Carbonic anhydrase inhibitor
|Carbonic anhydrase inhibitor|
|Biological target||Carbonic anhydrase|
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.
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.
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 (trade names Azopt, Alcon Laboratories, Inc, Befardin Fardi Medicals) 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 (CA-II). The combination of brinzolamide with timolol is marketed under the trade name Azarga.
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.
Acetazolamide is effective in the treatment of most types of seizures, including generalized tonic-clonic and focal seizures and especially absence seizures, although it has limited utility because tolerance develops with chronic use. The drug is occasionally used on an intermittent basis to prevent seizures in catamenial epilepsy.
The sulfur-containing antiseizure and antimigraine drug topiramate is a weak inhibitor of carbonic anhydrase, particularly subtypes II and IV. Whether carbonic anhydrase inhibition contributes to its clinical activity is not known. In rare cases, the inhibition of carbonic anhydrase may be strong enough to cause metabolic acidosis of clinical importance. Zonisamide is another sulfur containing antizure drug that weakly inhibits carbonic anhydrase.
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 (pCO2) decreases (is "blown off"), 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.
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.
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- Carbonic anhydrase inhibitors at the US National Library of Medicine Medical Subject Headings (MeSH)
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