Does Acetazolamide Cause Acidosis or Alkalosis? A Pharmacological Analysis

October 13, 2025 •

4 min read

Acetazolamide, a medication often used for conditions like glaucoma and altitude sickness, affects the body's acid-base balance [1, 5]. A key question regarding its use is: does acetazolamide cause acidosis or alkalosis? The answer is rooted in its mechanism of action within the kidneys.

Quick Summary

Acetazolamide causes a hyperchloremic normal anion gap metabolic acidosis. It functions by inhibiting the enzyme carbonic anhydrase in the kidneys, resulting in increased excretion of bicarbonate in the urine and a subsequent decrease in blood pH.

Key Points

Acidosis Effect: Acetazolamide causes hyperchloremic normal anion gap metabolic acidosis [2].
Inhibits Enzyme: It works by inhibiting carbonic anhydrase, primarily in the kidney's proximal tubules [4].
Bicarbonate Loss: This inhibition leads to increased urinary excretion of bicarbonate [4].
Lowered Blood pH: The loss of bicarbonate, a buffer, results in a decrease in blood pH, causing acidosis [4].
Therapeutic Use: The induced acidosis is utilized in treating conditions like altitude sickness [2].
Distinction from Other Diuretics: Unlike acetazolamide, loop and thiazide diuretics generally cause metabolic alkalosis [3].
Monitoring Needed: Monitoring of electrolytes and blood pH is important due to the risk of metabolic acidosis [10].
Avoid in Certain Conditions: It is contraindicated in patients with conditions like severe kidney disease or pre-existing electrolyte imbalances [12].

The Mechanism of Action: How Acetazolamide Impacts Acid-Base Balance

Acetazolamide functions as a carbonic anhydrase inhibitor [4]. Carbonic anhydrase is an enzyme that plays a critical role in various physiological processes, particularly in the kidneys' ability to manage acid-base balance [4]. This enzyme facilitates the conversion of carbon dioxide and water into carbonic acid, which then dissociates into hydrogen ions and bicarbonate ions [4]. This reaction is fundamental for regulating pH in the body.

In the proximal convoluted tubules of the kidneys, carbonic anhydrase is essential for reabsorbing filtered bicarbonate from the glomerular filtrate back into the bloodstream [4]. By inhibiting this enzyme, acetazolamide disrupts this reabsorption process [4]. This leads to an increased amount of bicarbonate being excreted in the urine, a process known as bicarbonaturia [6]. Bicarbonate is a primary buffer in the blood, and its loss results in a decrease in blood pH, causing metabolic acidosis [4]. This specific type of acidosis is often characterized as a normal anion gap, hyperchloremic metabolic acidosis because the kidneys, in an attempt to compensate for the loss of negatively charged bicarbonate, increase the reabsorption of chloride ions [6, 7].

Directly Answering: Acidosis, Not Alkalosis

Therefore, the direct answer to the question does acetazolamide cause acidosis or alkalosis? is that it causes metabolic acidosis [2]. It does not cause alkalosis (an increase in blood pH). Interestingly, due to its ability to induce acidosis, acetazolamide can sometimes be used to manage or treat metabolic alkalosis that might be caused by other medications, such as some diuretics [3]. While a mild level of acidosis is common with long-term use, severe acidosis is less frequent but can occur, especially in individuals with compromised kidney function, the elderly, or those with certain underlying conditions like diabetes [5].

Clinical Applications Related to Induced Acidosis

The effect of acetazolamide on acid-base balance is directly linked to its therapeutic uses:

Glaucoma: In the eye, acetazolamide inhibits carbonic anhydrase in the ciliary body, reducing the production of aqueous humor and thus lowering intraocular pressure [4, 9].
Altitude Sickness: At high altitudes, the body's response to lower oxygen levels often involves hyperventilation, which can lead to respiratory alkalosis. Acetazolamide induces a metabolic acidosis that helps to counteract this alkalosis, stimulating breathing and aiding acclimatization [2, 4].
Edema (Swelling): The diuretic effect stems from the increased excretion of sodium, bicarbonate, and water, which helps to reduce fluid accumulation, particularly in cases related to heart failure [2, 4].
Epilepsy: While the precise mechanism isn't fully clear, the induced acidosis and changes in ion concentrations in the brain are believed to contribute to stabilizing nerve cell activity and potentially reducing seizures [2, 4].
Idiopathic Intracranial Hypertension: This condition involves increased pressure within the skull. Acetazolamide can reduce the production of cerebrospinal fluid by inhibiting carbonic anhydrase in the choroid plexus [2, 4].

