Diuretics - Thiazide, thiazide-like, loop, and potassium-sparing diuretics: Nursing pharmacology

Diuretics, also called water pills, are medications that act on the kidneys to increase diuresis, or the production of urine, to help excrete more water from the body. Therefore, they are generally used to treat hypertension, as well as edema caused by fluid overload conditions, such as heart failure and pulmonary edema, as well as renal diseases like nephrotic syndrome, and hepatic diseases like cirrhosis. Diuretics are most often administered orally, but some of them can also be administered intravenously.

Once administered, these diuretics act on the kidneys’ basic unit, the nephron, to induce electrolyte and water excretion.

Zooming into the nephron, it’s made up of a glomerulus, which filters the blood. The filtered content goes through the renal tubules, which have four parts: the proximal convoluted tubule; the U-shaped loop of Henle, with a thin descending, a thin ascending, and a thick ascending limb; the distal convoluted tubule; and the collecting duct, which drain the urine out of the kidneys.

Now, the main classes of diuretics include thiazide and thiazide-like diuretics, loop diuretics, and potassium sparing diuretics.

Okay, starting with thiazide diuretics and thiazide-like diuretics, which have a slightly different structure but act in the same way. Available thiazide diuretics include chlorothiazide and hydrochlorothiazide, while examples of thiazide-like diuretics are chlorthalidone and indapamide.

Now, once administered, thiazide and thiazide-like diuretics act on the distal convoluted tubule, which has a sodium-chloride transporter that reabsorbs one sodium and one chloride ion together from the tubule. Thiazide diuretics block this transporter, which inhibits the reabsorption of sodium and chloride ions. And since water follows sodium, there will be more water molecules in the lumen as well, so more urine is produced.

Now, thiazide and thiazide-like diuretics are the first-line treatment of hypertension. However, these medications can’t induce immediate or large volume diuresis. For this reason, they’re not typically used alone for fluid overload conditions, such as heart failure and pulmonary edema.

Now, as with any type of diuretic, side effects of thiazide and thiazide-like diuretics mainly manifest as dehydration and electrolytes imbalance.

First off, thiazide diuretics tend to cause more retention of calcium and uric acid, which can result in hypercalcemia and hyperuricemia. Thiazides can also cause hypomagnesemia, hypochloremia, hyponatremia, as well as hypokalemia, which can cause arrhythmia, muscle cramps, and weakness. And due to the increased excretion of these electrolytes, thiazides may lead to metabolic alkalosis. Finally, thiazides can tamper with the metabolism of glucose and fat, which may lead to hyperglycemia, hyperlipidemia, and an increase in serum cholesterol and LDL.

As far as the contraindications go, thiazide diuretics should be avoided in clients with conditions like gout, diabetes mellitus, and hyperlipidemia. Thiazides are also contraindicated in clients who have renal failure with anuria. Finally, thiazides are sulfa medications, so they’re contraindicated in clients with sulfa allergy.

Next, we have loop diuretics, such as furosemide, torsemide, bumetanide, and ethacrynic acid. As the name suggests, loop diuretics act on the loop of Henle.

To be more specific, they mainly target the thick ascending limb, which has sodium-potassium-chloride cotransporters that normally reabsorb 30% of the filtered sodium, potassium, and chloride. Now, loop diuretics block these transporters, so these ions end up being excreted, and water follows them passively later across the collecting duct.

Because loop diuretics cause the excretion of a large amount of the filtered sodium in urine, their diuretic effect is almost three times greater than thiazide diuretics. For this reason, loop diuretics are typically used to treat conditions that need a rapid and large diuresis, such as heart failure and pulmonary edema. Now, in terms of side effects, loop diuretics can also cause dehydration and electrolyte imbalance, such as hypocalcemia and hypomagnesemia, as well as hypochloremia, hyponatremia and hypokalemia. And due to the increased excretion of these electrolytes, loop diuretics may lead to metabolic alkalosis. Other side effects are hypotension due to their strong diuretic effect, as well as ototoxicity, which can result in hearing impairment and tinnitus, especially when combined with other ototoxic medications like aminoglycosides. Finally, loop diuretics can tamper with the metabolism of glucose, which may lead to hyperglycemia.

Loop diuretics should not be given to clients who already present with electrolyte imbalance, severe renal failure with anuria, as well as in hepatic encephalopathy, which could be exacerbated by dehydration. In addition, loop diuretics should be avoided in clients with sulfa allergy, and should not be combined with other ototoxic medications. Finally, loop diuretics should be used with caution in clients with diabetes mellitus.

Alright, moving on to potassium sparing diuretics, which act on the distal convoluted tubules and the collecting tubules. These tubules have ATP-dependent potassium pumps that secrete potassium into the lumen to be excreted in urine, as well as hydrogen pumps that secrete hydrogen into the urine, and epithelial sodium channel pumps, or ENaCs, which reabsorb sodium. Now, the secretion and reabsorption of these ions in the distal convoluted and collecting tubules are regulated by the mineralocorticoid hormone aldosterone, which induces the synthesis of these pumps.

Now, there are two types of potassium sparing diuretics according to their mechanism of action. On the one hand, we’ve got those that directly inhibit the aldosterone receptor, like spironolactone and eplerenone. These medications can also be used to treat hyperaldosteronism, a condition where the adrenal gland produces excess aldosterone.