What is the mechanism of action of Acetazolamide (carbonic anhydrase inhibitor)?

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From the FDA Drug Label

Acetazolamide is a potent carbonic anhydrase inhibitor, effective in the control of fluid secretion Acetazolamide is an enzyme inhibitor that acts specifically on carbonic anhydrase, the enzyme that catalyzes the reversible reaction involving the hydration of carbon dioxide and the dehydration of carbonic acid Inhibition of carbonic anhydrase in this area appears to retard abnormal, paroxysmal, excessive discharge from central nervous system neurons. The diuretic effect of acetazolamide is due to its action in the kidney on the reversible reaction involving hydration of carbon dioxide and dehydration of carbonic acid

The mechanism of action of acetazolamide is through the inhibition of carbonic anhydrase, an enzyme that catalyzes the reversible reaction of carbon dioxide hydration and carbonic acid dehydration. This inhibition leads to various effects, including:

  • Decreased secretion of aqueous humor in the eye, resulting in a drop in intraocular pressure
  • Retardation of abnormal neuronal discharge in the central nervous system, useful in treating conditions like epilepsy
  • Diuretic effect due to renal loss of HCO3 ion, leading to the loss of sodium, water, and potassium 1

From the Research

Acetazolamide works primarily as a carbonic anhydrase inhibitor, which means it blocks the enzyme carbonic anhydrase that catalyzes the conversion of carbon dioxide and water to carbonic acid, as recently confirmed by 2. This inhibition leads to decreased hydrogen ion secretion in the renal tubules, causing increased sodium, bicarbonate, potassium, and water excretion. The resulting metabolic acidosis and diuresis are responsible for acetazolamide's therapeutic effects. In the eye, it reduces aqueous humor production by inhibiting carbonic anhydrase in the ciliary body, thereby lowering intraocular pressure, which makes it useful for treating glaucoma, as discussed in 3 and 4. In the brain, acetazolamide increases cerebral blood flow and decreases cerebrospinal fluid production, making it effective for altitude sickness, idiopathic intracranial hypertension, and certain types of seizures, as noted in 5 and 6. The drug also affects pH balance in various tissues, which contributes to its diverse clinical applications including as a diuretic, anticonvulsant, and treatment for periodic paralysis and mountain sickness.

Some key points about acetazolamide's mechanism of action include:

  • Inhibition of carbonic anhydrase leads to decreased hydrogen ion secretion in the renal tubules
  • Increased sodium, bicarbonate, potassium, and water excretion due to metabolic acidosis and diuresis
  • Reduction of aqueous humor production in the eye, leading to lowered intraocular pressure
  • Increased cerebral blood flow and decreased cerebrospinal fluid production in the brain
  • Effects on pH balance in various tissues, contributing to its diverse clinical applications

It's worth noting that while acetazolamide has been used for many years, its exact mechanisms of action are still being studied and refined, as seen in the recent review 2. However, its efficacy in treating various conditions, including glaucoma, epilepsy, and altitude sickness, is well established, as discussed in 5, 6, 3, and 4.

Overall, acetazolamide's mechanism of action as a carbonic anhydrase inhibitor is well understood, and its therapeutic effects are widely recognized, as confirmed by the most recent study 2.

References

Research

Evaluating off-label uses of acetazolamide.

American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists, 2018

Research

Acetazolamide: Old drug, new evidence?

Epilepsia open, 2022

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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