From the Guidelines
Acetazolamide's primary mechanism of action is the inhibition of the enzyme carbonic anhydrase, which leads to various systemic effects, including diuretic, anti-glaucoma, and anti-epileptic properties. This inhibition occurs throughout the body but has particularly important effects in the kidneys, where it blocks the reabsorption of bicarbonate, leading to increased bicarbonate excretion and resulting in a metabolic acidosis 1. In the context of treating conditions like idiopathic intracranial hypertension, the dosing of acetazolamide can vary, with a popular starting dose being 250–500 mg twice a day, and the majority of clinicians titrating the daily dose up, with some patients tolerating up to 4 g daily 1. Key effects of acetazolamide include:
- Inhibition of carbonic anhydrase in the kidneys, leading to diuretic effects
- Reduction of aqueous humor production in the eye, lowering intraocular pressure
- Increased cerebral blood flow and reduced cerebrospinal fluid production in the central nervous system
- Potential for various side effects, including increased risk of diarrhea, dysgeusia, fatigue, nausea, paresthesia, tinnitus, vomiting, depression, and rarely renal stones 1. Given the potential side effects, patients should be warned and monitored accordingly, with dosing adjustments made as necessary to balance efficacy and tolerability.
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 The mechanism of action of acetazolamide is through 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
- Diuretic effect due to renal loss of HCO3 ion, which carries out sodium, water, and potassium
- Alteration in ammonia metabolism due to increased reabsorption of ammonia by the renal tubules as a result of urinary alkalinization 2
From the Research
Mechanism of Action of Acetazolamide
The mechanism of action of acetazolamide involves the inhibition of carbonic anhydrase, an enzyme that plays a crucial role in various physiological processes. The key aspects of its mechanism are:
- Inhibition of carbonic anhydrase in the kidneys, resulting in bicarbonaturia and metabolic acidosis 3, 4
- Reduction of bicarbonate and aqueous humor secretion in the eyes, leading to a decrease in intraocular pressure 5
- Acidification of the intracellular and extracellular environments, activating acid-sensing ion channels, which may account for its anti-seizure effects 6
- Modulation of neuroinflammation and attenuation of high-frequency oscillations, contributing to its antiepileptic properties 6
Effects on the Body
The effects of acetazolamide on the body include:
- Diuretic effects, although modest, due to its action as a proximal tubular diuretic 3
- Correction of significant metabolic alkalosis that may occur with loop diuretic therapy 3
- Reduction of intraocular pressure in patients with glaucoma 5, 7
- Improvement in ventilation and sleep quality, which may contribute to its efficacy in preventing and treating acute mountain sickness 4
Therapeutic Applications
Acetazolamide has several therapeutic applications, including:
- Treatment of glaucoma, particularly in cases where other treatments are not effective 5, 7
- Prevention and treatment of acute mountain sickness 4
- Management of epilepsy, although its efficacy and safety need to be further evaluated in randomized controlled trials 6
- Use as a diuretic agent, although its diuretic effects are modest and limited by its transient action and potential for metabolic acidosis 3