Bicarbonate diuretic

Filtered sodium is reabsorbed at the proximal tubules, the Loop of Henle, distal tubules, or in the collecting tubules. Diuretics influence tubules closest to the glomeruli, causing natriuresis (sodium loss in the urine). Diuretics cause loss of other electrolytes (potassium, magnesium, chloride, bicarbonate). Diuretics that promote potassium excretion are called potassium-wasting diuretics or potassium-sparing diuretics. 

Bicarbonate diuretic A diuretic that selectively increases sodium bicarbonate excretion. Example a carbonic anhydrase inhibitor... 

The K-sparing group of diuretics produce their diuretic response by reduction of the reabsorption of Na in the later distal convoluted tubule and the collecting duct. They cause an increase in the urinary excretion of NaCl and possibly bicarbonate, while they reduce the excretion of K. The K-sparing diuretic agents do not appear to have any significant effect on the excretion of Mg and Ca ions. 

The answer is c. (Hardman, pp 6917 693 J Acetazolamide is a carbonic anhydrase inhibitor with its primary site of action at the proximal tubule of the nephron. Acetazolamide promotes a urinary excretion of Na, K, and bicarbonate There is a decrease in loss of Cl ions The increased excretion of bicarbonate makes the urine alkaline and may produce metabolic acidosis as a consequence of the loss of bicarbonate from the blood. None of the other diuretic drugs promote a reduction in the excretion of the Cl ion... 

Metabolic alkalosis is initiated by increased pH and I ICC)3, which can result from loss of H+ via the GI tract (e.g., nasogastric suctioning, vomiting) or kidneys (e.g., diuretics, Cushing s syndrome), or from gain of bicarbonate (e.g., administration of bicarbonate, acetate, lactate, or citrate). 

In metabolic alkalosis and respiratory acidosis, pH does not usually deviate significantly from normal, but treatment can be required to maintain Pao2 and PaC02 at acceptable levels. Treatment should be aimed at decreasing plasma bicarbonate with sodium and potassium chloride therapy, allowing renal excretion of retained bicarbonate from diuretic-induced metabolic alkalosis. 

Another important diuretic contains both triamterene and hydrochlorothiazide. Triamterene is a diuretic and is known to increase sodium and chloride ion excretion but not potassium ion. It is used in conjunction with a hydrothiazide, which is an excellent diuretic but also gives significant loss of potassium and bicarbonate ions. If the triamterene were not included potassium chloride would have to be added to the diet. Hydrochlorothiazide is an antihypertensive agent as well but, unlike other antihypertensives, it lowers blood pressure only when it is too high, and not in normotensive individuals. These two drugs are made by a number of different manufacturers and do not appear in our top 35 list, but they would rank high if all brands were combined. 

This potassium sparing diuretic causes a moderate increase in excretion of sodium and bicarbonate ions in urine, and it raises excretion of potassium and ammonia ions. It has little effect on urine volume. 

Pharmacology Thiazide diuretics increase the urinary excretion of sodium and chloride in approximately equivalent amounts. They inhibit reabsorption of sodium and chloride in the cortical thick ascending limb of the loop of Henie and the early distal tubules. Other common actions include Increased potassium and bicarbonate excretion, decreased calcium excretion and uric acid retention. At maximal therapeutic dosages all thiazides are approximately equal in diuretic efficacy. 

Inhibition of proximal tubule brush border carbonic anhydrase decreases bicarbonate reabsorption, and this accounts for their diuretic effect. In addition, carbonic anhydrase inhibitors affect both distal tubule and collecting duct H+ secretion by inhibiting intracellular carbonic anhydrase. 

Furosemide (Lasix), torsemide (Demadex), and bumetanide (Bumex) possess some carbonic anhydrase inhibiting activity (about one-tenth that of chlorothiazide). This property may account for the increased bicarbonate and phosphate excretion seen after large doses of these diuretics. The elevated HCOj" loss probably indicates some proximal tubular effects for furosemide and bumetanide. 

In the AN patients who engage in self-induced vomiting or abuse laxatives and diuretics, hypokalemic alkalosis may develop. These patients often have elevated serum bicarbonate, hypochloremia, and hypokalemia. 

Acetazolamide (a carbonic anhydrase inhibitor) used as diuretic by increasing bicarbonate excretion and thus acidosis occur as side effect which is related to its pharmacological action. 

