Diuretic agents osmotic diuretics

Many diuretic agents (loop diuretics, thiazides, amiloride, and triamterene) exert their effects on specific membrane transport proteins in renal tubular epithelial cells. Other diuretics exert osmotic effects that prevent water reabsorption (mannitol), inhibit enzymes (acetazolamide), or interfere with hormone receptors in renal epithelial cells (spironolactone). 

Manufacture of vitamin C starts with the conversion of sorbitol to L-sorbose. Sorbitol and xyHtol have been used for parenteral nutrition following severe injury, bums, or surgery (246). An iron—sorbitol—citric acid complex is an intramuscular bematinic (247). Mannitol administered intravenously (248) and isosorbide administered orally (249) are osmotic diuretics. Mannitol hexanitrate and isosorbide dinitrate are antianginal dmgs (see Cardiovascular agents). 

Mannitol is an agent that may be used in patients with I impending cerebral herniation. Mannitol is an osmotic diuretic that shifts brain osmolarity from the brain to the blood. Doses of 100 g (1-2 g/kg) as an intravenous bolus should be used. Repeated doses typically are not recommended because mannitol may diffuse into damaged brain tissue, leading to rebound increased ICP.21... 

Forced diuresis is occasionally useful. It may cause volume overload or electrolyte disturbances. Forced diuresis is useful for phenobarbital, bromides, lithium, salicylate, or amphetamines overdoses. Do not use for tricyclic antidepressants, sedative-hypnotics, or highly protein-bound medications. The most common agents employed are furosemide and osmotic diuretics with mannitol. 

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. 

Ideally, the distribution of osmotic diuretics should be largely confined to the vascular system, although this can lead to excessive expansion of the vascular compartment. Such an overexpansion could precipitate pulmonary edema or increase cardiac work or both. This is largely the result of rapid transfer of fluid from the interstitial to the vascular compartment. Practically speaking, however, few osmotic diuretics are available for therapeutic use. These agents, therefore, should be given cautiously to patients with compromised cardiac function. 

Mechanism of Action An osmotic diuretic, antiglaucoma, and antihemolytic agent that elevates osmotic pressure of theglomerular filtrate, inhibiting tubular reabsorption of water and electrolytes, resulting in increased flow of water into interstitial fluid and plasma. Therapeutic Effect Produces diuresis reduces lOP reduces iCP and cerebral 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... 

The proximal tubule and descending limb of Henle s loop are freely permeable to water (Table 15-1). Any osmotically active agent that is filtered by the glomerulus but not reabsorbed causes water to be retained in these segments and promotes a water diuresis. Such agents can be used to reduce intracranial pressure and to promote prompt removal of renal toxins. The prototypic osmotic diuretic is mannitol. 

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... 

Osmotically acting diuretic agents. These are applied in the treatment of intoxication in order to increase the urine volume and accelerate elimination of the poison ( forced diuresis ). The classical example is mannitol. This sugar is quite similar to glucose in structure but does not get metabolized nor reabsorbed from the primary glomerular filtrate in the kidneys. 

Therapeutically, mannitol administered parenterally is used as an osmotic diuretic, as a diagnostic agent for kidney function, as an adjunct in the treatment of acute renal failure, and as an agent to reduce intracranial pressure, treat cerebral edema, and reduce intraocular pressure. Given orally, mannitol is not absorbed significantly from the GI tract, but in large doses it can cause osmotic diarrhea see Section 14. 

The osmotic diuretics (e.g. mannitol, sucrose, urea and glycerol) are agents that are filtered freely in the glomeruli, reabsorbed poorly in the tubules and pharmacologically inert. As sodium and water are reabsorbed in the proximal tubule and the loop of Henle, the osmotic diuretics are... 

Dimethyl sulfoxide (DMSO) has also been suggested as a potent osmotic diuretic in horses. However, one study that compared the diuretic effects of DMSO with furosemide (frusemide, Img/kg) and hypertonic saline (5 liters) found that DMSO (Ig/kg administered i.v. diluted in 5 liters of 0.9% sodium chloride) was a relatively weak diuretic agent that doubled 4-h urine production in comparison with that achieved with the same volume of isotonic (0.9%) sodium chloride. The most dramatic diuretic response was produced by the hypertonic saline (7.5%), which resulted in the production of more than 40 ml/kg urine during the first 4-h period after administration (Schott Black 1995). 

DERMATOLOGICAL AGENT in a number of skin preparations, e.g. to treat eczema and psoriasis (as a hydrating agent). It can be given intravenously as a hypertonic dehydrating (osmotic) diuretic to reduce intracranial pressure in controlling cerebral oedema. 

Malignant neoplasms Fanconi s syndrome Acute volume expansion Metabolic acidosis Renal transplantation Vitamin D deficiency and/or resistance Diuretics Acetazolamide Osmotic agents Glucocorticoids Sodium bicarbonate Internal redistribution Refeeding syndrome Parenteral nutrition... 

Glycerin is a hyperosmotic/osmotic diuretic/ophthahnic agent that reduces intraocular pressure (lOP) by creating an... 

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). 

Mannitol is the agent most commonly used as an osmotic diuretic. Sorbitol also can be used for similar reasons. These compounds can be prepared by the electrolytic reduction of glucose or sucrose. 

Readily obt. from glucose. By-prod, of the starch industry obt. by dehydration of Glucitol, G-247. Inexpensive starting material for synthesis. Osmotic diuretic. Used in the treatment of hydrocephalus. Also a chiral modifying agent for asymmetric redn. of ketones. Mp 62-64°. Bp2 160-175°. Mg +44.8 (HjO). 

TRIS is one of the most common buffers used in the biology/biochemistry labs. It is used as alternative to sodium bicarbonate in the treatment of metabolic acidosis. It is also an emulsifying agent and absorbent for acidic gases, alkalizer and osmotic diuretic. 

The high osmolality of CM explains another important feature of these agents. They are osmotic active and act similar to osmotic diuretics such as mannitol. After administration, an increased diuresis is observed. This observation supports the necessity to perform hydration of the patient not only before, but also after administration of CM to balance the CM-induced diuresis. The histological lesions in the kidney are of the same type as the lesions observed after administration of mannitol or other agents inducing osmotic diuresis. 

C4H11NO3 M 121.136 Used in the synth. of surfactants, vulcanisation accelerators and pharmaceuticals. Also a titrimetric standard, emulsifying agent and absorbent for acidic gases. Alkalizer and osmotic diuretic. Buffer component, acidimetric standard. Cryst. mass. Sol. H2O, EtOH, insol. Et20. Mp 171-172°. Bpio 219-220°. pK 8.08 (25°). > Irritant. TY2900000. 

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