concentrations of oseltamivir declined with a half-life of 1 to 3 hours in most subjects after oral administration. Oseltamivir carboxylate is not further metabolized and is eliminated in the urine. Plasma concentrations of oseltamivir carboxylate declined with a half-life of 6 to 10 hours in most subjects. Oseltamivir carboxylate is eliminated entirely (more than 99%) by renal excretion. Renal clearance (18.8 L/h) exceeds glomerular filtration rate (7.5 L/h) indicating that tubular secretion occurs, in addition to glomerular filtration. Less than 20% of an oral dose is eliminated in feces. 

Dermatologic reactions Dermatologic reactions may occur exercise care when given to any patient receiving a drug with significant tendency to produce dermatitis. Toxic symptoms If serious toxic symptoms occur, administer ammonium chloride (8 g daily in divided doses for adults) 3 or 4 days a week for several months after therapy has been stopped acidification of the urine increases renal excretion by 20% to 90%. Exercise caution in renal function impairment and/or metabolic acidosis. 

Metabolites of the cholinesterase inhibitors and in some instances significant amounts of the parent compound are eliminated in the urine. Renal excretion is very important in the clearance of agents such as neostigmine, pyridostigmine, and edrophonium. This is demonstrated by a twofold to threefold increase in elimination half-lives for these drugs in anephric patients. Renal elimination is largely the result of glomerular filtration but probably also involves, at least in the case of quaternary amines, secretion via the renal cationic transport system. 

The major route of fluoride excretion is via the kidney and urine 40-60% of the daily intake is excreted in the urine with an elimination half-life of about 5 h [17,85]. Fluoride excretion is influenced by a number of factors, including glomerular filtration rate, urinary flow and urinary pH. The excretion of fluoride in urine is reduced in individuals with impaired renal function. Urine fluoride excretion is 0.79 mg/day in humans with normal renal function, 0.53 mg/day in those with questionable and 0.27 mg/day in those with impaired renal function [86],... 

Elimination of clonidine is 65% by renal excretion and 35% by liver metabolism, while guanfacine and its metabolites are excreted primarily in the urine, with approximately 50% as unchanged drug. These differences in elimination may account for differences in the pharmacodynamic properties of the two drugs. The behavioral effects of clonidine last only 3 to 6... 

Acidify the urine to enhance the renal excretion of morphine. 

Uric acid, cystine, and other weak acids are most easily reabsorbed from acidic urine. Therefore, renal excretion of cystine (in... 

Nitrofurantoin is well absorbed after ingestion. It is metabolized and excreted so rapidly that no systemic antibacterial action is achieved. The drug is excreted into the urine by both glomerular filtration and tubular secretion. With average daily doses, concentrations of 200 mcg/mL are reached in urine. In renal failure, urine levels are insufficient for antibacterial action, but high blood levels may cause toxicity. Nitrofurantoin is contraindicated in patients with significant renal insufficiency. 

Two bismuth compounds are available bismuth subsalicylate, a nonprescription formulation containing bismuth and salicylate, and bismuth subcitrate potassium. In the USA, bismuth subcitrate is available only as a combination prescription product that also contains metronidazole and tetracycline for the treatment of H pylori. Bismuth subsalicylate undergoes rapid dissociation within the stomach, allowing absorption of salicylate. Over 99% of the bismuth appears in the stool. Although minimal (< 1%), bismuth is absorbed it is stored in many tissues and has slow renal excretion. Salicylate (like aspirin) is readily absorbed and excreted in the urine. 

Metabolism inducible. Inhibits CYP2D6. Renal excretion susceptible to changes in urine pH. Additive effects with other agents that prolong the QTC interval. 

Distribution of penicillin antibiotics is limited to extracellular fluids, but inflammation may enhance their distribution into tissues. Penicillins are actively transported in kidney, brain, and liver. Most penicillins undergo minimal hepatic metabolism and are cleared from the plasma primarily by renal excretion. Secretion of penicillins by the renal tubules results in high urine concentrations and rapid elimination from the body (50). 

Following intramuscular administration to sheep of 1 mg xylazine/kg bw, two-thirds of the injected dose could be absorbed within 10 min (113). The drug was rapidly distributed to different tissues, and rapidly eliminated. The rapid elimination of xylazine in sheep is probably related to its intense metabolism rather than to its rapid renal excretion. This hypothesis was supported by the lack of significant amounts of the intact drug in urine samples collected every 10 min from treated sheep. 

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