Acetazolamide was developed by Lederle Laboratories and introduced in the early 1950s. It was initially used to treat epilepsy in 1950 and later approved for glaucoma in 1954. As the first carbonic anhydrase inhibitor and diuretic, its development marked a significant advancement in therapeutic options. Early research by Bernard Becker and colleagues demonstrated its ability to lower intraocular pressure in glaucoma by decreasing the production of aqueous humor. As a carbonic anhydrase inhibitor, acetazolamide works by blocking the enzyme carbonic anhydrase, which plays a key role in the regulation of acid-base balance and fluid secretion in various tissues, including the eyes, kidneys, and central nervous system. This mechanism contributes to its diuretic, antiglaucoma, anticonvulsant, and altitude sickness–relieving effects.
Brand Names
This medication helps your body produce more urine, allowing it to remove excess salt and water. It is used to treat seizures, certain forms of glaucoma, and to prevent symptoms of altitude sickness. It is commonly known by the brand name Diamox.
Mechanism of Action
Acetazolamide works as an anticonvulsant by directly blocking the enzyme carbonic anhydrase in the brain. This action helps reduce carbon dioxide levels in the lungs, which in turn increases the amount of oxygen in the blood—potentially helping to control seizures. As a diuretic, it also blocks carbonic anhydrase in the kidneys. This reduces the number of hydrogen ions available for fluid reabsorption, leading to the production of more alkaline (less acidic) urine. As a result, the body gets rid of more bicarbonate, sodium, potassium, and water through urine, helping to reduce fluid build-up.
Pharmacokinetics:
Absorption:
Acetazolamide is quickly and almost fully absorbed when taken by mouth, with peak levels in the blood reached within 2 to 4 hours after dosing. It has a high bioavailability of over 90%. Absorption takes place in the stomach and upper part of the intestine, and food does not significantly affect how well it is absorbed.
Distribution:
Acetazolamide is a carbonic anhydrase inhibitor with a volume of distribution of about 0.3 L/kg. It is highly bound to plasma proteins (around 95%) and is not metabolized by the body.
Metabolism:
Acetazolamide is minimally metabolized in the body and is mainly excreted unchanged by the kidneys through active tubular secretion.
Excretion:
Acetazolamide is mainly eliminated unchanged through the kidneys by active tubular secretion, with little to no significant metabolism.
PHARMACODYNAMICS
Acetazolamide is a powerful carbonic anhydrase inhibitor used to manage fluid secretion, treat certain seizure disorders, and promote diuresis in cases of abnormal fluid build-up. Unlike mercurial diuretics, acetazolamide is a nonbacteriostatic sulfonamide with a unique chemical structure and pharmacological profile that sets it apart from traditional bacteriostatic sulfonamides.
ADMINISTRATION
Acetazolamide can be given orally in the form of tablets or capsules, or administered intravenously, depending on the medical condition being treated. Dosage and usage instructions can vary significantly, so it’s important to follow your doctor’s guidance closely.
DOSAGE
The dosage of acetazolamide varies depending on the condition being treated, the patient’s individual needs, and overall health. For glaucoma, the typical dose ranges from 250 mg to 1,000 mg per day, divided into multiple doses, with the exact amount determined by the healthcare provider based on the patient’s response. To prevent altitude sickness, a common recommendation is 125 mg to 250 mg taken twice daily, starting one to two days before ascent and continuing for about 48 hours or until descent. For seizure management, the dose usually falls between 250 mg and 1,000 mg per day, divided into one or more doses as prescribed. It is important to follow the doctor’s instructions carefully to ensure safe and effective treatment.
DRUG INTERACTIONS
While some medications should never be used together, there are situations where two drugs may be combined even if an interaction is possible. In such cases, your doctor may adjust the dosage or take other precautions to ensure your safety. If you are taking this medicine, it is especially important to inform your healthcare provider about any other medications you are using. The following list highlights potential interactions based on their clinical importance, but it may not include all possible interactions.
FOOD INTERACTIONS
While there are no major contraindications regarding food and acetazolamide, you should be mindful of certain dietary factors and substances that can affect the medication's effectiveness and side effects.
CONTRAINDICATIONS
Acetazolamide is a carbonic anhydrase inhibitor commonly used to treat glaucoma, epilepsy, edema, and altitude sickness. However, it is not recommended for individuals with certain medical conditions because of the potential for serious side effects.
SIDE EFFECTS
Allergic reactions: Symptoms may include skin rash, itching, hives, and swelling of the face, lips, tongue, or throat.
Aplastic anemia: Signs include unusual weakness or fatigue, dizziness, headache, difficulty breathing, and increased bleeding or bruising.
High acid levels: May cause trouble breathing, weakness, confusion, headache, rapid or irregular heartbeat, nausea, and vomiting.
Infection: Look out for fever, chills, cough, or sore throat.
Kidney stones: Symptoms include blood in the urine, pain or difficulty passing urine, and pain in the lower back or sides.
TOXICITY
Acetazolamide toxicity can affect the central nervous system, causing symptoms such as fatigue, confusion, lethargy, and even coma. It may also lead to metabolic disturbances like hyperchloremic metabolic acidosis and imbalances in electrolytes. The risk of toxicity is higher in patients with impaired kidney function due to drug build-up, but it can also result from high doses or drug interactions
