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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 re-absorption 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 reabsorbed
in exchange, 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
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