Diuretic drugs

Diuretic drugs




I-Overview

They are drugs inducing a state of increased urine flow
They are ion transport inhibitors that decrease the reabsorbtion of Na at different sites in the nephron

As a result,Na and other ions such as cl enter the urine in greater amounts than normal along with water which is carried passively to maintain osmotic equilibrium

II-Kidney function in disease
in many diseases,the amount of Nacl reabsorbed by the kidney tubules is abnormally high

this leads to the retention of water,an increase in blood volume,and expansion of the extravascular fluid compartment resulting in edema of the tissues

Several commonly encounterd causes of edema include

a- Congestive heart failure

the decreased ability of the failing heart to sustain adequate cardiac output,causes the kidney to respond as if there were a decrease in blood volume
The kidney as a part of normal compensatory mechanism retains more salt and water as a means of raising blood volume and increasing the amount of blood that it is returned to the heart
However,the diseased heart can not ingrease its cardiac output,and the increased vascular volume results in edema

b-Hepatic ascitis

Ascitis: the accumulation of fluid in abdominal cavity,is a common complication of cirrhosis of the liver
that is due to
The increased portal blood pressure
the secondary hyperaldosteronism

c-Nephrotic syndrome
d-Premenstural edema
is a result of imbalances in hormones such as estrogen exess which facilitates the loss of fluid into the extracellular space

A-Carbonic anhydrase inhibitors
e.g acetazolamide

Therapeutic uses

Treatment of glaucoma :by decreasing the production of aquous humor ,probably by blocking the carbonic anhydrase in the cilliary body of the eye
it is useful in the chronic treatment of glaucoma but should not be used for an acute attack

N.B. Pilocarpine is preferred in acute attack because of its immediate action

Epilepsy : it reduces the severity and magnitude of the seizures
often it is used chronically in conjunction with antiepileptic medication to enhance the action of these other drugs
Mountain sickness:less commonly it can be used in the prophylaxis of acute mountain sickness among healthy physically active individuals who rapidly ascend above 10000 feet

B-Loop diuretics
e.g bumetanide-furosemide

These drugs have the highest efficacy in mobilizing Na & cl from the body
Furosemide shows the greater side effects than those seen with the other loop diuretics
Bumetanide is much more potent and its use is increasing

Therapeutic uses
Drugs of choice for reducing the acute pulmonary edema of C.H.F because of their rapid onset of action
Useful in treatment hypercalcemia

Adverse effects

a-Ototoxicity :particullary when used in conjunction with aminoglucosides antibiotics

N.B. Permanent damage may result with continued treatment

b- hyperuricemia :especially furosemide causing or exacerbating gouty attacks

c- Acute hypovolemia:with possibility of hypotension,shock and cardiac arrythmias

d- Potassium depletion : which can be averted by use of potassium sparing diuretic or dietary supplementation with K

C-Thiazides and related agents
e.g: chlorthiazide - hydroghlorothiazide-indapamide

The most widely used of diuretic drugs
Chlorthiazide

Therapeutic uses

Hypertension =discussed
C.H.F = discussed
Renal impairment :if loop diuretics alone fail in treatment
Idiopathic hypercalciuria
Diabetes inspidus

Adverse effects
as loop diuretics plus
In hyperglycemia :patients with diabetes mellitus who are taking thiazides for hypertension may become hyperglycemic and have difficulty in maintaining appropiate blood sugar levels

Hydrochlorothiazide

is a thiazide derivative has proven to be more popular than the parent drug as it is more potent so less dose is required to provide the same efficacy of the parent drug

Indapamide = thiazide analoge
at low doses it

Shows significant antihypertensive action with minimal diuretic effects
Often used in advanced renal failure to stimulate additional diuresis on top of that achieved by loop diuretics

Less likely to accumulate in patients with renal failure and may be useful in their treatment

D-Potassium-sparing diuretics
e.g spironolactone

act in the collecting tubule to inhibit Na reabsorbtion,K secretion and H secretion

The major use of it is in the treatment of hypertension most often in combination with a thiazide

it is often used in conjunction with a thiazide or loop diuretic to prevent potassium excretion that would otherwise occur with these drugs

Adverse effects

as it is chemically resembles some of the *** steroids, it does have minimal hormonal activity and may induce gynecomastia in males and menstural irregularities in females

E-Osmotic diuretics
e.g:mannitol

They are used to maintain renal flow following acute toxic ingestion of substances capable of producing acute renal failure

A mainstay of treatment for patients with

a- increased intracranial pressure
b-drug toxicity
c- trauma