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Angiotensin-Converting Enzyme Inhibitors


About diuretics

Diuretics are non-habit-forming medications that stimulate the kidneys to produce more urine, flushing excess fluids and minerals (e.g., sodium) from the body. They may be prescribed in conjunction with low-sodium diets and other lifestyle changes. The most common diuretic medications fall into four major categories: loop, osmotic, potassium-sparing and thiazide (or thiazide-like).

  • Loop diuretics decrease the kidney’s ability to absorb sodium, causing more sodium to be eliminated through urine. Loop diuretics produce the greatest increase in urine flow. They may be administered through an intravenous (I.V.) line in the hospital to reduce swelling (edema) in patients with a variety of conditions (e.g., heart failure). They are most commonly used as oral medications.
  • Thiazide (or thiazide-like) diuretics increase the excretion of both sodium and chloride into the urine. They are commonly prescribed for heart patients, either alone or in conjunction with a potassium-sparing version. They are also commonly used to treat high pressure blood (hypertension). These drugs have been shown to reduce calcium excretion, meaning they are attractive options for patients with kidney stones or osteoporosis.
  • Potassium-sparing diuretics are used to protect the body from excess potassium loss, which can occur with loop and thiazide diuretics. Far less potent, potassium-sparing diuretics are commonly used in conjunction with the other forms of diuretics. They are also frequently used in patients with liver disease and ascites (fluid build-up in the abdomen due to liver damage). In addition, they can be used to treat high blood pressure and low potassium levels.
  • Osmotic diuretics are the least used form of diuretics. They draw fluid from the cells of the brain and eyes, as well as increase the elimination of toxins introduced into the body (from legal or illegal drugs) through urine. The mechanic process involves the increase of osmotic pressure (ion concentration) in blood and blood vessels, inhibiting the reabsorption of water and dissolved substances, and causing an increase in urine flow.

Diuretics are generally taken orally in tablet, capsule or liquid form. They can also be administered through intravenous injection. Urine flow usually increases within hours of the first dose, but diuretics may take several weeks to treat conditions such as high blood pressure.

The increased urine flow flushes the following dissolved substances (solutes) from the body:

  • Sodium
  • Potassium (except for potassium-sparing diuretic)
  • Calcium
  • Magnesium
  • Chloride
  • Phosphorus
  • Uric acid

Stimulating the body to remove more of these solutes also rids the body of the water in which they are suspended.

Some specific types of diuretics include:

  • bumetanide
  • ethacrynic acid
  • furosemide
  • torsemide
  • glycerin
  • isosorbide
  • mannitol
  • urea
  • amiloride hydrochloride
  • spironolactone
  • triamterene
  • eplerenone
Thiazide (or thiazide-like)
  • bendroflumethiazide
  • benzthiazide
  • chlorothiazide
  • chlorthalidone
  • cyclothiazide
  • hydrochlorothiazide
  • flumethiazide
  • indapamide
  • methyclothiazide
  • metolazone
  • polythiazide
  • quinethazone
  • trichlormethiazide

Conditions treated

Thiazide diuretics are considered to be the front-line treatment for high blood pressure (hypertension). A recently concluded large-scale study recommended they be used before other blood-pressure-lowering medications. The study, known as the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial or ALLHAT, involved more than 42,000 people aged 55 and older across the United States, Canada, Puerto Rico and the U.S. Virgin Islands.

The ALLHAT study’s conclusion was based on the finding that most blood pressure medications were about equally effective (lowering blood pressure to normal levels in 30 to 50 percent of patients). Therefore, the decision on which medication to use is based on other factors, such as the drug’s potential for side effects and its cost. Diuretics are generally well tolerated and not very expensive. Another finding of the study was that, overall, most individuals need more than one drug to treat high blood pressure, and one of those drugs should be a diuretic.

The study has, however, generated great controversy within the medical community, partly because of the finding that patients in the diuretic group are more likely to develop diabetes. The long-term consequences of this were not addressed in the study.

In addition to high blood pressure, diuretics are used to treat the following conditions:

  • Heart failure. By flushing excess fluids from the body, diuretics can relieve the edema (swelling from excess fluids) that commonly occurs with heart failure. Specifically, spironolactone and eplerenone have been independently shown to benefit patients with heart failure, thus reducing the workload on the heart. Most patients with heart failure are treated with a loop diuretic, in addition to a low sodium diet. In addition, spironolactone or eplerenone may be added to increase the drug's effectiveness and reduce the loss of potassium often caused by diuretics. It is important for any patients taking diuretics for heart failure to have their 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. A condition in which the kidneys are unable to function normally. Diuretics can sometimes worsen this condition.
  • Hepatic cirrhosis. Destruction and scarring of liver tissues, when complicated by ascites (fluid build-up in the liver caused liver cirrhosis, heart failure or nephrotic syndrome).
  • Hypercalcemia. Too much calcium in the blood.
  • Diabetes insipidus (thiazide diuretics only). A pituitary gland disorder marked by excessive thirst and the excretion of large amounts of urine. Thiazide diuretics actually decrease urine volume in these patients.
  • Glaucoma (osmotic diuretics only). An eye disease in which increased pressure within the eye causes damage and gradual loss of sight.
  • Cerebral edema (osmotic diuretics only). A potentially fatal swelling in the brain that can be caused by hemorrhage, trauma, disease or surgery.
  • Drug intoxication (osmotic diuretics only). Osmotic diuretics increase the urinary excretion of toxins introduced into the body through the use of many legal and illegal substances.
  • Hyperaldosteronism (potassium-sparing diuretics only). A condition in which the increased production of the hormone aldosterone causes increased blood pressure, excessive potassium loss and muscle weakness.
  • Polycystic ovarian syndrome (PCOS). A disorder marked by irregular menstruation, obesity, increased hair growth, cystic ovaries and infertility.

Conditions of concern

Patients should use diuretics with caution if they have been diagnosed with any of the following conditions:

  • Diabetes. Careful blood sugar monitoring is required when diabetics take diuretics because they increase the risk of hyperglycemia (high blood sugar). However, diabetics are commonly prescribed diuretics if the benefit (e.g., treatment of high blood pressure or heart failure) outweighs the risk. The ALLHAT study also confirmed the value of diuretics among patients with diabetes.
  • Hyperlipidemia (for thiazide diuretics only). Excess fat (lipids) in the blood. At higher doses, thiazide diuretics are associated with elevations in cholesterol levels. Newer dosage regiments usually rely on lower doses of thiazide diuretics, which have reduced this problem.
  • Severe liver or kidney disease or a history of kidney stones. The effect of the diuretic may be increased because of the slow removal of the drug from the body by these organs.

In addition, diuretics may make some disorders worse. Patients with the following conditions should discuss the risks with their physicians:

  • Gout. A painful inflammation of the joint caused by an excessive amount of uric acid in the blood and deposits of urates in and around joints.
  • Hearing problems.
  • Pancreatitis. Inflammation of the pancreas.
  • Menstrual problems or breast enlargement (potassium-sparing diuretics only).

Some studies have also suggested that diuretic therapy may actually increase cardiovascular risk because of the medication’s effect on potassium, magnesium, cholesterol and blood glucose levels. However, this risk may be lessened by using low-dose diuretics.

Side effects

Potential side effects of diuretics

The most common side effect associated with diuretics is potassium loss. With the exception of potassium-sparing versions, all diuretics may cause a loss of potassium. Rarely, potassium-sparing diuretics can cause a build-up of potassium in the body. Symptoms of potassium loss include:

  • Tiredness
  • Weakness
  • Numbness
  • Tingling
  • Muscle cramps
  • Constipation
  • Vomiting
  • Fast heartbeat (tachyarrhythmia)

Patients should contact their physicians if they have any of the following side effects from diuretics, most of which are related to diuresis (urinating too much) and dehydration:

  • Dry mouth
  • Increased thirst
  • Arrhythmia (abnormal heartbeat)
  • Confusion, mental changes or moodiness
  • Weak pulse
  • Heaviness or weakness of the legs
  • Dizziness or lightheadedness, especially after getting up from a sitting or lying position

Less common side effects of diuretics may include:

  • Allergic reaction
  • Fainting (syncope)
  • Increased sensitivity to sunlight, causing severe sunburn or rash
  • Blurred vision
  • Confusion or nervousness
  • Diarrhea, stomach cramps or pain
  • Loss of appetite
  • Difficult or painful urination
  • Muscle twitches or spasms
  • Joint pain
  • Fever or chills
  • Erectile dysfunction (impotence) or decreased desire for sex
  • Headache or ringing in ears
  • Unusual bleeding or bruising
  • Jaundice (yellow tint to the skin or eyes)
  • Mood change
  • Weight changes

Rarely, potassium-sparing diuretics may produce breast enlargement in males and females, causes breast tenderness, deepening of the voice, increased hair growth, irregular menstrual periods and unusual sweating.

Patients on diuretics should inform their physicians if they become sick, especially with severe or continuing vomiting or diarrhea. These conditions can cause the body to lose too much water and potassium.


Drug or other interactions

Patients should consult their physicians before taking any additional prescriptions, over-the-counter medications or nutritional supplements. Other substances that can influence the effects of diuretics include:

  • Antihypertensives (drugs that slow heart rate or lower blood pressure) such as ACE inhibitors. Although commonly prescribed for diabetics, these can strengthen the effects of diuretics and potentially lead to low blood pressure (hypotension).
  • Psychiatric medications. Some diuretics can cause a build-up of these medications in the blood, increasing the chance of side effects.
  • Licorice. Eating certain types of licorice while taking diuretics may cause excessive potassium loss.

