What is a Diuretic you ask...
Diuretics, sometimes commonly referred to as "water pills", are drugs that increase the rate of urine flow. In general, they increase the rate of sodium excretion from the body. Many people notice that eating salty foods causes them to retain fluids. They may notice that their eyes are puffy or their ankles are swollen. Salt is sodium chloride. Sodium is the main determinant of the water volume outside of the cells (referred to as the extracellular water). A diuretic that causes sodium to be lost in the urine decreases the volume of the extracellular water.

When excess fluid accumulates in tissues or body cavities, problems can occur. For example, excess fluid that collects in the air sacs and tissues of the lungs (referred to as pulmonary edema) interferes with the ability of the lungs to provide adequate respiration and can be life-threatening. Other diseases associated with excess fluid accumulation include congestive heart failure, cirrhosis of the liver and the nephrotic syndrome. Diuretics are frequently used in the treatment of these diseases. The most common use of diuretics is in the treatment of high blood pressure (hypertension). Initially, diuretics lower blood pressure by causing a decrease in the extracellular fluid volume and decreased output of blood by the heart (cardiac output). The long term effect is due to reduction in the resistance of vessels to blood flow which results in lower blood pressure.

Large amounts of sodium are filtered from the blood into the nephron which must then reabsorb most of it back into the body. There are multiple portions of the nephron where sodium reabsorption occurs. Diuretics from five main classes act on different sections of the nephron, giving these drugs their unique qualities. For example, some are much more potent than others (cause more sodium and water to be eliminated), some are more likely to cause potassium to be lost from the body, and some cause potassium to be retained by the body. In addition to having the same actions, diuretics acting at the same site in the kidney tend to have the same side effects and sometimes the same drug interactions. Therefore, they will be described according to the group to which they belong.  

Before we go on, I should clarify one thing.  Diuretics can be a serious danger to anyone if not prescribed and closely supervised by a medical professional.  That typically means an actually practicing Medical Doctor.  Not a personal trainer, or friend, or your personal guru that seems to know a lot about this kind of stuff.  I have watched bodybuilding and fitness competitors literally fall face down on the floor and be carried out on stretchers from misuse and outright abuse of diuretics.  This is a terrible weight loss tool and offers very little positive long term effect on fat loss.  The risks of prescription diuretics far out weigh the gains.  You can die from misuse of diuretics!  You will find that other more mild substances such as caffeine produce a diuretic effect.  Typically this effect is moderate enough to avoid any immediate negative health consequences.

Carbonic Anhydrase Inhibitors
Examples: Acetazolamide (Diamox®, Lederle Pharmaceuticals), methazolamide (Neptazane®, Lederle Pharmaceuticals), dorzolamide eye drops (Trusopt®, Merck and Co.) and others.

Carbonic anhydrase (CA) is an enzyme that exists in many places in the body including cells of the earliest part of the nephron, the proximal tubule. It is involved in the reversible reaction of combining carbon dioxide (the end product of respiration) and water to form a proton and bicarbonate. In the kidneys, sodium bicarbonate and water are resorbed in exhange, leaving hydrogen and chloride ions in the tubule. By blocking the action of this enzyme, more sodium and bicarbonate are eliminated in the urine. The net result is a mild diuretic effect and a mild excess of acid in the blood (acidosis) due to the loss of basic bicarbonate.

These drugs are rarely used for their diuretic activity. They are commonly used to treat glaucoma and high blood pressure in the eye. CA is involved in forming certain ocular fluids, and by inhibiting the enzyme, the production of this fluid decreases along with the pressure in the eye. The CA inhibitors are also used to prevent or treat mountain (altitude) sickness, a condition associated with reduced oxygen pressure at high altitudes that can occur in hikers making rapid ascents to high altitudes. Common symptoms include headache, shortness of breath, sleep disturbances, and nausea. In more serious cases, emergency treatment of life-threatening conditions associated with fluid accumulation in the brain and lungs is required.

Side effects with this type of diuretic are numbness, tingling, or burning in the hands, fingers, feet, toes, and mouth. Potassium deficiency can occur at high doses or when used simultaneously with other drugs that can cause potassium loss. It infrequently causes elevated blood sugar in diabetics. These drugs are chemically classified as sulfonamide derivatives, and infrequently cause sulfa allergies. Other, less common side effects can occur.