Acidosis and alkalosis are infrequent. Metabolic acidosis is a side effect of acetazolamide therapy and is due to bicarbonate loss in the PCT. All the K+-sparing diuretics can cause metabolic acidosis by H+ retention in the cells of the collecting duct. Metabolic alkalosis is associated with the loop and thiazide drugs. Reflex responses to volume depletion cause reabsorption of HCO-3 in the PCT and H+ secretion in the collecting tubule. 

Acetazolamide is a diuretic whose main action is the inhibition of carbonic anhydrase (see Chapter 15). Mild acidosis in the brain may be the mechanism by which the drug exerts its antiseizure activity alternatively, the depolarizing action of bicarbonate ions moving out of neurons via GABA receptor ion channels may be diminished by carbonic anhydrase inhibition. Acetazolamide has been used for all types of seizures but is severely limited by the rapid development of tolerance, with return of seizures usually within a few weeks. The drug may have a special role in epileptic women who experience seizure exacerbations at the time of menses seizure control may be improved and tolerance may not develop because the drug is not administered continuously. The usual dosage is approximately 10 mg/kg/d to a maximum of 1000 mg/d. 

The furosemide extraction procedure was later examined for potential application in the analysis of thiazide diuretics in milk. Since this procedure could not provide sufficiently clean extracts for thiazides, additional acidic and basic extraction procedures were evaluated (557). Thus, milk was deproteinized with trichloroacetic acid, phosphoric acid, or potassium dihydrogen phosphate and centrifuged. The supernatants were extracted with ethyl acetate, evaporated to dryness, reconstituted in mobile phase, and analyzed by liquid chromatography. The recoveries in most cases were low and widely variable. Basic extraction, on the other hand, with sodium bicarbonate/potassium carbonate mixture or potassium monohydrogen phosphate followed by extraction with ethyl acetate also gave poor recoveries in most cases. It appears that a significant degradation of chlorothiazide occurred under the basic conditions. 

Thiazide diuretics act upon the kidneys to stimulate urine production. This can also result in excessive loss of sodium chloride, bicarbonate, and potassium ions. It is common practice to increase supplemental potassium intake during Thiazide use. Normal reference ranges for potassium are ... 

Other drugs may increase the effects of dextroamphetamine. For example, bicarbonate and other alkalin-izing agents increase the amount of amphetamines absorbed in the digestive system. Thiazides (potassium-depleting diuretics) decrease the amount of amphetamines that leave the body in urine. Also, other central nervous system stimulants, such as cocaine and nicotine, can amplify the stimulating effects of dextroamphetamines. 

Of the various solutes reabsorbed in the proximal tubule, the most relevant to diuretic action are sodium bicarbonate and sodium chloride. Of the currently available diuretics, only one group (carbonic anhydrase inhibitors, which block NaHC03 reabsorption) acts predominantly in the proximal tubule. In view of the large quantity of sodium chloride absorbed in the proximal tubule, a drug that specifically blocked reabsorption of this salt at this site might be a particularly powerful diuretic agent. No such drug is currently available. 

Inhibition of carbonic anhydrase activity profoundly depresses bicarbonate reabsorption in the proximal tubule. At its maximal safely administered dosage, 85% of the bicarbonate reabsorptive capacity of the superficial proximal tubule is inhibited. Some bicarbonate can still be absorbed at other nephron sites by carbonic anhydrase-independent mechanisms, and the overall effect of maximal acetazolamide dosage is about 45% inhibition of whole kidney bicarbonate reabsorption. Nevertheless, carbonic anhydrase inhibition causes significant bicarbonate losses and hyperchloremic metabolic acidosis. Because of this and the fact that HCO3" depletion leads to enhanced NaCl reabsorption by the remainder of the nephron, the diuretic efficacy of acetazolamide decreases significantly with use over several days. 

Acidosis predictably results from chronic reduction of body bicarbonate stores by carbonic anhydrase inhibitors and limits the diuretic efficacy of these drugs to 2 or 3 days. 

Carbonic anhydrase inhibitors, such as acetazolamide and dichlor-phenamide, act as diuretics to increase excretion of water by inhibiting carbonic anhydrase activity. This in turn leads to a reduction in the level of bicarbonate in aqueous humour. 

Stokke ES, Ostensen J, Hartmann A, Kiil F. Loop diuretics reduce lithium reabsorption without affecting bicarbonate and phosphate reabsorption. Acta Physiol Scand 1990 140(l) lll-8. 

Acetazolamide, dichlorphenamide, methazolamide and ethoxzolamide facilitate the excretion of hydrogen ions and the recovery of bicarbonate, They are never used as diuretics but are employed to reduce the production of aqueous humour in they eye (in glaucoma). 

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