Alcohol use, exposure to heat and prolonged standing may also intensify the adverse effects of diuretics.


Lifestyle considerations

When first taking a diuretic, patients should avoid operating heavy machinery (e.g., driving) until they know how the medication will affect them. Some patients may experience fatigue when first taking this medication, but this usually passes after the patient has been on the medication for some time. Urine flow will increase and some patients may need to wake during the night to urinate. To minimize this, patients with a single daily dose should take their medication in the morning after breakfast. Patients taking more than one dose a day are advised to take their last dose before 6 p.m. In addition, some diuretics can increase the skin’s sensitivity to sunlight. Patients are advised to use sunscreen and avoid tanning booths. Furthermore, patients being treated for heart failure may need to weigh themselves frequently and report any loss or gain of more than 5 pounds in a week.

Patients should drink enough liquids during exercise or in hot weather and follow their physician’s instructions regarding exercise, activity levels and diet. Physicians may instruct patients to add foods high in potassium to their diets or prescribe a potassium supplement, but patients should not attempt to change their diets without direction from their physician. Extra potassium is not necessary for every patient on diuretics and too much potassium can be harmful. In addition, patients taking loop diuretics may be advised to take magnesium supplements in addition to potassium supplements, because the reabsorption of this solute is limited by the medication.

Most patients taking diuretics to treat high blood pressure (hypertension) will be using the medication for the rest of their lives, provided no serious side effects occur. Patients should remember that diuretics can help to control high blood pressure, but cannot cure it. Even if all their symptoms cease, patients should continue to take their medication exactly as directed and to keep all scheduled follow-up appointments with their physician.

How to use

Pregnancy use issues

Use of diuretics during pregnancy is not recommended. The effects of diuretics during pregnancy have not been studied extensively. However, it has been noted that diuretics given after the first trimester of pregnancy to treat hypertension may interfere with the normal expansion of fluid seen during pregnancy. The depletion of this fluid volume could, in turn, disrupt neurodevelopment of the fetus and increase the risk of conditions such as schizophrenia in the offspring. There is also a risk of jaundice, blood problems and potassium depletion in the newborn.

In lactating women, most diuretics will pass into breast milk and can cause dehydration in nursing infants. Potassium-sparing diuretics, however, have not been found to cause problems in nursing babies.

Child use issues

The use of diuretics in children is typically seen for the treatment of milder degrees of heart failure. There is no indication that the risk of side effects from diuretics is different in children than in adults. Dosages are lower for children and the dosage interval may be longer. Children taking potassium-sparing diuretics are more prone to developing calcium deficiencies than are adults. Safety of diuretic use in children has not been scientifically established for all forms of the medication. Parents are encouraged to discuss the potential risks and benefits with a board-certified pediatric cardiologist before their child begins taking diuretics.

Elderly use issues

Older adults have a higher frequency and intensity of side effects, such as lightheadedness, dizziness and fainting (syncope). They are also more susceptible to dehydration, hypovolemia (decrease in circulating blood volume), and deficiencies of calcium, potassium, sodium and magnesium. Generally, older patients require lower doses of diuretics and require close observation but are routinely prescribed these medications.

Symptoms of diuretic overdose

Patients exhibiting any of the following should contact their physician immediately:

  • Severe low blood pressure (hypotension)
  • A fast or irregular heartbeat (tachycardia)
  • Severe dizziness or fainting (syncope)
  • Deafness or ringing in the ears
  • Excessive thirst
  • Poor skin tension
  • Muscle cramps or weakness
  • Drowsiness
  • Weak pulse
  • Confusion
  • Excessive thirst
  • Cardiac arrest
  • Deep sleep or coma (prolonged unconsciousness)

Questions for your doctor

You may wish to ask your doctor the following questions about diuretics:
  1. Are diuretics safe for everyday use?
  2. Why am I specifically taking a diuretic?
  3. How will taking a diuretic help my condition?
  4. Are there any symptoms that might indicate my diuretic is not working properly?
  5. Should I drink more or less fluid when taking a diuretic?
  6. If I miss a dose, should I double my dose the next time?
  7. Do all diuretics deplete potassium?
  8. Should I add salt to my foods while taking diuretics?
  9. What is my target blood pressure?
  10. Which other drugs might I take to enhance the blood-pressure-lowering effect of diuretics?
  11. Are there are vitamins or supplements that might enhance the effectiveness of diuretics? Any that I should avoid?
  12. How often should I monitor my blood pressure?


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