Carbonic anhydrase inhibitors: Uses, common brands, and safety info

Carbonic anhydrase inhibitors are medications that are primarily used to treat glaucoma. As antiglaucoma agents, they can help decrease intraocular pressure caused by excess fluid in the eye. Certain carbonic anhydrase inhibitors may also be used for other purposes, including the treatment of altitude sickness, heart failure, and epilepsy. They block the carbonic anhydrase enzyme, which is a protein substance that converts carbonic acid, or carbonate, into water and carbon dioxide.  Blocking the carbonic anhydrase enzyme leads to increased levels of bicarbonate in the urine and increased excretion of water from the body.  

Continue reading to learn more about the different types of carbonic anhydrase inhibitors, their uses, and side effects.

Other carbonic anhydrase inhibitors

• Diamox Sequels (acetazolamide XR)

• Keveyis (dichlorphenamide)

• Daranide (dichlorphenamide)

• Glauctabs (methazolamide)

• MZM (methazolamide) 

• Azarga (brinzolamide and timolol)

• MSD (dorzolamide and timolol)

What are carbonic anhydrase inhibitors?

Carbonic anhydrase inhibitors, or CAIs, decrease the production of aqueous humor in the eyes. They are used to help reduce intraocular pressure and other symptoms of glaucoma. These drugs are also weak diuretics that work in the proximal tubule of the kidney. With mild diuretic effects, carbonic anhydrase inhibitors can help relieve edema, or swelling, caused by congestive heart failure. These medications can also be prescribed to treat altitude sickness and seizure disorders, among other conditions. 

Carbonic anhydrase inhibitors can be administered as oral tablets, intravenous injections, or topical solutions and suspensions. Acetazolamide, methazolamide, and dichlorphenamide are examples of systemic carbonic inhibitors that are administered as oral tablets or injections. Brinzolamide and dorzolamide are applied topically as eye drops. These eye drops may also contain other medications like prostaglandin analogs. The dosage of carbonic anhydrase inhibitors will depend on the condition being treated. For example, 250 mg to 1000 mg of acetazolamide is usually prescribed for the treatment of glaucoma while higher doses are prescribed for altitude sickness.

How do carbonic anhydrase inhibitors work?

Carbonic anhydrase is an enzyme that helps convert carbonic acid into water and carbon dioxide. It can also help convert water and carbon dioxide back into carbonic acid, which then separates into bicarbonate and hydrogen ions. Carbonic anhydrase plays a role in regulating the acid-base balance in the body. It exists in different areas of the body, including the red blood cells, eyes, proximal tubules of the kidney, and lungs. Carbonic anhydrase inhibitors can work in different parts of the body. They can block carbonic anhydrase II, a form of the enzyme found in the kidney tubules. These medications work by preventing the reabsorption of bicarbonate in the proximal tubules of the kidneys, which leads to increased levels of bicarbonate in the kidney tubules. This mechanism of action results in increased acidity of the blood and alkalization in the urine. Increased bicarbonate in the kidney tubules also pulls water into the urine, leading to a mild diuretic effect. Carbonic anhydrase is also found in the ciliary epithelium of the eye. This enzyme is involved with the secretion of aqueous humor, or fluid, in the eye. Inhibition of carbonic anhydrase can decrease aqueous humor levels and intraocular pressure. These medications can help reduce high pressure in the eye caused by glaucoma and other eye conditions. 

What are carbonic anhydrase inhibitors used for?

Carbonic anhydrase inhibitors are used in the treatment of various health conditions. They are primarily used as antiglaucoma agents, although they also have other FDA approved and off-label uses. For example, people who experience altitude sickness may have symptoms like hyperventilation and respiratory alkalosis. Acetazolamide can help improve oxygenation and pulmonary gas exchange in the lungs. The uses of carbonic anhydrase inhibitors include the treatment of:

• Glaucoma (angle-closure and open-angle glaucoma)

• Edema (due to congestive heart failure)

• Altitude sickness or acute mountain sickness

• Epilepsy 

• Sleep apnea

• Idiopathic intracranial hypertension (cerebrospinal fluid leak)

• Metabolic alkalosis (due to COPD)

• Contrast-induced nephropathy prevention

Who can take carbonic anhydrase inhibitors?

Adults

Adults may be prescribed a carbonic anhydrase inhibitor for various purposes. Adults with glaucoma or other eye conditions might be prescribed a topical carbonic anhydrase inhibitor. Topical eye drops include dorzolamide (as a 2% ophthalmic solution) and brinzolamide (as a 1% ophthalmic suspension). Adults can also be given carbonic anhydrase inhibitors as oral tablets and IV injections. Systemic forms of carbonic anhydrase inhibitors are prescribed when topical forms are ineffective. 

Children

Carbonic anhydrase inhibitors may be used for treating certain seizures in children. In some cases, these medications may be used for other conditions like glaucoma or altitude sickness in children. However, there may not be specific information available on the use of carbonic anhydrase inhibitors for certain conditions in children. Dosage may be determined by a healthcare provider and based on the child’s body weight. 

