Carbonic anhydrase inhibitor

Last updated
Carbonic anhydrase inhibitor
Drug class
Acetazolamide.svg
Class identifiers
Use Glaucoma
ATC code S01EC
Biological target Carbonic anhydrase
Clinical data
Drugs.com Drug Classes
External links
MeSH D002257
In Wikidata

Carbonic anhydrase inhibitors are a class of pharmaceuticals that suppress the activity of carbonic anhydrase. Their clinical use has been established as anti-glaucoma agents, diuretics, antiepileptics, in the management of mountain sickness, gastric and duodenal ulcers, idiopathic intracranial hypertension, neurological disorders, or osteoporosis. [1] [2] [3]

Contents

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. [4]

Glaucoma

Acetazolamide is an inhibitor of carbonic anhydrase. It is used for glaucoma, epilepsy (rarely), idiopathic intracranial hypertension, and altitude sickness.

For the reduction of intraocular pressure (IOP), acetazolamide inactivates carbonic anhydrase and interferes with the sodium pump, which decreases aqueous humor formation and thus lowers IOP. Systemic effects include increased loss of sodium, potassium, and water in the urine, secondary to the drug's effects on the renal tubules, where valuable components of filtered blood are re-absorbed in the kidney. Arterial blood gases may show a mild hyperchloremic metabolic acidosis. [5]

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. [6] [7] [8]

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.[ citation needed ]

Brinzolamide (trade name Azopt) 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.[ citation needed ]

Diuretic

Some diuretics [9] inhibit the activity of carbonic anhydrase in proximal convoluted tubules and prevent reabsorption of bicarbonates from renal tubules. Lowered reabsorption of bicarbonates results in decreased activity of the apical sodium hydrogen exchanger, causing diuresis due to retention of sodium in the renal tubules. Acetazolamide is a carbonic anhydrase inhibitor. Other examples are:

CSF regulation

Carbonic anhydrase inhibitors may be used to reduce the production of cerebrospinal fluid (CSF) in the brain. For instance, a cerebrospinal fluid leak may initially be treated medically with this medication to reduce the volume of leakage, and promote healing of the fistula. Similarly, in Idiopathic intracranial hypertension, reduction of CSF production by the choroid plexi may reduce intracranial pressures and reduce symptoms of elevated intracranial pressure such as retroorbital headaches and loss of vision. The mechanism is thought to involve inhibition of carbonic anhydrase (CA) within the choroidal epithelial cells, reducing the production of protons which are necessary for the osmotic transport of water and ions which constitute CSF.

Epilepsy

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. [10]

The sulfur-containing antiseizure and antimigraine drug topiramate is a weak inhibitor of carbonic anhydrase, particularly subtypes II and IV. [11] 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 antiseizure drug that weakly inhibits carbonic anhydrase.

Sultiame is also an example of an anticonvulsant drug of this class.

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 (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. [12] Carbonic anhydrase inhibitors have also been shown to improve chronic mountain sickness. [13]

Contraindications

Adverse effects

Loss of bicarbonate may result in metabolic acidosis. [15]

In plants

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. [16]

Related Research Articles

<span class="mw-page-title-main">Acetazolamide</span> Chemical compound

Acetazolamide, sold under the trade name Diamox among others, is a medication used to treat glaucoma, epilepsy, altitude sickness, periodic paralysis, idiopathic intracranial hypertension, heart failure and to alkalinize urine. It may be used long term for the treatment of open angle glaucoma and short term for acute angle closure glaucoma until surgery can be carried out. It is taken by mouth or injection into a vein. Acetazolamide is a first generation carbonic anhydrase inhibitor and it decreases the ocular fluid and osmolality in the eye to decrease intraocular pressure.

