Excretion General principles

One of the factors that can alter the response to drugs is the concurrent administration of other drugs. There are several mechanisms by which drugs may interact, but most can be categorized as pharmacokinetic (absorption, distribution, metabolism, excretion), pharmacodynamic (additive or antagonistic effects), or combined interactions. The general principles of pharmacokinetics are discussed in Chapters 3 and 4 the general principles of pharmacodynamics in Chapter... 

The general principle of biotransformation is the metabolic conversion of drug molecules to more water-soluble metabolites that are more readily excreted. 

The answer is b. (Hardman, pp 695-697.) A significant increase in the amount of any osmotically active solute in voided urine is usually accompanied by an increase in urine volume Osmotic diuretics affect diuresis through this principle. The osmotic diuretics (such as mannitol) are nonelectrolytes that are freely filtered at the glomerulus, undergo limited re absorption by the renal tubules, retain water in the renal tubule, and promote an osmotic diuresis, generally without significant Na excretion. Ln addition, these diuretics resist alteration by metabolic processes. 

In principle, any kind of limitation of the medium (e.g. due to some kind of clustering in a zone) tends to diminish the individual uptake rate [31]. From the point of view of modelling, the breaking of the symmetry rapidly complicates the problem (see Chapter 3 in this volume). As an exception to the general rule of decreased uptake due to inter-cell competition, it has been shown [49] that biouptake through siderophore excretion is only viable for nonisolated cells. 

In general, drug metabolism serves to inactivate a substrate and increase water solubility of the substrate for excretion, bioactivate a substrate or prodrug (e.g., codeine and cyclophosphamide) to an active or mutagenic principle, or less commonly, extend the elimination half-life of a pharmacologically active or potentially toxic metabohte. Metabolic reactions are often divided into Phase I and Phase II categories, as depicted in Figure 43-1. 

The conversion of cholesterol into bile acids represents the most obvious example of the high capacity of the liver to convert lipid-soluble material into excretable water-soluble products. In principle, the reactions in the formation of bUe acids are very similar to those generally involved in the metabolism and detoxication of various lipids and drugs hydroxylations, oxidations, and conjugations. In contrast to detoxication reactions, however, some of the reactions are highly specific and at least one of the hydroxylations is subject to metabolic control. In view of the importance of the rate of elimination of cholesterol in diseases such as atherosclero-... 

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