Carbonic anhydrase inhibitors are a class of pharmaceuticals that suppress
the activity of carbonic anhydrase. Their clinical use has been established
as antiglaucoma agents, diuretics, antiepileptics, in the management of
mountain sickness, gastric and duodenal ulcers, neurological disorders, or
osteoporosis. Medical Uses
Carbonic anhydrase inhibitors are primarily used for the treatment of
glaucoma. They may also be used to treat seizure disorder and acute mountain
sickness. Because they encourage solubilization and excretion of uric
acid, they can be used in the treatment of gout.
= Glaucoma = Acetazolamide is an inhibitor of
carbonic anhydrase. It is used for glaucoma, epilepsy, idiopathic
intracranial hypertension, and altitude sickness.
Methazolamide is also a carbonic anhydrase inhibitor. It has a longer
elimination half-life than acetazolamide and is less associated with adverse
effects to the kidney. Dorzolamide is a sulfonamide and topical
carbonic anhydrase II inhibitor. It is indicated for the reduction of elevated
intraocular pressure in patients with open-angle glaucoma or ocular
hypertension and who are insufficiently responsive to beta-blockers. Inhibition
of carbonic anhydrase II in the ciliary processes of the eye decreases aqueous
humor secretion, presumably by slowing the formation of bicarbonate ions with
subsequent reduction in sodium and fluid transport.
Brinzolamide is a carbonic anhydrase inhibitor used to lower intraocular
pressure in patients with open-angle glaucoma or ocular hypertension. It
exists as a number of isoenzymes, the most active of which is carbonic
anhydrase II. The combination of brinzolamide with timolol is marketed
under the trade name Azarga. = Diuretic =
Acetazolamide can act as a mild diuretic by reducing NaCl and bicarbonate
reabsorption in the proximal tubule. However, the distal segment partially
compensates for the sodium loss, and the bicarbonaturia will produce a metabolic
acidosis, further reducing the effect. = Epilepsy =
Topiramate is a weak inhibitor of carbonic anhydrase, particularly
subtypes II and IV. It is a sulfamate-substituted monosaccharide,
related to fructose. In the US, it is approved by the U.S. Food and Drug
Administration as an anticonvulsant to treat epilepsy and Lennox-Gastaut
syndrome, and also to prevent migraine headaches. In rare cases, the inhibition
of carbonic anhydrase may be strong enough to cause metabolic acidosis of
clinical importance. = Altitude Sickness =
At high altitude, the partial pressure of oxygen is lower and people have to
breathe more rapidly to get adequate oxygen. When this happens, the partial
pressure of CO2 in the lungs decreases, causing a respiratory alkalosis. This
would normally be compensated by the kidney excreting bicarbonate and causing
compensatory metabolic acidosis, but this mechanism takes several days. A
more immediate treatment is carbonic anhydrase inhibitors, which prevent
bicarbonate uptake in the kidney and help correct the alkalosis. Carbonic
anhydrase inhibitors have also been shown to improve chronic mountain
sickness by reducing erythropoietin and the resulting polycytemia.
Contraindications Hepatic cirrhosis
Adverse effects Loss of bicarbonate may result in
metabolic acidosis. Alkaline urine may increase the likelihood of kidney
stones. Natural sources
Ellagitannins extracted from the pericarps of Punica granatum, the
pomegranate, such as punicalin, punicalagin, granatin B,
gallagyldilactone, casuarinin, pedunculagin and tellimagrandin I, are
carbonic anhydrase inhibitors. References
External links Carbonic anhydrase inhibitors at the US
National Library of Medicine Medical Subject Headings
MedlinePlus DrugInfo uspdi-202114