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. 

The development of sulfonamide carbonic anhydrase inhibitors was based on the observation that antibacterial sulfanilamides produce alkaline urine. This discovery led to the development of acetazolamide (8.29), a thiadiazole derivative. It is not an ideal drug because it promotes K+ excretion and causes a very high urine pH. Since chloride ions are not excreted simultaneously, systemic acidosis also results. Much more useful are the chlorothiazide (8.30) derivatives, which are widely used as oral diuretic drugs. These compounds differ from one another mainly in the nature of the substituent on C3 ... 

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. 

By inhibiting H+ secretion in parallel with K+ secretion, the K+-sparing diuretics can cause acidosis similar to that seen with type IV renal tubular acidosis. 

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. 

Q10 Beta-adrenoceptor antagonists are contraindicated in patients with asthma or respiratory obstructive diseases, bradycardia, heart block or heart failure. Adrenergic agonists are contraindicated in patients with closed-angle glaucoma and should be used cautiously in patients with hypertension or heart disease. Parasympathomimetics cause poor night vision and dimming of vision, because of development of miosis, headache and brow ache. Carbonic anhydrase inhibitors have a weak diuretic action and can induce depression, drowsiness, paraesthesia, electrolyte disturbance such as hypokalaemia, acidosis and lack of appetite. 

The carbonic anhydrase inhibitors are the most kaliuretic of all diuretics and can cause severe hypokalemia during the first few days of administration. However, hypokalemia is not a problem during long-term administration, because of compensatory potassium retention secondary to acidosis (10). 

Acetazol- amide 125 mg t.i.d. 500 mg t.i.d. 90% 100% 50% Avoid May potentiate acidosis ineffective as diuretic in ESRD may cause neurologic side effects in dialysis patients No data No data Avoid... 

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. 

Secondary gout is a result of hyperuricemia attributable to several identifiable causes. Renal retention of uric acid may occur in acute or chronic kidney disease of any type or as a consequence of administration of drugs diuretics, in particular, are implicated in the latter instance. Organic acidemia caused by increased acetoacetic acid in diabetic ketoacidosis or by lactic acidosis may interfere with tubular secretion of urate. Increased nucleic acid turnover and a consequent increase in catabolism of purines may be encountered in rapid proliferation of tumor cells and in massive destruction of tumor cells on therapy with certain chemotherapeutic agents. 

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,... 

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... 

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. 

---