Seniors 

There is no specific dosing information or difference in the side effects of carbonic anhydrase inhibitors in seniors versus adults. There may be an increased risk of certain side effects, such as metabolic acidosis, in older adults with reduced kidney function. A healthcare provider will evaluate the use of carbonic anhydrase inhibitors in older adults on a case-by-case basis. Some geriatric patients may need to receive a lower dose of these medications or be monitored more closely.

Can you take carbonic anhydrase inhibitors while pregnant or breastfeeding?

There is not enough research on the use of carbonic anhydrase inhibitors in women during pregnancy. However, studies have shown that these medications can cause fetal harm in animals. Therefore, carbonic anhydrase inhibitors should only be used during pregnancy if the benefits outweigh the risks. Carbonic anhydrase inhibitors are not recommended during breastfeeding. This drug may pass into the breastmilk and cause harm to nursing babies. If you are pregnant or planning to become pregnant, or if you are breastfeeding or planning to breastfeed, tell your healthcare provider before taking a carbonic anhydrase inhibitor. 

Are carbonic anhydrase inhibitors safe?

Carbonic anhydrase inhibitors are generally safe if used as prescribed by a healthcare provider. Despite specific side effects caused by a rapid decrease in bicarbonate ions in the body, this class of medications has a good safety record. Adverse effects may be more common with carbonic anhydrase inhibitors that are given as an oral tablet or IV injection rather than an eye drop.Tell your healthcare provider if you have a history of any of the following before taking a carbonic anhydrase inhibitor:

• Chronic lung diseases

• Kidney disease

• Liver disease

• Low potassium or sodium levels in the blood

• Electrolyte imbalances

• Diabetes

• Gout

• Allergic reactions to carbonic anhydrase inhibitors

• Allergic reactions to sulfa drugs 

Black Box Warnings

There are no black box warnings for carbonic anhydrase inhibitors. 

Recalls

There are no current carbonic anhydrase inhibitor drug recalls.

Carbonic anhydrase inhibitor restrictions

Caution should be used when taking certain medications with carbonic anhydrase inhibitors. Carbonic anhydrase inhibitors are not generally recommended to be taken with aspirin. Combining carbonic anhydrase inhibitors with aspirin may cause severe side effects, such as metabolic acidosis, rapid breathing, coma, or death. Other medications like phenytoin, primidone, methenamine, and lithium may also interact with carbonic anhydrase inhibitors. The use of carbonic anhydrase inhibitors may cause changes in blood sugar levels and electrolyte changes. People with diabetes and kidney problems need to use caution while taking carbonic anhydrase inhibitors. Glucose, potassium, and sodium bicarbonate levels may need to be monitored throughout treatment. Carbonic anhydrase inhibitors may cause you to feel drowsy, dizzy, and tired. Do not operate any heavy machinery or drive before understanding how these medications affect you. Tell your healthcare provider if you have other medical conditions or if you are taking other medications, including prescription drugs, over-the-counter medicines, and herbal supplements. 

Are carbonic anhydrase inhibitor controlled substances?

No, carbonic anhydrase inhibitors are not controlled substances.

Common carbonic anhydrase inhibitors side effects

Side effects of carbonic anhydrase inhibitors depend on the drug formulation. Common side effects of carbonic anhydrase inhibitors include:

• Diarrhea

• Nausea

• Vomiting

• Abdominal pain

• Fatigue

• Metallic taste in the mouth

• Blurred vision

• Ringing in the ears

• Numbness or tingling sensations (paresthesia)

• Increased urination

• Headache

• Burning or local irritation (with topical forms)

Severe side effects of carbonic anhydrase inhibitors include:

• Metabolic acidosis

• Blood cell problems

  • Aplastic anemia

  • Agranulocytosis

• Low potassium levels in the blood

• High calcium levels in the kidneys

• Kidney stones

• Liver damage

Systemic forms of carbonic anhydrase inhibitors (given as tablets or injections) have the potential to cause more side effects than topical forms (given as eye drops). However, side effects are usually mild and temporary. Bicarbonate supplements may be taken to relieve some side effects. All carbonic anhydrase inhibitors are sulfonamide derivatives. They can cause allergic reactions such as rash, itching, photosensitivity, anaphylaxis, and Stevens-Johnson syndrome. People who have had an allergic reaction to sulfonamide drugs in the past should not take carbonic anhydrase inhibitors. Carbonic anhydrase inhibitors can cause metabolic acidosis in nearly 50% of treated patients, including the elderly, people with diabetes, and people with renal disease. Symptoms of metabolic acidosis include fast heartbeat, headache, shallow breathing, vomiting, and confusion.This may not be a complete list of side effects. Consult with a healthcare provider for more information about other side effects of CAIs. 

How much do carbonic anhydrase inhibitors cost?

Carbonic anhydrase inhibitors are available as brand name and generic drugs. Generics are typically less expensive than brand-name versions. The exact cost of your prescription will depend on different factors like the dosage of the medication and insurance coverage. People without insurance or adequate coverage can use other prescription savings options. Using a SingleCare prescription discount card may help reduce the cost of your medications at participating pharmacies.