The most important indications for the use of the loop diuretics include acute pulmonary edema and other edematous conditions. Many times the treatment of the fluid overload will also serve as an effective anti-hypertensive agent, especially in the presence of renal insufficiency. The use of loop diuretics in these conditions is discussed below in Clinical Pharmacology of Diuretic Agents. Other indications for loop diuretics include hypercalcemia, hyperkalemia, acute renal failure, and anion overdose.
A. Hyperkalemia
In mild hyperkalemia—or after acute management of severe hyperkalemia by other measures—loop diuretics can significantly enhance urinary excretion of K+. This response is enhanced by simultaneous NaCl and water administration.
B. Acute Renal Failure
Loop agents can increase the rate of urine flow and enhance K+ excretion in acute renal failure. However, they cannot prevent or shorten the duration of renal failure. Loop agents can actually worsen cast formation in myeloma and light-chain nephropathy because increased distal Cl− concentration enhances secretion of Tamm-Horsfall protein, which then aggregates with myeloma Bence Jones proteins.
C. Anion Overdose
Loop diuretics are useful in treating toxic ingestions of bromide, fluoride, and iodide, which are reabsorbed in the TAL. Saline solution must be administered to replace urinary losses of Na+ and to provide Cl−, so as to avoid extracellular fluid volume depletion.
A. Hypokalemic Metabolic Alkalosis
By inhibiting salt reabsorption in the TAL, loop diuretics increase Na+ delivery to the collecting duct. Increased Na+ delivery leads to increased secretion of K+ and H+ by the duct, causing hypokalemic metabolic alkalosis (Table 15–2). This toxicity is very common and is a function of the magnitude of the diuresis and can be reversed by K+ replacement and correction of hypovolemia. At least one study has found that potassium supplementation upon initiation of loop diuretics, irrespective of the serum potassium concentration, will improve survival.
B. Ototoxicity
Loop diuretics occasionally cause dose-related hearing loss that is usually reversible. It is most common in patients who have diminished renal function or who are also receiving other ototoxic agents such as aminoglycoside antibiotics.
C. Hyperuricemia
Loop diuretics can cause hyperuricemia and precipitate attacks of gout. This is caused by hypovolemia-associated enhancement of uric acid reabsorption in the proximal tubule. It may be prevented by using lower doses to avoid development of hypovolemia.
D. Hypomagnesemia
Magnesium depletion is a predictable consequence of the chronic use of loop agents and occurs most often in patients with dietary magnesium deficiency. It can be reversed by administration of oral magnesium preparations.
E. Allergic and Other Reactions
All loop diuretics, with the exception of ethacrynic acid, are sulfonamides. Therefore, skin rash, eosinophilia, and less often, interstitial nephritis are occasional adverse effects of these drugs. This toxicity usually resolves rapidly after drug withdrawal. Allergic reactions are much less common with ethacrynic acid.