Howstuffworks "How Diuretics Work"

Diuretics are medicines that aid the elimination of sodium (salt) and water from the body. The oral forms of these drugs are sometimes referred to as "water pills." Diuretics act by increasing the excretion by the kidneys of sodium in the urine. When the kidneys excrete sodium, they excrete water from the blood along with it. That decreases the amount of fluid flowing through the blood vessels, which reduces pressure on the walls of the arteries.

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If you have high blood pressure or heart failure, your doctor may prescribe diuretics.

Diuretics are used to treat a number of conditions, including:

High blood pressure. Most patients with high blood pressure (hypertension) are effectively treated with diuretics. Patients taking a diuretic for high blood pressure will probably be advised to stick to a low-sodium diet. Diuretics act to lower blood pressure primarily by reducing blood volume; however, some diuretics can lower blood pressure in other ways and at lower doses than that required to produce increased urine output.
Heart failure. By flushing excess fluids from the body, diuretics can relieve the edema (swelling from excess fluids) that commonly occurs with heart failure. Most patients with heart failure are treated with diuretics in addition to a low-sodium diet. It's important for heart failure patients taking diuretics to have their salt (electrolyte) levels carefully monitored. Heart failure patients who are prescribed diuretics will often be on the medications for the rest of the lives.
Renal insufficiency. Diuretics are sometimes used to treat patients whose kidneys are unable to function normally, although they can also sometimes worsen this condition.
Liver disease. Diuretics can treat destruction and scarring of liver tissues when it is complicated by fluid buildup in the liver.
Hypercalcemia. Diuretics can treat excessive levels of calcium in the blood.
Diabetes insipidus. This disorder is marked by the excessive excretion of urine and persistent thirst. Some types of diuretics actually decrease urine volume in these patients.
Glaucoma. Some diuretics can be used to treat this eye disease, in which increased pressure within the eye causes damage and gradual loss of sight.
Cerebral edema. Some diuretics can treat potentially fatal brain swelling caused by hemorrhage, trauma, disease or surgery.
Polycystic ovarian syndrome (PCOS). A disorder marked by irregular menstruation, obesity, increased hair growth, cystic ovaries and infertility.

On the next page, we'll find out about the different kinds of diuretics.

Diuretic Types and Side Effects

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Most people with high blood pressure get relief from thiazide diuretics.

Each of the three main types of diuretic medicines works a little differently, but they all lower the amount of salt and water in the body, which helps to lower blood pressure. The choice of diuretic depends on the condition for which it is being prescribed. Urine flow usually increases within hours of the first dose, but diuretics may take several weeks to treat conditions like high blood pressure. The three main types of diuretics are:

Thiazide diuretics, which treat the vast majority of patients with high blood pressure and are the most commonly prescribed diuretic for heart patients. Thiazides increase urine excretion moderately and are the only type of diuretic that also acts to widen the blood vessels, which also helps to lower blood pressure.
Loop diuretics, which remove a large amount of sodium from the kidneys, produce the greatest increase in urine flow and are more powerful than thiazides. They are often used for patients with congestive heart failure and are also especially useful in emergencies. Although most commonly used as an oral medication, they may be administered intravenously in the hospital to treat patients with severe fluid overload.
Potassium-sparing diuretics, which don't have the side effect of lowering the body's potassium level, which is a problem with thiazide and loop diuretics. These are used frequently in congestive heart failure patients and are often prescribed in conjunction with the other two types of diuretics.

Side Effects of Diuretics
The most common side effect associated with diuretics is an increased elimination of potassium, resulting in a dangerously low level of potassium in the body. With the exception of potassium-sparing versions, all diuretics may cause a loss of potassium, which, if left untreated, increases the risk for heart rhythm disturbances that can be serious. Taking a potassium supplement or eating high-potassium foods (such as bananas and orange juice) may help maintain healthy potassium levels. A potential side effect of potassium-sparing diuretics is a dangerously high level of potassium in people who already have a high potassium level or who have kidney disease. Other potential side effects of diuretics include:

Frequent urination. Usually lasting for up to six hours, this is the most common side effect of diuretics.
Dehydration. Thirst, dry mouth, dizziness, constipation and dark-colored urine may result.
Cramps. Low potassium levels can cause cramps.
Dizziness and weakness. Older people may be particularly susceptible to this side effect, but it often resolves after taking the medication for a while.
Loss of appetite and vomiting. This side effect may also be related to low levels of potassium.

