CLINICAL PHARMACOLOGY
Acetazolamide is a potent carbonic anhydrase inhibitor,
effective in the control of fluid secretion (e. g., some
types of glaucoma), in the treatment of certain convulsive
disorders (e. g., epilepsy) and in the promotion of diuresis
in instances of abnormal fluid retention (e. g., cardiac
edema).
Acetazolamide is not a mercurial diuretic. Rather, it is
a nonbacteriostatic sulfonamide possessing a chemical structure
and pharmacological activity distinctly different from the
bacteriostatic sulfonamides.
Acetazolamide is an enzyme inhibitor that acts specifically
on carbonic anhydrase, the enzyme that catalyzes the reversible
reaction involving the hydration of carbon dioxide and the
dehydration of carbonic acid. In the eye, this inhibitory
action of acetazolamide decreases the secretion of aqueous
humor and results in a drop in intraocular pressure, a reaction
considered desirable in cases of glaucoma and even in certain
nonglaucomatous conditions. Evidence seems to indicate that
acetazolamide has utility as an adjuvant in the treatment
of certain dysfunctions of the central nervous system (e.
g., epilepsy). Inhibition of carbonic anhydrase in this
area appears to retard abnormal, paroxysmal, excessive discharge
from central nervous system neurons. The diuretic effect
of acetazolamide is due to its action in the kidney on the
reversible reaction involving hydration of carbon dioxide
and dehydration of carbonic acid. The result is renal loss
of HCO 3 ion, which carries out sodium, water, and potassium.
Alkalinization of the urine and promotion of diuresis are
thus effected. Alteration in ammonia metabolism occurs due
to increased reabsorption of ammonia by the renal tubules
as a result of urinary alkalinization.
Placebo- controlled clinical trials have shown that prophylactic
administration of acetazolamide at a dose of 250 mg every
eight to 12 hours (or a 500 mg controlled-release capsule
once daily) before and during rapid ascent to altitude results
in fewer and or less severe symptoms (such as headache,
nausea, shortness of breath, dizziness, drowsiness, and
fatigue) of acute mountain sickness (AMS). Pulmonary function
(e. g., minute ventilation, expired vital capacity, and
peak flow) is greater in the acetazolamide treated group,
both in subjects with AMS and asymptomatic subjects. The
acetazolamide treated climbers also had less difficulty
in sleeping.
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