Reabsorption, passive renal

The answer is a. (Hardman, pp 16-20.) Sodium bicarbonate is excreted principally in the urine and alkalinizes it. Increasing urinary pH interferes with the passive renal tubular reabsorption of organic acids (such as aspirin and phenobarbital) by increasing the ionic form of the drug in the tubular filtrate. This would increase their excretion. Excretion of organic bases (such as amphetamine, cocaine, phencyclidine, and morphine) would be enhanced by acidifying the urine. 

The question arises as to whether species differences also exist for passive renal excretion processes. Indeed, some more or less systematic and therefore controllable differences do exist. The urinary pH tends to be more acidic in carnivores than in herbivores. Due to differences in the degree of ionization, passive renal reabsorption of weak bases and acids thus will differ for the species mentioned, but in a reasonably predictable way. Also the degree of binding of the pharmacon to plasma albumin will influence the rate of renal excretion. 

The major processes involved in renal excretion are glomerular filtration, active tubular secretion, and passive reabsorption. Overall, renal excretion results from the net contributions of these three processes ... 

A) Drugs that are ionized in the renal tubule are more likely to undergo passive reabsorption than those that are unionized... 

Osmotic diuretics are non-electrolytes, freely filterable at the glomerulus, undergo limited reabsorption by the renal tubules. The amount of diuresis produced is proportional to the quantity of osmotic diuretic, therefore for more diuresis, a large quantity of osmotic diuretic should be given. The primary effect of osmotic diuretics involves an increased fluid loss caused by osmotically active diuretic molecule. This results in reduced reabsorption of sodium and water in proximal tubule and since the tubule is permeable to water, there is a passive back diffusion of water, such a process keeps the tubular fluid isotonic. 

The processes of selective reabsorption of nutrients and xenobiotics goes on within the complex tubule system. 98-99% of filtered materials (salts, water, sugars, amino acids) are eventually reabsorbed by passive or active transport. Biomolecules such as glucose and amino acids are entirely reabsorbed if their concentrations are within the normal range in the blood. However, should the concentrations be higher than normal, those molecules might not be completely reabsorbed because they have exceeded the ability of the nephron transport systems to accommodate them. This is referred to as exceeding the renal threshold. Urine is therefore a convenient body fluid to assay for the initial assessment of metabolic or excretory system malfunctions. 

Mineralocorticoids are believed to increase sodium reabsorption by affecting sodium channels and sodium pumps on the epithelial cells lining the renal tubules.18,58 Mineralocorticoids ability to increase the expression of sodium channels is illustrated in Figure 29-5. These hormones enter the tubular epithelial cell, bind to receptors in the cell, and create an activated hormone-receptor complex.18 This complex then travels to the nucleus to initiate transcription of messenger RNA units, which are translated into specific membrane-related proteins.27,58 These proteins in some way either create or help open sodium pores on the cell membrane, thus allowing sodium to leave the tubule and enter the epithelial cell by passive diffusion.27,83 Sodium is then actively transported out of the cell and reabsorbed into the bloodstream. Water reabsorption is increased as water follows the sodium movement back into the bloodstream. As sodium is reabsorbed, potassium is secreted by a sodium-potassium exchange, thus increasing potassium excretion (see Fig. 29-5). 

Interference with passive diffusion (see p. 96). Reabsorption of a drug by the renal tubule can be reduced, and its excretion increased, by altering urine pH (see Drug overdose, p. 155). 

Although diastereoisomers, both quinine and quinidine, have similar physical properties (Fig. 18). In clinical studies, the renal clearance of quinidine was fourfold greater than that of quinine (57). No stereoselective differences in plasma protein binding were observed. The renal filtration and passive reabsorption of these two diastereoisomers should be similar since the compounds have similar octanol-water partition coefficients and pKa values (57). Therefore, stereoselective active renal secretion may be the mechanism responsible for the observed differences in the renal clearances of quinine and quinidine. 

A reasonable assumption is that the active secretion mechanism in the kidney can also be described by the well-stirred model. However, the kidneys have several mechanisms that may determine renal clearance of a drug, including passive filtration and reabsorption. 

Figure 10.4 (a) A highly simplified diagram of a kidney tubule to illustrate the filtration and secretion of drugs from the blood into the tubular filtrate, and their subsequent reabsorption or loss in the urine, (b) Schematic representation of the influence of urinary pH on the passive reabsorption of a weak acid and a weak base from the urine in the renal tubules at a high pH the passive reabsorption of the weak base and the excretion of the weak acid are enhanced, while at a low pH values the reabsorption of the weak acid and the excretion of the weak base ore enhanced. 

Salicylate and its metabolites are rapidly and almost completely excreted in the urine by glomerular filtration and by renal tubular secretion. Passive reabsorption of salicylate occurs in the distal tubules. Salicylate elimination is saturable and characterized by Michaelis-Menton kinetics where the elimination half-life is dependent on the dose. Since the pRa of salicylic acid is 3, its renal clearance is greatly influenced by changes in urinary pH. Increasing urinary pH can significantly increase the overall salicylate elimination rate via ion trapping. 

Here too, species differences are reported, but this parameter is accessible to in vitro studies. Both protein-binding and passive reabsorption, factors that determine the rate of renal excretion, are related to the partition coefficients of the compounds119,12°. The half-life of various non- or poorly metabolized sulfanilamides is strongly dependent on the partition coefficient, as can be seen from Fig. 13121. ... 

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