Metabolic acidosis diuretics causing

The use of CA inhibitors as diuretics is limited by their propensity to cause metabolic acidosis and hypokalemia. Their use can be indicated in patients with metabolic alkalosis and secondary hyperaldosteronism resulting for example from aggressive use of loop diuretics. Furthermore, CA inhibitors are effective dtugs to produce a relatively alkaline urine for the treatment of cysteine and uric acid stones as well as for the accelerated excretion of salicylates. Perhaps the most common use of CA inhibitors is in the treatment of glaucoma. 

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. 

Carbonic anhydrase inhibitors were the forerunners of modern diuretics. They were discovered when it was found that bacteriostatic sulfonamides caused an alkaline diuresis and hyperchloremic metabolic acidosis. With the development of newer agents, carbonic anhydrase inhibitors are now rarely used as diuretics, but they still have several specific applications that are discussed below. The prototypical carbonic anhydrase inhibitor is acetazolamide. 

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. 

Around 60-70% of the filtered sodium is usually reabsorbed in the proximal tubule therefore, acetazolamide could be expected to have a rather potent diuretic effect. However, it produces rather modest diuresis because most of the excess sodium leaving the proximal tubule can be reabsorbed in the more distal segments of the nephron. Furthermore, its diuretic action is progressively diminished by the development of hyperchloremic metabolic acidosis caused by the loss of bicarbonate ions into the urine (Martinez-Maldonado Cordova 1990, Rose 1989, 1991, Wilcox 1991). In humans, the primary indication for acetazolamide (as a diuretic agent) is the treatment of edema with metabolic alkalosis. 

In addition to CKD as a risk factor, other contributing factors should also be considered. This includes exposure to potassium-sparing diuretics -blockers, which work predominantly via 82-antagonistic effects to interfere with the extrarenal translocation of potassium into cells and ACEls, which may cause hyperkalemia by reducing aldosterone production. Polycitra, used for the treatment of metabolic acidosis, contains potassium citrate and should not be prescribed for patients with severe CKD. If hyperkalemia develops, management options are based on the degree to which potassium is elevated (see Chap. 50). 

Whenever possible, potassium supplementation should be administered by mouth. Three salts are available for oral potassium supplementation chloride, phosphate, and bicarbonate. Potassium phosphate should be used when patients are both hypokalemic and hypophosphatemic potassium bicarbonate is most commonly used when potassium depletion occurs in the setting of metabolic acidosis. Potassium chloride, however, is the primary salt form used because it is the most effective treatment for the common causes of potassium depletion (i.e., diuretic-induced and diarrhea-induced hypokalemia). Because diarrhea and diuretics such as hydrochlorothiazide and furosemide promote net potassium and chloride losses, supplementation with potassium chloride repletes both electrolytes. Potassium chloride can be administered in either tablet or liquid formulations (Table 50-4). The liquid forms are generally less expensive however,... 

As with other K+-sparing diuretics, MR antagonists may cause life-threatening hyperkalemia. Indeed, hyperkalemia is the principal risk of MR antagonists. Therefore, these drugs are contraindicated in patients with hyperkalemia and in those at increased risk of developing hyperkalemia either because of disease or because of administration of other medications. MR antagonists also can induce metabolic acidosis in cirrhotic patients. 

B. Effects All three drugs in this class cause an increase in sodium clearance and a decrease in potassium and hydrogen ion excretion and therefore qualify as potassium-sparing diuretics. They may cause hyperkalemic metabolic acidosis (Table 15-2). 

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... 

This treatment causes a mild metabolic acidosis, due to impairment of renal reabsorption of bicarbonate. These agents are only moderately potent diuretics. Their diuretic effect is due to this impairment of bicarbonate reabsorption and as metabolic acidosis develops, the plasma bicarbonate concentration falls. The filtered load of bicarbonate therefore falls also and the diuresis is therefore poorly maintained. 

The combination of respiratory and metabolic alkalosis is the most common mixed acid-base disorder. This mixed disorder occurs frequently in critically ill surgical patients with respiratory alkalosis caused by mechanical ventilation, hypoxia, sepsis, hypotension, neurologic damage, pain, or drugs, and with metabolic alkalosis caused by vomiting or nasogastric suctioning and massive blood transfusions. It may also occur in patients with hepatic cirrhosis who hyperventilate, receive diuretics, or vomit, as well as in patients with chronic respiratory acidosis and an elevated plasma bicarbonate concentration... 

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