Loop Diuretics

Examples: furosemide (Lasix®, Lederle Pharmaceuticals), bumetanide
Bumex®, Hoffman La Roche), torsemide (Demadex®, Boehringer Mannheim), and ethacryinic acid (Edecrin®, Merck and Co.)

The portion of the nephron at which the most potent diuretics act is called the Loop of Henle. A certain "pump" in cells of the loop removes sodium along with potassium and chloride from the forming urine and transports it back into the bloodstream. The loop diuretics inhibit this pump, causing increased elimination of sodium (taking water with it) in the urine.

The loop diuretics are used to treat the excess fluid accumulation (edema) associated with congestive heart failure, cirrhosis of the liver, and certain kidney diseases. They are occasionally used to treat mild to moderate high blood pressure, although other types of diuretics are more frequently used for this condition. However, they are often used as part of the therapy in severe cases of high blood pressure and in acute pulmonary edema where fluid accumulating around the lungs interferes with the ability of the lungs to provide oxygen for the body. Due to the ability of these drugs to increase calcium excretion, they are occasionally used to treat elevated calcium levels, such as that which occurs in cancer of the bones.

The large amount of urine produced, particularly early in treatment, can be associated with dehydration and low blood pressure. In addition to increasing sodium elimination in the urine, the loop diuretics also increase the excretion of potassium, calcium, magnesium, bicarbonate, ammonium, and phosphate. Symptoms associated with these losses include mental confusion, weakness, dizziness, muscle cramps, headache, tingling in the hands and feet, thirst, nausea, and vomiting. They must be used cautiously in combination with other drugs that can cause hearing impairment or kidney damage.

Occasionally loop diuretics cause elevated blood sugar in diabetics. They can elevate cholesterol and triglycerides, although the long-term clinical significance of this effect is uncertain. Simultaneous use of nonsteroidal antiinflammatory agents (NSAIDS) may decrease the effect of the loop diuretics. Multiple other side effects and drug interactions are possible with these drugs.

All of the loop diuretics except ethacrynic acid are sulfonamides and can infrequently cause sulfa allergies. It is possible that people with an allergy to sulfa antibiotics such as sulfamethoxazole or sulfisoxazole will have cross-sensitivity to these diuretics.

Thiazide Diuretics

Examples: hydrochlorothiazide (HCTZ, available from many sources), chlorothiazide (Diuril®, Merck and Co.), methyclothiazide (Enduron®, Abbott Labs; Aquatensen®, Wallace Labs), bendroflumethiazide (Naturetin®, Squibb and Sons), and many others. Thiazides are also available in combination with other drugs that lower blood pressure.

Thiazides are commonly used as an initial treatment of high blood pressures. They are used in the treatment of conditions associated with excess fluid accumulation including congestive heart failure, however they are less potent than the loop diuretics (see above) that are more frequently used for these conditions. They are sometimes used to decrease swelling and fluid retention associated with premenstrual syndrome, and corticosteroid or estrogen therapy.

Thiazide diuretics may be used to treat diabetes insipidus, sometimes referred to as water diabetes. In one form of this rare disease, the kidney fails to respond to antidiuretic hormone (ADH, vasopressin) that signals the need for reabsorbing water back into the bloodstream rather than excreting it in the urine. As a result, large amounts of urine are formed. If inadequate fluids are consumed, the loss of excess water may cause dehydration and high blood sodium. The thiazides reduce urine volume primarily by reducing extracellular fluid volume and increasing water reabsorption at early portions of the nephron.

The main action of thiazides is thought to be inhibition of a protein that transports sodium chloride in the distal nephron, which results in an increased loss of sodium, chloride and water in the urine. Thiazides can also cause increased potassium and magnesium loss and decreased calcium loss in the urine. Potassium deficiency can cause abnormal heart rhythms (arrhythmias), which can have serious consequences. Potassium supplements may be given to correct the deficiency. Other signs of electrolyte (mainly sodium, potassium, chloride) imbalances include mental confusion, fatigue, faintness, dizziness, muscle cramps, headache, tingling in the hands and feet, thirst, nausea, and vomiting. The ability to decrease calcium excretion has caused these drugs to be used in patients with a tendency to form calcium containing kidney stones.