Generally, older patients may be more susceptible to side effects of diuretics and may require lower doses and close observation, but they are routinely prescribed these medications.

A good number of patients taking diuretics develop a resistance to them. We'll discuss diuretic resistance on the next page.

Diuretic Resistance

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Advil can decrease the effectiveness of diuretics.

Up to one in three heart-failure patients who take diuretic drugs experience diuretic resistance: when the process of eliminating excess sodium and water stops before enough fluid has been removed from the patient's body.

In patients with mild heart failure and good kidney function, diuretic resistance is uncommon. However, diuretic resistance occurs more often in patients with moderate or severe heart failure.

What conditions affect the effectiveness of diuretic drugs?

A diet high in sodium tends to counteract the effects of diuretics. Loop diuretics may work very well initially, but if the patient is consuming too much sodium, the kidney reabsorbs too much sodium.
Poor kidney function resulting in decreased blood flow to the kidneys can reduce the ability of loop diuretics to reach their target organ in the kidney.
Drug interactions can contribute to diuretic resistance. For instance, nonsteroidal anti-inflammatory drugs (NSAIDs) -- such as aspirin, ibuprofen (Advil^® or Motrin^®), or naproxen (Aleve^®) -- can decrease blood flow to the kidneys. Even small doses of aspirin may also interfere with sodium and water excretion and decrease the effectiveness of diuretic drugs.
Fluid overload in the stomach and intestines may reduce the absorption of oral diuretic drugs because they are absorbed in that area, so they may decrease diuretic effectiveness.
Physiological changes in heart failure, such as changes in absorption, distribution, metabolism and elimination of drugs, can affect the action of loop diuretic drugs; however, these effects alone do not fully explain diuretic resistance.

On the next page, we'll learn about how the body's response to diuretics can lead to resistance. We'll also find out how to treat diuretic resistance.

Treatment for Diuretic Resistance

The body responds to diuretic drug therapy in several different ways that can lead to diuretic resistance. Some of these responses cause the body to retain sodium and water in the short term (rebound), and some increase sodium and water retention in the long term (the braking phenomenon).

Short-term responses: The half-life of a diuretic drug in the bloodstream determines how often it must be administered. Since the half-life of most loop diuretics is on the order of hours, and they are sometimes administered only once a day, their effectiveness can be gone before the patient receives the next dose. When one dose has worn off, the kidneys may respond by aggressively retaining sodium. This rebound effect can last several hours and may even counteract the diuretic effect of the previous dose.

The action of a diuretic drug to increase the elimination of sodium in one segment of the kidney may result in the delivery of an increased load of sodium to downstream portions of the kidney, which then increases sodium reabsorption.

Long-term responses: The effectiveness of loop diuretics may decline over time during their long-term administration, as the body slowly adapts to their effects. This complex process, called the "braking phenomenon," is due to changes in the structure and function of the kidney itself, activation of the sympathetic nervous system and changes in several hormone pathways. These are all ways that the body tries to counteract the effect of the loop diuretic.

Changes in structure and function of the kidney can occur in the portion downstream from the segment where loop diuretics act. These changes, caused by increased delivery of sodium in this area over a period of time, can result in decreased effectiveness of diuretics.

When treating diuretic resistance, it's important for the patient to restrict daily consumption of fluids, follow a low-sodium diet and avoid taking nonsteroidal anti-inflammatory drugs (NSAIDs).

Other approaches include changing the dose or the timing of diuretic therapy. Because of the short duration of loop diuretics, individual doses given at intervals can cause rebound sodium retention between doses. The continuous administration of loop diuretics by continuous infusion loop diuretic therapy may be more effective than individual doses -- this is an option for patients with moderate to severe heart failure.

Another way to overcome diuretic resistance is to use more than one type of diuretic (such as a combination of thiazide and loop diuretics), because different types of diuretic drugs act upon different parts of the kidney and their combination may produce an improved diuretic response. For many patients, however, despite these strategies, diuretics eventually stop working.

When diuretics fail to relieve the fluid overload, patients may receive a procedure known as ultrafiltration.

To learn more about diuretics, take a look at the links on the next page.

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