Pharmacology for Dentistry

208 Section 4/ Drugs Acting on Cardiovascular & Urinary System

with transport in the late segments of the
nephron by blocking the luminal Na+ channels
thus indirectly inhibiting K+ excretion. They
slightly increase sodium excretion and decrease
potassium excretion, particularly when it is high
due to high potassium intake or use of diuretics
that enhances potassium loss.

In addition to these effects, all the
potassium sparing diuretics are capable of
inhibiting urinary H+ secretion in the distal
tubule and cortical collecting duct.

Pharmacokinetics

About 50% of an oral dose of each agent
is absorbed. Triamterene is about 60 percent
bound to plasma proteins, while amiloride
is bound to a lesser extent. Both drugs are
secreted in the proximal tubule, presumably
by the organic cation secretory mechanism.

Adverse Reactions

The serious toxic effect is hyperkalemia.
Triamterene produces relatively few other
side effects which includes nausea,
vomiting, dizziness etc. Megaloblastic
anaemia has been reported in patients with
alcoholic cirrhosis, which is probably due
to inhibition of dihydrofolate reductase in
patients with reduced folic acid intake.

Therapeutic Uses

Both drugs are used in conjunction with
other diuretics like thiazide or loop diuretics
to augment natriuresis and reduce loss of
potassium. Triamterene may be used in the
treatment of congestive heart failure, cirrhosis
and the edema caused by secondary
hyperaldosteronism. Amiloride is also useful
in lithium induced diabetes insipidus.

POTASSIUM SPARING DIURETICS

SPIRONOLACTONE

It is a steroid and aldosterone antagonist.

Aldosterone acts on the late distal tubules

and collecting tubule cells by combining

with an intracellular receptor which induces

the formation of aldosterone induced

protein, which promotes Na+ reabsorption

and K+ secretion.

Spironolactone also increases Ca2+

excretion through a direct effect on tubular

transport. In relatively high concentrations,

it can inhibit the biosynthesis of aldosterone.

Pharmacokinetics

The oral bioavailability of spironolac-

tone is about 70%. It is extensively bound to

plasma proteins and is completely metabo-

lized in liver. Canrenone is a major active

metabolite of spironolactone, which can be

converted enzymatically into canrenoate

(hydrolytic product). Canrenoate has no

intrinsic activity, but it can exert their effects

by virtue of its interconversion with

canrenone.

Adverse Reactions

In patients with renal insufficiency,

spironolactone may induce hyperkalemia.

Minor side effects include drowsiness con-

fusion, gastrointestinal upset, gynaecomastia

and menstrual irregularities.

Therapeutic Uses

Spironolactone is generally used in

combination with other, more efficacious

diuretics.