What are diuretics?

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Prescription medications used to prevent passive reabsorption of water in the kidney unit (nephron), resulting in an increased urinary output.
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Indications and Procedures

The basic functional unit of the kidney is the nephron. It consists of four regions: glomerulus, proximal convoluted tubule, loop of Henle, and distal convoluted tubule. The purpose of the nephron is to filter waste products from the blood and excrete these products as urine. Blood filtering occurs in the glomerulus. In the adult, approximately 180 liters of filtrate is produced daily. The purpose of the other three segments of the nephron are to reabsorb the majority of water and electrolytes from the filtrate and return these items to circulation, leaving approximately 1.8 liters to be discarded as urine.

In certain disease states it becomes necessary to enhance urine production to relieve symptoms and prevent morbidity (illness) or mortality (death). Increased urine production can be accomplished by the administration of a category of drugs known as diuretics. Diuretics are prescription medications that work by blocking the reabsorption of solutes, especially salt (sodium) and water, which passively follows sodium. Thus, solutes and water are excreted from the body rather than being returned to circulation. Diuretics are prescribed for conditions such as high blood pressure (hypertension), heart failure, pulmonary edema, kidney (renal) failure, and liver (hepatic) failure or cirrhosis with accompanying fluid in the abdominal cavity (ascites). Diuresis results in a lower blood volume and reduces blood pressure and the work of the heart. By removing fluid from the lungs breathing is less labored. Diuretics also maintain urine production in shock states. This prevents acute renal failure. Removing abdominal fluid makes it easier to breathe and comfort of the individual is increased.

The care provider will prescribe diuretic therapy after examining a patient and obtaining supporting information such as blood pressure, radiological examinations, and laboratory tests. The patient’s lifestyle, preferences, and the cost of medications are considered in the decision to prescribe diuretics and which type of diuretics to prescribe.

Uses and Complications

There are four major types of diuretics: high-ceiling, thiazide, potassium-sparing, and osmotic diuretics. The most potent are high-ceiling agents (for example, furosemide). These drugs are commonly referred to as loop diuretics because they exert effects on the loop of Henle portion of the nephron. Administration of loop diuretics may result in profound fluid and electrolyte loss. This can lead to serious side effects such as low blood volume (hypovolemia), low blood pressure (hypotension), and electrolyte and acid-base disturbances requiring treatment. Loop diuretics are ototoxic and can lead to hearing loss. Hearing loss may be reversed if reported to the care provider and the medication is stopped. An advantage of loop diuretics is that they continue to work even if renal blood flow is decreased. This is not true with other types of diuretics.

Another class of diuretic agents is the thiazides (for example, hydrochlorothiazide). Thiazides exert their effects on the proximal portion of the distal convoluted tubule. Although not as potent as high-ceiling diuretics they produce losses of electrolytes and water. Thiazide diuretics do not cause as much calcium excretion as loop diuretics and are useful in patients prone to calcium kidney stones. They suppress insulin production and glycogen storage resulting in higher blood glucose levels. This requires diabetic patients receiving thiazide diuretics to monitor blood glucose closely. Thiazides also decrease the excretion of uric acid. As uric acid blood levels rise, gout may develop. This class of diuretics is relatively inexpensive and well tolerated and is often used as first-line therapy for hypertension.

Potassium-sparing diuretics exert only a modest increase in urine output. There are two types of potassium-sparing agents: aldosterone antagonists (for example, spironalactone) and non-aldosterone antagonists (for example, amiloride). Aldosterone, a hormone secreted by the adrenal gland, increases sodium and water reabsorption in the nephron. By blocking aldosterone the reuptake of sodium and water is prohibited. Aldosterone antagonists require approximately forty-eight hours to demonstrate an effect. Non-aldosterone antagonists directly inhibit sodium and water reabsorption and effects begin without delay. Potassium-sparing diuretics cause minimal amounts of potassium to be lost in the urine. This class of diuretics is frequently used with loop or thiazide diuretics, not for diuresis, but to prevent potassium depletion. Side effects include too much potassium in the body (hyperkalemia) resulting in fatal heart rhythms, and endocrine effects. Because aldosterone antagonists are steroid hormones gynecomastia, menstrual irregularities, impotence, hirsutism, and deepening of the voice may occur. Potassium-sparing diuretics should not be taken with other drugs which are potassium sparing (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or direct renin inhibitors), potassium supplements, or salt substitutes containing potassium.

Osmotic diuretics are the final class of diuretic agents (for example, mannitol). Osmotic agents differ from other diuretic groups in their mechanism of action and indications for use. Osmotic drugs work by creating an osmotic force. When utilized to maintain urine production and prevent renal failure in patients suffering from shock, the drug is administered intravenously. In the kidney, the osmotic agent is freely filtered from the blood into the filtrate. It remains in the filtrate and holds water close to it in an attempt to maintain a normal solute-solvent ratio. The degree of diuresis is directly proportional to the concentration of osmotic agent in the filtrate. In treating increased pressure within the eye (intraocular pressure) as in glaucoma, osmotic eye drops work the same way—they create an osmotic force thus reducing pressure within the eye.

Diuretic drugs should be used with caution in patients with diabetes, gout, or renal impairment; during pregnancy; and when taking other drugs such as digoxin, lithium, ototoxic medications, nonsteroidal anti-inflammatory drugs (NSAIDs), or additional antihypertensive agents. Individuals should weigh daily in the morning before eating or drinking and keep a weight record that should be shared with the care provider. Also, they should check and record the blood pressure as instructed and remain alert to side effects of dehydration (dry mouth, thirst, low urine output), low potassium levels (irregular heartbeat, muscle weakness, cramping), or high potassium levels (slow or irregular heartbeat, high muscle tone, tingling).

Perspective and Prospects

Control of fluid and electrolytes to treat pathologic conditions such as hypertension, heart failure, pulmonary edema, and ascites is not new. Historical references go back to ancient Egypt. Throughout the centuries various medications to control these pathologies have been utilized including plants and herbs, and in the 1940s, mercury compounds. Thiazide diuretics were introduced in 1958 followed by the loop diuretic furosemide in 1966. Since that time additional diuretics have been invented. As the rate of obesity, type 2 diabetes mellitus, and hypertension continue to rise in the United States the need for diuretic agents will increase. Pharmaceutical companies consider new compounds that may show benefit as the next diuretic agent.


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