Osmotic agents, excretion

A low concentration (0.01% for BZC and 0.1% for PS) of these materials can lead to nasal lesions in the rat however, this level is known as safe for human nasal mucosa exposure Related to the composition of the diet along with stress of pregnancy, parturition, and lactation (not seen with same diet in males and nonpregnant females) daily gavage administration of lOmL/kg of corn oil is not recommended to pregnant rats Cause of toxicity is not clearly understood but, in part, may be related to an adaptive response due to excretion of osmotic agents at extremely high concentration parenteral use of a- and (t-CDs is not recommended... 

Renal Issues. The parent CDs can all show a toxic effect on the kidney when given parenterally. The nephrotoxicity of a- and p-CD manifests itself as a series of alterations in the organelles of the proximal tubule cells. ° The toxicity is initially expressed as an increase in apical vacuoles, which is typical of an adaptive response tothe excretion of osmotic agents at extremely high concentrations. This effect reverses upon discontinuation of CD administration. However, there are also other cellular changes not typical of... 

Diuretics are a group of therapeutic agents designed to reduce the volume of body fluids. Their mechanism of action is at the level of the kidney and involves an increase in the excretion of Na+ and Cl ions and, consequently, an increase in urine production. As discussed in Chapter 2, sodium is the predominant extracellular cation and, due to its osmotic effects, a primary determinant of extracellular fluid volume. Therefore, if more sodium is excreted in the urine, then more water is also lost, thus reducing the volume of extracellular fluids including the plasma. 

Modern diuretics (natriuretics, saluretics), as used in the treatment of hypertension and heart failure, are administered with the aim to enhance the renal excretion of sodium ions and water. Older diuretics, such as the osmotic diuretic agents, are of little interest in the treatment of the aforementioned cardiovascular disorders, but may be used to lower intracranial pressure associated with brain edema. 

Other drugs, such as verapamil, caffeine, theophylline, osmotic diuretics, carbonic anhydrase inhibitors, or aminophylline, can increase lithium excretion, possibly dropping plasma levels below the therapeutic threshold ( 329). Further, if doses are increased to compensate for this effect, care must be taken to readjust the lithium downward when these concomitant agents are reduced or discontinued. 

Technically, a "diuretic" is an agent that increases urine volume, whereas a "natriuretic" causes an increase in renal sodium excretion. Because natriuretics almost always also increase water excretion, they are usually called diuretics. Osmotic diuretics (see under Agents That Alter Water Excretion) are diuretics that are not directly natriuretic. 

Agents That Alter Water Excretion OSMOTIC DIURETICS... 

Osmotic diuretics are used to increase water excretion in preference to sodium excretion. This effect can be useful when avid Na + retention limits the response to conventional agents. It can be used to maintain urine volume and to prevent anuria that might otherwise result from presentation of large pigment loads to the kidney (eg, from hemolysis or rhabdomyolysis). Some oliguric patients do not respond to osmotic diuretics. Therefore, a test dose of mannitol (12.5 g intravenously) should be given before starting... 

An ideal contrast agent should have the following properties fa) ready availability and low cost fb) excellent x-n> absorption characteristics at the x-ray eneigies used in diagnostic radiology (c) minimal toxicity and ready patient acceptance (d) chemical stability fe) high water solubility ilh low viscosity and no significant osmotic effects and ifi the ability to be administered for selective tissue uptake cod excretion. 

Contrast agents cause osmotic diuresis. Studies show that sodium diatrizoate is excreted in higher concentration in the urine than is meglumine diatrizoate because of resorption of sodium ions in the renal tubules. Benness (790, 878) reported a difference in roentgenographic quality in pyelogramsin favor of sodium contrast agents. 

Nearly all bile acids are choleretic agents that is, they increase bile flow when infused intravenously into various animal species. In all vertebrtae species examined, there is a close relationship between bile flow and the hepatic excretion rate of bile acids (B24). Acute interruption of the enterohepatic circulation of bile acids in man by diversion of bile flow causes the rate of bile secretion to decrease by about 50% (TIO). Thus, the excretion of bile acids from the liver is the major determinant of bile water and solute excretion, predominantly because of the osmotic activity of bile acids in bile. Some interesting studies in dogs have been performed with the bile salt taurodehydrocholate (taurine conjugate of 3,7,12-triketo-5fl-cholan-24-oic acid), which, for stereochemical reasons, cannot form micelles and should therefore have greater osmotic activity than other bile acids. At the same... 

Most of the renal tubular reabsorption ofU occurs in the proximal tubule. Nevertheless, Id retention can be increased by any diuretic that leads to depletion of Na, particularly the thiazides (see Chapter 28). Renal excretion can be increased by administration of osmotic diuretics, aceta-zolamide or aminophylline, and triamterene. Spironolactone does not increase the excretion of LiL Some nonsteroidal anti-inflammatory agents can facilitate renal proximal tubular resorption of Id and thereby increase concentrations in plasma to toxic levels. This interaction appears to be particularly prominent with indomethacin, but also may occur with ibuprofen, naproxen, and COX-2 inhibitors, and possibly less so with sulindac and aspirin. A potential drug interaction can occur with angiotensin-converting enzyme inhibitors, causing lithium retention (see Chapter 29). 

Taurocholate is able to form micelles infusion of TC has been shown [232] to increase output of phospholipid and cholesterol with which it forms mixed micelles. Dehydrocholate has a low tendency to micelle formation and has little influence on the biliary excretion of cholesterol and phospholipid. However, Hardison and Apter [233] have found that while micelle formation is an important factor in the biliary excretion of lipids, it cannot alone explain the results they have obtained. Dehydrocholate, a synthetic agent, is a potent choleretic presumably because its osmotic activity in bile is not diminished by micelle formation and it may therefore exert an osmotic force in biliary canaliculae approximately equal to its concentration. As a result, bile flow is increased more by this substance than by micelle-forming bile salts. Some metabolites of dehydrocholate are, however, capable of micelle formation [234,235]. 

Day-long-duration, osmotically actuated tablets, for oral administration of many rapidly metabolized/excreted agents (16). 

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