Thiazide diuretics can cause elevated blood sugar in diabetics. There may be cross-sensitivity between people with allergies to sulfa antibiotics and the thiazide diuretics. Thiazides can decrease excretion of uric acid by the kidney and may precipitate a gout attack in patients with this disease. The ability to decrease potassium levels is increased by simultaneous use of other drugs that can cause potassium loss including corticosteroids. Thiazides may increase sensitivity to the sun in certain people, therefore a sunscreen is recommended. Simultaneous use with nonsteroidal antiinflammatory drugs (NSAIDs) may result in a blunted diuretic effect.

Osmotic Diuretics

Examples include mannitol (Osmitrol®, Baxter Healthcare Corp.and others), glycerin (Osmoglyn®, Alcon Labs), isosorbide (Ismotic®, Alcon Labs)

Osmotic diuretics are generally used in a hospital setting. Osmotic substances have the ability to draw water out of tissues into the blood which can then be filtered by the kidneys and eliminated as urine. Mannitol, which is administered intravenously, is used to reduce excess fluid accumulation or pressure particularly in the head, and to increase urine flow in certain types of kidney failure or in the presence of drugs that have a potential to harm the kidneys. Mannitol is also used to increase urinary excretion of toxins or drugs in overdose cases. Some osmotic agents are given orally (isosorbide, glycerin) or as eye drops (glycerin) to reduce pressure in the eye associated with narrow-angle glaucoma or before eye surgery, as well as during eye examinations in the presence of corneal edema.

Potassium-Sparing Diuretics

There are two classes of potassium-sparing diuretics that act at distal portions of the nephron: those that block the sodium channel, and spironolactone, which inhibits aldosterone.

Sodium channel blockers
Examples include amiloride (Midamor®, Merck and Co., and generics), and triamterene (Dyrenium®, SmithKline Beecham)

Amiloride and triamterene act by blocking a sodium channel in the later portions of the nephron, the distal tubule and collecting duct. It is at this region of the nephron that potassium can be removed from the blood, secreted into the forming urine and subsequently eliminated. This is therefore an important site for potassium levels in the body to be controlled. By interfering with the passage of sodium through this channel, secretion of potassium into the urine from the bloodstream is inhibited and potassium is retained in the body. In addition, increased urinary excretion of sodium, bicarbonate, calcium, and water cause a slight diuretic effect.

These drugs are mainly used to treat or prevent low potassium associated with use of the other diuretics. They may be used in the as part of the treatment of conditions associated with excess fluid accumulation (edema), such as congestive heart failure and in the treatment of high blood pressure. Although they have much lower potency as diuretics than the other drugs described above, they may supplement their effects if used simultaneously. They are also useful in patients who cannot tolerate oral potassium supplements.

Because of their ability to increase potassium levels in the blood, other forms of potassium supplements are not used. Patients should discuss the use of potassium containing salt substitutes with their physician before using these products. Nonsteroidal antiinflammatory drugs (NSAIDs) have been associated with elevated potassium levels. In addition, NSAIDs may blunt the diuretic effects of these drugs. Signs and symptoms of high potassium levels include muscle weakness, abnormal sensation of prickling, numbness, or itching of the skin, commonly referred to as "pins and needles", fatigue, paralysis of the arms and legs, slow heart beat and shock.

Spironolactone (Aldactone®, Searle and Co., and others). Spironolactone is also available in combination with various thiazide diuretics

Spironolactone binds to the aldosterone receptor in the late distal tubules and collecting duct, thereby preventing the binding of aldosterone to its receptor and its subsequent effects. Aldosterone is a steroid hormone produced in the adrenal cortex that acts at the kidney to cause sodium (and water) retention and potassium loss in the urine. It is referred to as a mineralocorticoid. Spironolactone is frequently used to counter the effects of elevated aldosterone that occurs in edematous conditions such as heart failure, cirrhosis of the liver and the nephritic syndrome. Although excess fluid is present in these conditions, the accumulation of fluid in abnormal places such as the abdominal cavity or around the lungs, is associated with a low blood volume. The kidneys sense this deficit and signal the need for fluid retention, which ends up worsening the edematous condition. Spironolactone is a weak diuretic in comparison to thiazide or loop diuretics, but it may supplement the effects of thiazide diuretics.

Spironolactone is similar in structure to steroid compounds and can produce some of the adverse effects associated with steroids. In men, it may cause breast enlargement (gynecomastia), libido decrease, and impotence. Women may develop menstrual irregularities, postmenopausal bleeding, and breast tenderness. These effects are generally reversible following discontinuation of therapy. The potential to develop abnormally elevated potassium levels is similar to that associated with the other potassium-sparing diuretics (see above