Kidneys diuretic actions

Okusa MD, Ellison DH (2000) Physiology and pathophysiology of diuretic actions. In Seldin DW, Giebisch G (eds) The kidney. Physiology and pathophysiology. Lippincott Williams Wilkins, Philadelphia, p. 2877-2922... 

The diuretic action of chlorothiazide, like other drugs of this series, is caused by reduced absorption of sodium and chloride ions by the kidneys during their simultaneous, intense excretion from the organism. 

Kidney Methylxanthines exert mild diuretic action by inhibiting tubular reabsorption of sodium and water. In addition, it increases renal blood flow and glomerular filtration rate. 

A much milder and legal stimulant is caffeine, depicted in Figure 14.27. A number of mechanisms have been proposed for caffeines stimulatory effects. Perhaps the most straightforward mechanism is caffeine s facilitating of the release of norepinephrine into synaptic clefts. Caffeine also exerts many other effects on the body, such as dilation of arteries, relaxation of bronchial and gastrointestinal muscles, diuretic action on the kidneys, and stimulation of stomach-acid secretion. 

AMP is related to certain mental diseases and may be involved in the action of tranquilizers and antidepressant drugs (60). Whether the ability of diuretic agents such as ethacrynic acid and chlorthalidone to inhibit the enzyme in kidney (68) is related to their diuretic action is also not known. It has been suggested that inhibition of diesterase by diazoxide (59) may explain the hyperglycemic activity of this agent. Several materials are known to activate the enzyme. Imidazole produces strong activation of the enzyme from mammalian tissues (36, 38, 42) but not from E. coli (41). It has been reported (61) that insulin activates the beef heart enzyme in vitro, but it is not known if this has relevance... 

They act on the kidney by depressing the mechanisms that govern the active reabsorption of sodium and chloride ions. They are rapidly excreted by the kidney but their use is hazardous because their action is believed to be due to inorganic mercury ions released by rupture of the carbon-to-mercury bond, probably followed by the firm attachment of the mercury ion to a sulphydryl group of a renal enzyme. The administration of dimercaprol (SO), a strong chelating agent for mercury, removes mercury from the kidney and terminates the diuretic action. It is of interest that Paracelsus used calomel (mercurous chloride) as a diuretic. 

The nettle is rich in vitamins A and C and in minerals, particularly iron, potassium, and silica. Modern scientific studies have focused on its diuretic action. It lowers systolic blood pressure by increasing volume, die root treats symptoms of benign prostatic hyperplasia (BPH) by increasing urine flow and reducing residual urine. Nettle herb is also used for bladder irrigation and to prevent and treat bladder and kidney stones (see Chapter 66). 

Dillingham MA, Schrier RW, Greger R (1993) Mechanisms of diuretic action. In Schrier RW, Gottschalk CW (eds) Clinical Disorders of Fluid, Electrolytes, and Acid Base. Little Brown and Comp, Boston, pp 2435-2452 Fromter E (1984) Viewing the kidney through microelectrodes. Am J Physiol 247 F695-F705... 

SchlangerLE, KleymanTR, Ling BN. K(+)-sparlng diuretic actions of trimethoprim Inhibition of Na+channels In A6 distal nephron cells. Kidney International. 1994 Apr 45(4) l 070-6. 

Schlanger LE, Kleyman TR, Ling BN. K-F-sparing diuretic actions of trimethoprim inhibition of Na-F channels in A6 distal nephron cells. Kidney Int 1994 45 1070-1076. 

A) Quinidine toxicity caused by inhibition of quinidine metabohsm by the thiazide Direct effects of hydrochlorothiazide on the pacemaker of the heart Thiazide toxicity caused by the effects of quinidine on the kidneys Block of calcium current by the combination of quinidine plus thiazide Reduction of serum potassium caused by the diuretic action of hydrochlorothiazide An important therapeutic or toxic effect of loop diuretics is (A) Decreased blood volume Decreased heart rate Increased serum sodium Increased total body potassium Metabolic acidosis... 

Caffeine is a potent central stimulant. It also acts on the cardiac muscle and on the kidneys. It stimulates the higher centres of the CNS thereby causing enhanced mental alertness and wakefulness. Caffeine helps in the stimulation of respiratory centres. Its diuretic action is due to enhanced glomerular filtration rate, increased renal blood flow and above all the reduction of the normal tubular reabsorption. 

In general, the thiazide diuretics minimise the glomerular filtration rate. Furthermore, this specific action fails to contribute to the diuretic action of such drugs, and this would perhaps put forward a logical explanation of their observed lower efficacy in instances having impaired-kidney function. 

Daskalopoulos G, Kronborg I, Katkov W, Gonzalez M, Laffi G, Zipser RD. Sulindac and indomethacin suppress the diuretic action of furosemide in patients with cirrhosis and ascites evidence that sulindac affects renal prostaglandins. Am J Kidney Dis ( 9S5) 6, 217-21. 

The possibility that diuretics inhibit utilization of available high energy molecules for Na" " reabsorption has been extensively studied. The enzyme, Na -K" ATPase, is thought to be involved in energizing renal Na" " transport , but, while the diuretic action of ouabain may be explained by inhibition of this enzyme82,83j Its role in the actions of other diuretic drugs is not certaln, it is clear, however, that EA and furosemide somehow interfere with renal medullary energy utilization since ATP levels in this part of the kidney are elevated by these compounds . Inhibition of Na -K ATPase could produce this buildup. On the other hand, such effects certainly would not result from reduced oxidative or anaerobic metabolism. 

C7H9N402- M.p. 337 C, an alkaloid obtained from cacao seeds or prepared synthetically. Constitutionally it is similar to caffeine, and is also a weak base. It is usually administered as the sodium compound combined with either sodium ethanoate or sodium salicylate, and is employed almost entirely as a diuretic. Physiologically theobromine resembles caffeine, but its effect on the central nervous system is less, while its action on the kidneys, is more pronounced. 

Calcium channel blockers cause more pronounced lowering of blood pressure in hypertensive patients than in normotensive individuals. Generally, all calcium channel blockers cause an immediate increase in PRA during acute treatment in patients having hypertension but PRA is normalized during chronic treatment despite the sustained decrease in blood pressure. These agents also do not generally produce sodium and water retention, unlike the conventional vasodilators. This is because they produce diuretic effects by direct actions on the kidney. 

Figure 46-1. The nephron is the functional unit of the kidney. Note the various tubules, the site of most diuretic activity. The loop of Henle is the site of action for the loop diuretics. Thiazide diuretics ad at the ascending portion of the loop of Henle and the distal tube of the nephron.

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. 

Caffeine and the related dimethylxanthines have similar pharmacological or therapeutic effects and similar toxic effects. The primary actions include stimulation of the central nervous system, relaxation of bronchial muscles, mild cardiac muscle stimulation, and diuretic effects on the kidney. 

Natiuretic response to diuretics including fruse-mide and bumetanide is reduced as a result of decreased renal tubular secretion of diuretic Thus, age-related changes in renal tubular function may influence not only pharmacokinetics but also drug action on the kidney (pharmacodynamics). 

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