Diuretic

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This illustration shows where some types of diuretics act, and what they do.
A diuretic is any drug that elevates the rate of urination and thus provides a means of
forced diuresis. There are several categories of diuretics. All diuretics increase the
excretion of water from bodies, although each class does so in a distinct way.

Contents
[hide]

1 Types
o 1.1 High ceiling loop diuretics
o 1.2 Thiazides
o 1.3 Digitalis
o 1.4 Potassium-sparing diuretics
o 1.5 Calcium-sparing diuretics
o 1.6 Osmotic diuretics
o 1.7 Low ceiling diuretics
2 Uses
3 Mechanism of action
4 Adverse effects
5 See also
6 References
7 External links

[edit] Types
[edit] High ceiling loop diuretics
High ceiling diuretics are diuretics that may cause a substantial diuresis up to 20%[1]
of the filtered load of NaCl and water.This is huge when compared to normal renal
sodium reabsorption which leaves only ~0.4% of filtered sodium in the urine.
Loop diuretics have this ability, and are therefore often synonymous with high ceiling
diuretics. Loop diuretics, such as furosemide, inhibit the body's ability to reabsorb
sodium at the ascending loop in the kidney which leads to a retention of water in the
urine as water normally follows sodium back into the extracellular fluid (ECF). Other
examples of high ceiling loop diuretics include ethacrynic acid, torsemide and
bumetanide.

[edit] Thiazides
Thiazide-type diuretics such as hydrochlorothiazide act on the distal convoluted
tubule and inhibit the sodium-chloride symporter leading to a retention of water in the
urine, as water normally follows penetrating solutes. Frequent urination is due to the
increased loss of water that has not been retained from the body as a result of a
concomitant relationship with sodium loss from the convoluted tubule. The short-term
anti-hypertensive action is based on the fact that thiazides decrease preload,
decreasing blood pressure. On the other hand the long-term effect is due to an
unknown vasodilator effect that decreases blood pressure by decreasing resistance.

[edit] Digitalis
Digitalis has a diuretic effect on heart failure patients. [add more info]

[edit] Potassium-sparing diuretics

These are diuretics which do not promote the secretion of potassium into the urine;
thus, potassium is spared and not lost as much as in other diuretics. The term
"potassium-sparing" refers to an effect rather than a mechanism or location;
nonetheless, the term almost always refers to two specific classes that have their effect
at similar locations:

Aldosterone antagonists: spironolactone, which is a competitive antagonist of

aldosterone. Aldosterone normally adds sodium channels in the principal cells
of the collecting duct and late distal tubule of the nephron. Spironolactone
prevents aldosterone from entering the principal cells, preventing sodium
reabsorption. A similar agent is potassium canreonate.

Epithelial sodium channel blockers: amiloride and triamterene.

[edit] Calcium-sparing diuretics

The term "calcium-sparing diuretic" is sometimes used to identify agents that result in
a relatively low rate of excretion of calcium.[2]
The reduced concentration of calcium in the urine can lead to an increased rate of
calcium in serum. The sparing effect on calcium can be beneficial in hypocalcemia, or
unwanted in hypercalcemia.
The thiazides and potassium-sparing diuretics are considered to be calcium-sparing
diuretics.[3]

The thiazides cause a net decrease in calcium lost in urine.[4]

The potassium-sparing diuretics cause a net increase in calcium lost in urine,
but the increase is much smaller than the increase associated with other
diuretic classes.[4]

By contrast, loop diuretics promote a significant increase calcium excretion.[5] This

can increase risk of reduced bone density.[6]

[edit] Osmotic diuretics

Compounds such as mannitol are filtered in the glomerulus, but cannot be reabsorbed.
Their presence leads to an increase in the osmolarity of the filtrate. To maintain
osmotic balance, water is retained in the urine.
Glucose, like mannitol, is a sugar that can behave as an osmotic diuretic. Unlike
mannitol, glucose is commonly found in the blood. However, in certain conditions
such as diabetes mellitus, the concentration of glucose in the blood (hyperglycemia)
exceeds the maximum reabsorption capacity of the kidney. When this happens,
glucose remains in the filtrate, leading to the osmotic retention of water in the urine.
Glucosuria causes a loss of hypotonic water and Na+ leading to a hypertonic state with
signs of volume depletion such as: dry mucosa, hypotension, tachycardia, and
decreased turgor of the skin. Use of some drugs, especially stimulants may also
increase blood glucose and thus increase urination.

