(Mode of Action of Drugs)

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Chapter

1.4

Chapter

4.7 Diuretics and Antidiuretics

Diuretics and

Antidiuretics

Diuretics are the agents which increase the
rate of urine formation by the kidneys, or
which cause a net loss of sodium and
water in urine, i.e. the diuretics increase
the urine output of ions and fluids from
the kidneys.

Clinically, diuretics are among the most
widely prescribed drugs used in the
management of hypertension and various
edematous states like congestive heart
failure, nephrotic edema and in some cases
of edema in pregnancy.

Almost all diuretics exert their action
at the luminal surface of the renal tubule
cells. Their mechanism of action includes
interaction with specific membrane
transport proteins like thiazides,
furosemide etc., osmotic effects which
prevent the water permeable segments of
the nephron from absorbing water like
mannitol, and specific interaction with
enzyme like carbonic anhydrase
inhibitors i.e. acetazolamide, and
hormone receptors in renal epithelial cells
like spironolactone.

They are classified as in table 4.7.1.

BENZOTHIAZIDES

The main action of thiazides is exerted on

the early segment of distal tubule or cortical

diluting segment. They inhibit reabsorption

of sodium and chloride. The thiazides enter

the tubule partly by glomerular filtration

and partly by active secretion into the

proximal tubule. At usual therapeutic doses,

the major portion of the diuresis is due to

an inhibition of reabsorption in the more

distal parts of the nephron.

Pharmacodynamics

In maximal doses, chlorothiazide will

markedly increase excretion of water, Na+,

K+, Cl– and HCO 3 –. Chlorothiazide due to its

weak carbonic anhydrase activity, can cause

some loss of bicarbonate in therapeutic dose.

Because of the marked inhibitory action

on sodium reabsorption, a large amount of

sodium is made available to the distal tubule

where exchange of potassium with sodium

takes place, this causes potassium loss.

Thiazides, due to their direct action on

blood vessels and on sodium metabolism

produce a mild hypotension. They also tend