Pharmacology for Dentistry

Diuretics and Antidiuretics 207

It does not inhibit carbonic anhydrase.
Loss of potassium is less marked but chance
of hypochloremic alkalosis are greater. It is
an irritant and upon oral administration it
produces diarrhoea, gastrointestinal
bleeding may occur at higher dose. Chances
of hearing loss are greater. So, due to their
uniform toxicity, they are no longer used.

CARBONIC ANHYDRASE INHIBITORS

ACETAZOLAMIDE

It is a potent, noncompetitive reversible
carbonic anhydrase inhibitor. Carbonic
anhydrase is an enzyme which catalyses the
reversible reaction

H 2 O + CO 2 H 2 CO 3
Carbonic anhydrase influences the
tubular reabsorption of sodium in proximal
tubule where biocarbonate absorption occurs
and in the distal tubule where sodium is
exchanged for potassium or hydrogen ion
and bicarbonate is formed as the
accompanying anion. The hydration of
carbon dioxide takes place under the
influence of enzyme carbonic anhydrase
which forms carbonic acid which dissociates
and breaks into hydrogen and carbonate ions.

Acetazolamide inhibits the enzyme
carbonic anhydrase, and interferes with the
ability of the renal tubules to produce and
secrete hydrogen ions. And, the diuretic
action is due to the decreased sodium
biocarbonate absorption in proximal tubules
and diminished hydrogensodium exchange
in the distal tubules.

Pharmacokinetics

All the carbonic anhydrase inhibitors
are well absorbed after oral administra-

tion. Peak concentrations in plasma occur

with in 2 hours and persists for 12 hours

after a single dose. Acetazolamide is ex-

creted unchanged in urine. Ethoxzolamide

is similar to acetazolamide but more

potent.

Adverse Reactions

Serious toxic reactions include acidosis,

hypokalemia, drowsiness and paresthesia

are common with larger doses.

Hypersensitivity reactions are rare, they

consists of fever, skin reactions, bone-

marrow depression and sulfonamide like

renal lesions.

Drug induced osteomalacia has been

reported with the simultaneous use of

phenytoin.

Therapeutic Uses

Carbonic anhydrase inhibitors are rarely

used as primary diuretics, because of self-

limiting action, production of acidosis, and

hypokalemia. They are used in:

i. Glaucoma, as adjuvant to miotics.

ii. In urinary tract infections or to

alkalinise urine to promote the excre-

tion of acidic drugs.

iii. In petit mal epilepsy as adjuvant.

iv. In the management of periodic paraly-

sis.

v. Effective in ameliorating the symptoms

of acute mountain sickness.

DIRECTLY ACTING DIURETICS

TRIAMTERENE AND AMILORIDE

Triamterene and amiloride are non-steroidal

potassium sparing diuretics, which interfere