[edit] Low ceiling diuretics

The term "low ceiling diuretic" is used to indicate that a diuretic has a rapidly
flattening dose effect curve (in contrast to "high ceiling", where the relationship is
close to linear). It refers to a pharmacological profile, not a chemical structure.
However, there are certain classes of diuretic which usually fall into this category,
such as the thiazides.[7]

[edit] Uses
In medicine, diuretics are used to treat heart failure, liver cirrhosis, hypertension and
certain kidney diseases. Some diuretics, such as acetazolamide, help to make the urine
more alkaline and are helpful in increasing excretion of substances such as aspirin in
cases of overdose or poisoning. Diuretics are often abused by sufferers of eating
disorders, especially bulimics, in attempts at weight loss.
The antihypertensive actions of some diuretics (thiazides and loop diuretics in
particular) are independent of their diuretic effect. That is, the reduction in blood
pressure is not due to decreased blood volume resulting from increased urine
production, but occurs through other mechanisms and at lower doses than that
required to produce diuresis. Indapamide was specifically designed with this in mind,
and has a larger therapeutic window for hypertension (without pronounced diuresis)
than most other diuretics.

[edit] Mechanism of action

Classification of common diuretics and their mechanisms of action:

Examples

Mechanism

Location

(numbered in
distance along
nephron)

Ethanol, Water

1.

1.
inhibit
amphotericin B,
5. collecting
Arginine vasopressin
vasopressin's
lithium citrate
duct
receptor 2 antagonists
action
Increases blood
Goldenrod, Juniper
1.
Aquaretics
flow in kidneys
2. proximal
promote Na+
Na-H exchanger antagonists dopamine[8]
excretion
tubule[8]
inhibit H+
secretion,
2: proximal
Carbonic anhydrase inhibito acetazolamide[8],
resultant
dorzolamide
rs
+ tubule
promotion of Na
and K+ excretion
bumetanide[8],
3. medullary
ethacrynic acid[8], inhibit the Na-Kthick
Loop diuretics
furosemide[8],
2Cl symporter
ascending limb
torsemide
2. proximal
glucose (especially
promote osmotic tubule,
in uncontrolled
Osmotic diuretics
diuresis
descending
diabetes), mannitol
limb
inhibition of
Na+/K+
exchanger:
amiloride,
Spironolactone
spironolactone,
5. cortical
inhibits
collecting
Potassium-sparing diuretics triamterene,
aldosterone
potassium
ducts
action, Amiloride
canrenoate.
inhibits epithelial
sodium
channels[8]
inhibit
bendroflumethiazid
4. distal
reabsorption by
e,
convoluted
Thiazides
Na+/Clhydrochlorothiazide
tubules
symporter
inhibit
caffeine,
reabsorption of
theophylline,
Na+, increase
1. tubules
Xanthines
theobromine
glomerular
filtration rate
Acidifying salts

CaCl2, NH4Cl

inhibits
vasopressin
secretion

Chemically, diuretics are a diverse group of compounds that either stimulate or inhibit
various hormones that naturally occur in the body to regulate urine production by the
kidneys. Herbal medications are not inherently diuretics. They are more correctly
called aquaretics.

[edit] Adverse effects

The main adverse effects of diuretics are hypovolemia, hypokalemia, hyperkalemia,
hyponatremia, metabolic alkalosis, metabolic acidosis and hyperuricemia [8]. Each are
at risk of certain types of diuretics and present with different symptoms.
Adverse
Diuretics

effect

Symptoms
lassitude[8]
thirst[8]
muscle cramps[8]
hypotension[8]

loop diuretics
thiazides[8]

acetazolamides[8]
loop diuretics[8]
thiazides[8]

muscle weakness[8]
paralysis[8]
arrhythmia[8]

amilorides[8]
triamterenes[8]
spironolactone[8]

arrhythmia[8]
muscle cramps[8]
paralysis[8]

thiazides[8]
furosemides[8]

hyponatremia

CNS symptoms[8]
[8]
o coma

metabolic alkalosis

loop diuretics[8]
thiazides[8]

arrhythmia[8]
CNS symptoms[8]

Kussmaul respirations[8]
muscle weakness
neurological symptoms[8]
o lethargy
o coma
o seizures
o stupor

gout
tissue calcification[8]
fatigue
depression
confusion
anorexia
nausea

Hypovolemia

hypokalemia

Hyperkalemia

metabolic acidosis

hypercalcemia

[8]

acetazolamides[8]
amilorides[8]
triamterene[8]

thiazides[8]

hyperuricemia

thiazides[8]
loop diuretics[8]

vomiting
constipation
pancreatitis
increased urination

gout[8]