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What are diuretics and how do they work?

The amount of fluid (water) retained by the body is controlled primarily by the kidneys. This occurs due to the kidney's ability to control the retention and elimination of sodium and chloride, because the amounts of sodium, chloride, and water in the body are carefully balanced. Thus, if sodium and chloride are eliminated from the body, water also is eliminated. Conversely, if sodium and chloride are retained by the body, so is water.

The elimination of sodium, chloride, and water from the body is somewhat complex. In the kidneys, sodium, chloride, and other small molecules are filtered out of the blood and into the tubules of the kidney where urine is formed. Most of the sodium, chloride, and water are reabsorbed into the blood before the filtered fluid leaves the kidney in the form of urine. To make matters even more complex, there are different mechanisms that are active in different parts of the tubules that affect the reabsorption of sodium and chloride.

Diuretics are a class of drugs that increase the flow of urine (termed diuresis). Diuretics work by removing sodium and chloride from the body in the urine, and the sodium and chloride in turn draw excess water from the body. The amount of sodium and chloride (sodium chloride, or NaCl) in the body, as previously discussed, has a marked effect on the amount of water retained by the body; hence most diuretics have their effects by reducing total-body sodium chloride content.

It is important to note that there is a delicate balance between dietary sodium intake and sodium loss. If the balance is compromised and there is a greater intake of sodium into the body but not enough removal of sodium, complications of fluid overload may occur, such as edema, pulmonary edema, or high blood pressure. When there is greater removal of sodium, but not enough intake of sodium, complications of fluid depletion may occur such as renal failure or reduced output of blood from the heart.

Continued use of diuretics, will cause some overall sodium and chloride loss. The body, however, has a natural way of compensating for these losses by reducing the excretion of sodium and chloride and stabilizing the amount of sodium, chloride and water in the body. In this manner, fluid depletion usually is prevented.

For what conditions are diuretics used?

Diuretics are used with other types of medications (adjunctive therapy) in edema associated with congestive heart failure (CHF), cirrhosis of the liver, and corticosteroid and estrogen therapy.

Diuretics also are useful in edema caused by renal dysfunction (for example, nephrotic syndrome, acute glomerulonephritis, and chronic renal failure). Diuretics are used to lower urinary calcium excretion, making them useful in preventing calcium-containing kidney stones.

Diuretics are used as the sole therapeutic agents to treat hypertension. Diuretics can also be used in combination with other antihypertensive drugs to treat more severe forms of hypertension.

Diuretics (specifically the carbonic anhydrase inhibitors) are used as adjunctive treatment of chronic simple (open-angle) glaucoma and secondary glaucoma

Thiazide diuretics have off–label (non-FDA-approved) uses for osteoporosis in postmenopausal women. They can be given alone or in combination with calcium or estrogen. Thiazide diuretics also have off-label uses for treating diabetes insipidus.

Are there differences among diuretics?

A major difference among diuretics is the level of potency. Potency variation is due to the differences in the sites of action of diuretics on the kidney structure.

Loop diuretics are the most potent diuretics as they increase the elimination of sodium and chloride by primarily preventing reabsorption of sodium and chloride. The high efficacy of loop diuretics is due to the unique site of action involving the loop of Henle (a portion of the renal tubule) in the kidneys.

Thiazide diuretics increase the elimination of sodium and chloride in approximately equivalent amounts. They do this by inhibiting the reabsorption of sodium and chloride in the distal convoluted tubules in the kidneys.

In the distal tubule, potassium is excreted into the forming urine coupled with the reabsorption of sodium. Potassium-sparing diuretics reduce sodium reabsorption at the distal tubule, thus decreasing potassium secretion. Potassium-sparing diuretics when used alone are rather weak, hence they are used most commonly in combination therapy with thiazide and loop diuretics.

Carbonic anhydrase inhibitors work by increasing the excretion of sodium, potassium, bicarbonate and water from the renal tubules

Osmotic diuretics are low-molecular-weight substances that are filtered out of the blood and into the tubules where they are present in high concentrations. They work by preventing the reabsorption of water, sodium and chloride.

What are side effects of diuretics?

When individuals present with fluid imbalance (depletion) due to diuretics, adverse events such as:

Extremely low levels of sodium caused by thiazide diuretics have been associated with death and neurologic damage in elderly patients.

Thiazide diuretics are associated with increase uric acid levels which may cause gout.

What are the drug interactions of diuretics?

Thiazide diuretics given concurrently with antidiabetic drugs [such as oral agents and insulin Apidra, Exubera, Humulin 70-30, Humalog Mix 50-50, Humalog 75-25, Humulin R, Humulin N, Humulin 50-50, Velosulin, Humalog, Lantus, Levemir, Novolog, Novolog Mix 50/50, Novolog Mix 70/30)] causes a decreased blood level of antidiabetic drugs, hence doses of antidiabetic drugs may need to be increased.

Among patients taking digoxin (Lanoxin), low levels of potassium caused by concurrent digoxin and diuretics (thiazide & loop diuretics) may cause weakness, cramps, and irregular heartbeats.

Lithium (Eskalith, Lithobid, Lithonate, Lithotabs) given concurrently with diuretics (thiazides and loop diuretics) may induce lithium toxicity due to decreased renal elimination of lithium. Lithium levels should be monitored to ensure safety.

Potassium-sparing diuretics given with angiotensin converting enzyme (ACE) inhibitors or nonsteroidal anti-inflammatory drugs (NSAIDs) [for example, indomethacin (Indocin)] have been associated with severely elevated levels of potassium (hyperkalemia). Severe hyperkalemia may present as muscle weakness, fatigue and slow heart rate (bradycardia). It is important to monitor potassium blood levels and to have an electrocardiogram performed.

Diuretics are often prescribed with other medications for high blood pressure and heart disease. This may increase the effects of these medications, potentially causing electrolyte abnormalities (such as reduced levels of potassium).

Examples of diuretics

Thiazides diuretics

Loop diuretics

Potassium sparing diuretics

Carbonic anhydrase inhibitors

Osmotic diuretics

Nonprescription diuretics

  • Maximum Strength Aqua Ban
Reviewed on 4/25/2016

Reviewed by:
Tova Alladice, M.D.
American Board of Physical Medicine & Rehabilitation

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