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Carbonic Anhydrase Inhibitor – Overview Of Its Uses And Mechanism Of Action

A carbonic anhydrase inhibitor is a kind of medication that works by inhibiting the action of carbonic anhydrase. Their use as anti-glaucoma drugs, diuretics, antiepileptics, and in the treatment of mountain sickness, gastric and duodenal ulcers, idiopathic intracranial hypertension, neurological diseases, and osteoporosis has been proven.

What Are Carbonic Anhydrase Inhibitors?

Carbonic anhydrase inhibitor decreases the activity of carbonic anhydrase, an enzyme that catalyzes the interaction of carbon dioxide and water to produce carbonic acid and eventually bicarbonate.

This lowers bicarbonate resorption from the proximal tubule in the kidneys, resulting in increased bicarbonate excretion and moderate increases in sodium and potassium excretion.

Carbonic anhydrase inhibitors have minor electrolyte effects and are not often utilized for their diuretic potential. Carbonic anhydrase inhibitors include acetazolamide, dichlorphenamide, and methazolamide.

Carbonic anhydrase inhibitor also reduces aqueous humor secretion (the clear fluid that fills the gap between the lens and the cornea of the eyeball), resulting in a reduction in intraocular pressure.

Carbonic anhydrase inhibitors are mainly used to treat glaucoma or other eye disorders where reducing intraocular blood pressure is considered advantageous. Acetazolamide is also used to treat and prevent acute mountain sickness (also known as altitude sickness) and treat certain kinds of epilepsy.

Certain hereditary muscular diseases may be treated with dichlorphenamide. Carbonic anhydrase inhibitors may also be used to treat other disorders.

Carbonic Anhydrase Inhibitors Uses

Glaucoma is treated with carbonic anhydrase inhibitors. Acetazolamide is also used as an anticonvulsant in the treatment of epilepsy to control certain seizures. It is also used to prevent or mitigate specific symptoms in mountain climbers who reach high altitudes and treat other problems as indicated by your doctor. These medications are only accessible with a doctor's prescription. This medicine is available in tablet and capsule formats for prolonged release.

Glaucoma Treatment

Acetazolamide is a carbonic anhydrase inhibitor that treats glaucoma. Glaucoma is a frequent eye ailment caused by damage to the optic nerve, which links the eye to the brain. It is generally caused by fluid accumulation in the front of the eye, which raises intraocular pressure. Glaucoma may cause visual loss if it is not detected and treated early.

Acetazolamide lowers intraocular pressure (IOP) through inactivating carbonic anhydrase and interfering with the sodium pump, which reduces aqueous humor production. The drug's effects on the renal tubules, where vital components of filtered blood are reabsorbed in the kidney, cause increased sodium, potassium, and water loss in the urine. A modest hyperchloremic metabolic acidosis may be seen in arterial blood gases.

Methazolamide also inhibits carbonic anhydrase. It has a longer elimination half-life than acetazolamide and is linked with fewer renal side effects.

Dorzolamide is a sulfonamide that acts as a carbonic anhydrase II inhibitor on the skin. It treats high intraocular pressure in people with open-angle glaucoma or ocular hypertension who are not responding to beta-blockers. Carbonic anhydrase II inhibition in the ciliary processes of the eye reduces aqueous humor secretion, likely by reducing the production of bicarbonate ions, resulting in a reduction in sodium and fluid transfer.

Brinzolamide (Azopt, Alcon Laboratories, Inc, and Befardin Fardi Medicals) is a carbonic anhydrase inhibitor used to treat open-angle glaucoma and ocular hypertension. It occurs in the form of many isoenzymes, the most active of which is carbonic anhydrase II. Azarga is the brand name for the combination of brinzolamide and timolol.


Some diuretics reduce the action of carbonic anhydrase in the proximal convoluted tubules, preventing bicarbonate reabsorption from the renal tubules. Reduced bicarbonate reabsorption causes the lower activity of the apical sodium hydrogen exchanger, resulting in diuresis owing to sodium retention in the renal tubules. Acetazolamide inhibits carbonic anhydrase. Dorzolamide, methazolamide, brinzolamide, and dichlorphenamide are some further examples.

Epilepsy Treatment

Acetazolamide is successful in treating most forms of seizures, including generalized tonic-clonic and focal seizures, as well as absence seizures. However, its value is limited since tolerance develops with long-term usage. The medicine is used intermittently to prevent seizures in cats with catamenial epilepsy.

Topiramate, a sulfur-containing antiseizure and antimigraine medication, is a poor inhibitor of carbonic anhydrase, namely subtypes II and IV. It is unknown if carbonic anhydrase inhibition adds to its therapeutic efficacy.

