Carbonic anhydrase inhibitor
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 name Azopt, Alcon Laboratories, Inc.) 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.
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 (FDA) 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.
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 by reducing erythropoietin and the resulting polycytemia.
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)
- MedlinePlus DrugInfo uspdi-202114
Competitive inhibitionUncompetitive inhibitionNon-competitive inhibitionSuicide inhibitionMixed inhibition Class Substrate Oxidoreductase (EC 1) Transferase (EC 2) Hydrolase (EC 3) Lyase (EC 4)
- 4.2 Carbonic anhydrase
(and etacrynic acid)
CA inhibitors (at PT) Loop (Na-K-Cl at AL) Thiazides (Na-Cl at DCT,
Thiazide-likes (primarily DCT) Potassium-sparing (at CD) ESC blockers Aldosterone antagonists Osmotic diuretics (PT, DL) Vasopressin receptor inhibitors
(DCT and CD)
OtherIndex of the circulatory system Description Disease Treatment Sympathomimetics Parasympathomimetics muscarinic muscarinic/nicotinic Acetylcholinesterase inhibitors Carbonic anhydrase inhibitors/
Beta blocking agents Prostaglandin analogues (F2α) Other agentsIndex of the eye Description Disease Treatment