Contrasting Acetazolamide with Other Diuretics

To further clarify acetazolamide's impact, comparing it to other types of diuretics is helpful. Loop diuretics (like furosemide) and thiazide diuretics (like hydrochlorothiazide) act on different segments of the nephron and typically result in metabolic alkalosis. This occurs because they increase the excretion of chloride, sodium, and potassium, leading to a relative increase in serum bicarbonate levels [3].


Feature	Acetazolamide (Carbonic Anhydrase Inhibitor)	Loop Diuretics (e.g., Furosemide)	Thiazide Diuretics (e.g., Hydrochlorothiazide)
Primary Site of Action	Proximal Convoluted Tubule [4]	Thick Ascending Limb of Loop of Henle	Distal Convoluted Tubule
Main Ions Excreted	Bicarbonate (HCO3-), Sodium (Na+), Potassium (K+) [4]	Sodium (Na+), Potassium (K+), Chloride (Cl-)	Sodium (Na+), Chloride (Cl-), Potassium (K+)
Effect on Acid-Base Balance	Metabolic Acidosis [2]	Metabolic Alkalosis [3]	Metabolic Alkalosis [3]
Effect on Serum Chloride	Increases (Hyperchloremic) [6]	Decreases (Hypochloremic)	Decreases (Hypochloremic)

Potential Risks, Monitoring, and Contraindications

Despite its benefits, acetazolamide can have side effects. Common ones include tingling sensations (paresthesias), fatigue, a metallic taste, and digestive issues [11]. More significant risks include:

Metabolic Acidosis: Regular monitoring of blood electrolytes and pH is advisable, particularly for vulnerable individuals [10]. In cases of overdose or in susceptible patients, acidosis can become severe [5, 8]. Treatment typically involves supportive care and sometimes administering bicarbonate [8].
Electrolyte Imbalances: Levels of potassium (hypokalemia) and sodium (hyponatremia) can decrease and should be monitored [10].
Kidney Stone Formation: Long-term use of acetazolamide can increase the likelihood of developing calcium phosphate kidney stones [4].
Allergic Reactions: As it is a derivative of sulfonamides, acetazolamide can trigger severe allergic responses, such as Stevens-Johnson syndrome, in individuals with a known sulfa allergy [10].

Acetazolamide should be avoided in patients who already have low sodium or potassium levels, hyperchloremic acidosis, severe kidney or liver disease (especially cirrhosis), and adrenal gland insufficiency [12].

Conclusion

Acetazolamide's primary effect on the body's acid-base balance is the induction of metabolic acidosis. This is a direct consequence of its action as a carbonic anhydrase inhibitor in the kidneys, leading to increased bicarbonate excretion. This mechanism is central to its therapeutic effects in various conditions and distinguishes it from many other diuretics. Awareness of this effect and the potential for metabolic acidosis is crucial for the safe and effective clinical use of acetazolamide.

For further details on the pharmacology and clinical use of acetazolamide, consult the NCBI StatPearls publication.

Frequently Asked Questions

Acetazolamide leads to metabolic acidosis. Its mechanism of action causes the kidneys to excrete more bicarbonate, which is a base, thus lowering blood pH [2, 4].

The primary reason is that acetazolamide inhibits carbonic anhydrase in the kidneys, preventing the reabsorption of bicarbonate from the filtrate back into the blood. This loss of bicarbonate causes the blood to become more acidic [4].

Yes, acetazolamide is sometimes used to treat metabolic alkalosis, particularly when it's caused by other diuretics. It promotes bicarbonate excretion, which helps to normalize blood pH [3].

It is typically associated with a hyperchloremic, normal anion gap metabolic acidosis. The body compensates for bicarbonate loss by increasing chloride reabsorption [6, 7].

While often mild and tolerable, severe and potentially life-threatening acidosis is possible, especially in individuals with impaired kidney function or with overdose. Regular monitoring helps to manage this risk [5, 8].

Common uses include the treatment of glaucoma, prevention and management of acute mountain sickness, managing edema associated with heart failure, and as an adjunctive treatment for certain forms of epilepsy and idiopathic intracranial hypertension [2, 9].

Monitoring serum electrolytes, particularly potassium and sodium, and blood pH is important to detect metabolic acidosis and other imbalances. A baseline complete blood count is also often recommended [10].