In rare circumstances, the carbonic anhydrase inhibition is powerful enough to produce clinically significant metabolic acidosis. Zonisamide is another sulfur-containing antiseizure medication that inhibits carbonic anhydrase mildly. Sultiame is another anticonvulsant medication in this family.

High Altitude Sickness Treatment

Because the partial pressure of oxygen is lower at high altitudes, humans must breathe more quickly to receive enough oxygen. When this occurs, the partial pressure of CO2 (pCO2) in the lungs falls, resulting in respiratory alkalosis.

Usually, the kidney excretes bicarbonate and causes compensatory metabolic acidosis, although this process takes many days. Carbonic anhydrase inhibitors, which restrict bicarbonate absorption in the kidney and assist rectify alkalosis, are a more rapid therapy. Carbonic anhydrase inhibitors have also been demonstrated to help with persistent mountain sickness.

Paper packaging of Acetazolamide
Paper packaging of Acetazolamide

Carbonic Anhydrase Inhibitor Mechanism Of Action

Carbonic anhydrase, which is found in the lumen of the kidney's proximal tubule, transforms carbonic acid into water and carbon dioxide. Diffusion allows water and carbon dioxide to enter the intracellular space.

The intracellular carbonic anhydrase enzyme converts water and carbon dioxide back into carbonic acid, dissociating into H+ and bicarbonate. Carbonic anhydrase inhibitor medicines work by inhibiting the enzyme, preventing bicarbonate resorption by tubular cells, resulting in bicarbonate retention in the tubular lumen.

The overall impact is urine alkalinization since there is more bicarbonate in the urine, and the blood becomes more acidic due to bicarbonate excretion. The diuretic action increases water excretion and lowers blood pressure.

Carbonic anhydrase inhibitors may cure altitude sickness by counteracting respiratory alkalosis caused by hyperventilation because of the resultant alterations in acid-base balance.

Carbonic anhydrase inhibitors diminish aqueous humor generation by the ciliary body epithelium in the eyes by lowering bicarbonate ion production and, presumably, fluid flow. Aqueous humor production decreases intraocular pressure, making these medications useful in glaucoma patients.

Carbonic Anhydrase Inhibitor Contraindications

Carbonic anhydrase inhibitors should not be utilized in individuals with hepatic diseases, such as cirrhosis or decreased hepatic function, due to the danger of fulminant hepatic necrosis.

However, liver damage is an uncommon adverse effect. The mechanism of hepatic damage is thought to be related to sulfonamide cross-reactivity. The harm happens days to weeks after the medicine is administered. The degree of hepatic damage varies from mixed or hepatocellular serum enzyme increases to acute fulminant liver failure.

Carbonic anhydrase inhibitors should be used with care in patients allergic to sulfonamides owing to the potential of deadly anaphylactic shock. Patients with a significant drug-induced rash in the past should avoid this class of drugs.

Specific HLA genotypes are substantially related to methazolamide-induced SJS/TEN, warranting genetic screening as a helpful predictor of SJS/TEN in Korean and Japanese patients before commencing methazolamide.

Because carbonic anhydrase inhibitors may create electrolyte imbalances, they are not indicated for individuals with hypokalemia, hyponatremia, metabolic acidosis, hyperchloremic acidosis, adrenal insufficiency, or severe renal impairment.

Nonsteroidal anti-inflammatory medicines (NSAIDs), beta-blockers, oral contraceptives, antifungals, lithium, metformin, clopidogrel, diuretics, and antiepileptics have all been linked to pharmacological interactions with carbonic anhydrase inhibitors. Carbonic anhydrase inhibitors produce urine alkalinization, which is thought to interfere with the excretion of many drugs.

Side Effects Of Carbonic Anhydrase Inhibitor

Changes in taste, weariness, stomach discomfort, diarrhea, nausea, vomiting, blurred vision, tinnitus, paresthesia, and headache are all possible side effects of carbonic anhydrase inhibitors.

Sulfonamide derivatives are included in both oral and topical medications. The sulfonamide structure may produce allergic responses such as rash and anaphylaxis, Stevens-Johnson syndrome (SJS), or toxic epidermal necrolysis in rare circumstances (TEN).

Burning, superficial punctate keratopathy and local inflammatory responses of the conjunctiva are all side effects of topical carbonic anhydrase inhibitors. Patients often complain about a harsh aftertaste.

Systemic carbonic anhydrase inhibitors are associated with more severe adverse effects, including metabolic acidosis, hypokalemia, aplastic anemia, agranulocytosis, nephrolithiasis, and fulminant liver necrosis. Urine alkalinization caused by increased bicarbonate excretion may accelerate the formation of calcium oxalate kidney stones.