<span class="mw-page-title-main">Loop diuretic</span> Diuretics that act at the ascending limb of the loop of Henle in the kidney

Loop diuretics are diuretics that act on the Na-K-Cl cotransporter along the thick ascending limb of the loop of Henle in nephrons of the kidneys. They are primarily used in medicine to treat hypertension and edema often due to congestive heart failure or chronic kidney disease. While thiazide diuretics are more effective in patients with normal kidney function, loop diuretics are more effective in patients with impaired kidney function.

<span class="mw-page-title-main">Amiloride</span> Medication

Amiloride, sold under the trade name Midamor among others, is a medication typically used with other medications to treat high blood pressure or swelling due to heart failure or cirrhosis of the liver. Amiloride is classified as a potassium-sparing diuretic. Amiloride is often used together with another diuretic, such as a thiazide or loop diuretic. It is taken by mouth. Onset of action is about two hours and it lasts for about a day.

<span class="mw-page-title-main">Chlortalidone</span> Thiazide-like diuretic drug

Chlortalidone, also known as chlorthalidone, is a thiazide-like diuretic drug used to treat high blood pressure, swelling, diabetes insipidus, and renal tubular acidosis. Because chlortalidone is reliably effective in most patients with high blood pressure, it is considered a preferred initial treatment. It is also used to prevent calcium-based kidney stones. It is taken by mouth. Effects generally begin within three hours and last for up to three days. Long-term treatment with chlortalidone is more effective than hydrochlorothiazide for prevention of heart attack or stroke.

<span class="mw-page-title-main">Thiazide</span> Class of chemical compounds

Thiazide refers to both a class of sulfur-containing organic molecules and a class of diuretics based on the chemical structure of benzothiadiazine. The thiazide drug class was discovered and developed at Merck and Co. in the 1950s. The first approved drug of this class, chlorothiazide, was marketed under the trade name Diuril beginning in 1958. In most countries, thiazides are the least expensive antihypertensive drugs available.

<span class="mw-page-title-main">Metabolic alkalosis</span> Medical condition

Metabolic alkalosis is a metabolic condition in which the pH of tissue is elevated beyond the normal range (7.35–7.45). This is the result of decreased hydrogen ion concentration, leading to increased bicarbonate, or alternatively a direct result of increased bicarbonate concentrations. The condition typically cannot last long if the kidneys are functioning properly.

Hyperchloremic acidosis is a form of metabolic acidosis associated with a normal anion gap, a decrease in plasma bicarbonate concentration, and an increase in plasma chloride concentration. Although plasma anion gap is normal, this condition is often associated with an increased urine anion gap, due to the kidney's inability to secrete ammonia.

<span class="mw-page-title-main">Renal tubular acidosis</span> Medical condition

Renal tubular acidosis (RTA) is a medical condition that involves an accumulation of acid in the body due to a failure of the kidneys to appropriately acidify the urine. In renal physiology, when blood is filtered by the kidney, the filtrate passes through the tubules of the nephron, allowing for exchange of salts, acid equivalents, and other solutes before it drains into the bladder as urine. The metabolic acidosis that results from RTA may be caused either by insufficient secretion of hydrogen ions into the latter portions of the nephron or by failure to reabsorb sufficient bicarbonate ions from the filtrate in the early portion of the nephron. Although a metabolic acidosis also occurs in those with chronic kidney disease, the term RTA is reserved for individuals with poor urinary acidification in otherwise well-functioning kidneys. Several different types of RTA exist, which all have different syndromes and different causes. RTA is usually an incidental finding based on routine blood draws that show abnormal results. Clinically, patients may present with vague symptoms such as dehydration, mental status changes, or delayed growth in adolescents.

<span class="mw-page-title-main">Ethoxzolamide</span> Chemical compound

Ethoxzolamide is a sulfonamide medication that functions as a carbonic anhydrase inhibitor. It is used in the treatment of glaucoma and duodenal ulcers, and as a diuretic. It may also be used in the treatment of some forms of epilepsy.