Carbonic Anhydrase Inhibitor Precautions

Carbonic anhydrase inhibitors should be used cautiously due to significant side effects such as toxicity, hepatic failure, and SJS/TEN. All interprofessional healthcare team members, including clinicians, nurses, and pharmacists, must be aware of these drugs' contraindications and adverse effects.

Effective team and patient communication are critical for minimizing side effects. Carbonic anhydrase inhibitors have no antidote; consequently, pharmaceutical usage in individuals with reduced renal and hepatic function needs continuous monitoring.

Nurses may provide patient counseling and function as a point of contact for professionals. Pharmacists should review medication reconciliation for drug-drug interactions and guide patients on a dose, administration, and possible adverse effects. This interdisciplinary approach to treatment will enhance results and prevent possible side effects when administering carbonic anhydrase inhibitors.

The interprofessional healthcare team is responsible for ensuring that the patient knows the difference between administration by oral and topical methods. In the case of severe glaucoma, patients may be taking several topical and oral intraocular pressure-lowering medications and must be cautious to adhere to the appropriate amounts.

Ophthalmic eye drop bottles with distinct cap colors may aid in avoiding misunderstanding and overdosage. Many randomized controlled studies and meta-analyses have shown the safety and effectiveness of topical carbonic anhydrase inhibitors, such as dorzolamide and brinzolamide, when used in conjunction with other glaucoma drugs, such as prostaglandin analogs or beta-blockers.

People Also Ask

Why Carbonic Anhydrase Inhibitors Are Weak Diuretics?

Acetazolamide (Diamox) and other carbonic anhydrase inhibitors are diuretics. They reduce the proximal renal tubule's production of hydrogen ions, resulting in increased bicarbonate and sodium loss.

What Is The Function Of Carbonic Anhydrase Enzyme?

The carbonic anhydrase enzyme catalyzes a crucial process in life: the bidirectional conversion of carbon dioxide (CO2) and water (H2O) into bicarbonate (HCO3-) and protons (H+). These enzymes influence various physiological processes inside and across the body's different compartments.

What Are Carbonic Anhydrase Inhibitors Used For?

Glaucoma is treated with carbonic anhydrase inhibitors. Acetazolamide is also used as an anticonvulsant in the treatment of epilepsy to control certain seizures.

Which Drug Is A Carbonic Anhydrase Inhibitor?

Carbonic anhydrase inhibitors may be given topically, orally, or intravenously. Currently available carbonic inhibitor drugs include acetazolamide, methazolamide, dorzolamide, brinzolamide, diclofenamide, ethoxzolamide, and zonisamide.


Carbonic anhydrase inhibitors (CAIs) decrease sodium reabsorption by blocking carbonic anhydrase enzymes in the proximal convoluted tubule, causing diuresis and metabolic acidosis. Carbonic anhydrase inhibitors also reduce carbonic anhydrase activity in the eyes and glial cells, resulting in lower aqueous humor and cerebrospinal fluid (CSF) production.

Acetazolamide is the most common carbonic anhydrase inhibitor. Carbonic anhydrase inhibitors are mainly used to treat altitude sickness and edema in people with metabolic alkalosis and glaucoma and as adjuvant therapy for some forms of epilepsies and elevated intracranial pressure. Carbonic anhydrase inhibitors are not used to treat high blood pressure.

About The Authors

Suleman Shah

Suleman Shah - Suleman Shah is a researcher and freelance writer. As a researcher, he has worked with MNS University of Agriculture, Multan (Pakistan) and Texas A & M University (USA). He regularly writes science articles and blogs for science news website immersse.com and open access publishers OA Publishing London and Scientific Times. He loves to keep himself updated on scientific developments and convert these developments into everyday language to update the readers about the developments in the scientific era. His primary research focus is Plant sciences, and he contributed to this field by publishing his research in scientific journals and presenting his work at many Conferences. Shah graduated from the University of Agriculture Faisalabad (Pakistan) and started his professional carrier with Jaffer Agro Services and later with the Agriculture Department of the Government of Pakistan. His research interest compelled and attracted him to proceed with his carrier in Plant sciences research. So, he started his Ph.D. in Soil Science at MNS University of Agriculture Multan (Pakistan). Later, he started working as a visiting scholar with Texas A&M University (USA). Shah’s experience with big Open Excess publishers like Springers, Frontiers, MDPI, etc., testified to his belief in Open Access as a barrier-removing mechanism between researchers and the readers of their research. Shah believes that Open Access is revolutionizing the publication process and benefitting research in all fields.

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