<span class="mw-page-title-main">Pseudohypoaldosteronism</span> Medical condition

Pseudohypoaldosteronism (PHA) is a condition that mimics hypoaldosteronism. However, the condition is due to a failure of response to aldosterone, and levels of aldosterone are actually elevated, due to a lack of feedback inhibition.

<span class="mw-page-title-main">Methazolamide</span> Chemical compound

Methazolamide is a potent carbonic anhydrase inhibitor. It is indicated in the treatment of increased intraocular pressure (IOP) in chronic open-angle glaucoma and secondary glaucoma. Also it is used preoperatively in acute angle-closure (narrow-angle) glaucoma where lowering the IOP is desired before surgery.

<span class="mw-page-title-main">Brinzolamide</span> Chemical compound

Brinzolamide is a carbonic anhydrase inhibitor used to lower intraocular pressure in patients with open-angle glaucoma or ocular hypertension.

<span class="mw-page-title-main">Dorzolamide</span> Chemical compound

Dorzolamide, sold under the brand name Trusopt among others, is a medication used to treat high pressure inside the eye, including in cases of glaucoma. It is used as an eye drop. Effects begin within three hours and last for at least eight hours. It is also available as the combination dorzolamide/timolol.

Contraction alkalosis refers to the increase in blood pH that occurs as a result of fluid losses. The change in pH is especially pronounced with acidic fluid losses caused by problems like vomiting.

Normal anion gap acidosis is an acidosis that is not accompanied by an abnormally increased anion gap.

<span class="mw-page-title-main">Carbonic anhydrase 9</span> Protein-coding gene in the species Homo sapiens

Carbonic anhydrase IX is an enzyme that in humans is encoded by the CA9 gene. It is one of the 14 carbonic anhydrase isoforms found in humans and is a transmembrane dimeric metalloenzyme with an extracellular active site that facilitates acid secretion in the gastrointestinal tract. CA IX is overexpressed in many types of cancer including clear cell renal cell carcinoma (RCC) as well as carcinomas of the cervix, breast and lung where it promotes tumor growth by enhancing tumor acidosis.

<span class="mw-page-title-main">Electrogenic sodium bicarbonate cotransporter 1</span> Protein-coding gene in the species Homo sapiens

Electrogenic sodium bicarbonate cotransporter 1, sodium bicarbonate cotransporter is a membrane transport protein that in humans is encoded by the SLC4A4 gene.

<span class="mw-page-title-main">Diuretic</span> Substance that promotes the production of urine

A diuretic is any substance that promotes diuresis, the increased production of urine. This includes forced diuresis. A diuretic tablet is sometimes colloquially called a water tablet. There are several categories of diuretics. All diuretics increase the excretion of water from the body, through the kidneys. There exist several classes of diuretic, and each works in a distinct way. Alternatively, an antidiuretic, such as vasopressin, is an agent or drug which reduces the excretion of water in urine.

<span class="mw-page-title-main">Carbonic anhydrase</span> Class of enzymes

The carbonic anhydrases form a family of enzymes that catalyze the interconversion between carbon dioxide and water and the dissociated ions of carbonic acid. The active site of most carbonic anhydrases contains a zinc ion. They are therefore classified as metalloenzymes. The enzyme maintains acid-base balance and helps transport carbon dioxide.

Brinzolamide/brimonidine, sold under the brand name Simbrinza, is a fixed-dose combination medication used to reduce intra-ocular pressure in adults with ocular hypertension or in those with an eye condition known as open-angle glaucoma. It contains brinzolamide and brimonidine tartrate. It is used as an eye drop.

References

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  4. Hyperuricemia Medication~medication at eMedicine
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  15. Leaf, Alexander; Schwartz, William B.; Relman, Arnold S. (1954). "Oral Administration of a Potent Carbonic Anhydrase Inhibitor (Diamox)". New England Journal of Medicine. 250 (18): 759–64. doi:10.1056/NEJM195405062501803. PMID   13165895.
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