Acetazolamide

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Acetazolamide, sold under the trade name Diamox among others, is a medication used to treat glaucoma, epilepsy, acute mountain sickness, periodic paralysis, idiopathic intracranial hypertension (raised brain pressure of unclear cause), heart failure and to alkalinize urine. It may be used long term for the treatment of open angle glaucoma and short term for acute angle closure glaucoma until surgery can be carried out.

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Common side effects include numbness, ringing in the ears, loss of appetite, vomiting, and sleepiness. Acetazolamide is in the diuretic and carbonic anhydrase inhibitor families of medication.

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Acetazolamide came into medical use in 1952. It is on the World Health Organization's List of Essential Medicines. Acetazolamide is available as a generic medication. Ménière's disease, increased intracranial pressure and neuromuscular disorders. A 2012 review and meta-analysis found that there was "limited supporting evidence" but that acetazolamide "may be considered" for the treatment of central (as opposed to obstructive) sleep apnea.

In epilepsy, the main use of acetazolamide is in menstrual-related epilepsy and as an add on to other treatments in refractory epilepsy.

Though various websites on the internet report that acetazolamide can be used to treat dural ectasia in individuals with Marfan syndrome, the only supporting evidence for this assertion exists from a small study of 14 patients which was not peer-reviewed or submitted for publication. Several published cases of intracranial hypotension related to Marfan syndrome would warrant caution in using acetazolamide in these patients unless there is a clear indication, as it could lower intracranial pressure further.

It has also been used to prevent methotrexate-induced kidney damage by alkalinizing the urine, hence speeding up methotrexate excretion by increasing its solubility in urine. There is some evidence to support its use to prevent hemiplegic migraine.

There is tentative evidence it might improve visual snow symptoms for some.

High altitude sickness

Acetazolamide is also used for the treatment of acute mountain sickness. In the prevention or treatment of mountain sickness, acetazolamide inhibits the ability of the kidneys to reabsorb bicarbonate, the conjugate base of carbonic acid. Increasing the amount of bicarbonate excreted in the urine leads to acidification of the blood. Acetazolamide is still effective if started early in the course of mountain sickness. As prevention, it is started one day before travel to altitude and continued for the first two days at altitude.

Pregnancy and lactation

Acetazolamide is pregnancy category B3 in Australia, which means that studies in rats, mice and rabbits in which acetazolamide was given intravenously or orally caused an increased risk of fetal malformations, including defects of the limbs.

Side effects

Common adverse effects of acetazolamide include the following: paraesthesia, fatigue, drowsiness, depression, decreased libido, bitter or metallic taste, nausea, vomiting, abdominal cramps, diarrhea, black stool, polyuria, kidney stones, metabolic acidosis and electrolyte changes (hypokalemia, hyponatremia). Whereas less common adverse effects include Stevens–Johnson syndrome, anaphylaxis and blood dyscrasias.

• Hyperchloremic acidosis
• Hypokalemia (low blood potassium)
• Hyponatremia (low blood sodium)
• Adrenal insufficiency
• Impaired kidney function
• Hypersensitivity to acetazolamide or other sulphonamides.
• Marked liver disease or impairment of liver function, including cirrhosis because of the risk of development of hepatic encephalopathy. Acetazolamide decreases ammonia clearance.

Interactions

It is possible that it might interact with: Carbonic anhydrase is an enzyme found in red blood cells and many other tissues that catalyses the following reaction:

:H₂CO₃ ⇌ H₂O + CO₂

hence lowering blood pH, by means of the following reaction that carbonic acid undergoes:

The mechanism of diuresis involves the proximal tubule of the kidney. The enzyme carbonic anhydrase is found here, allowing the reabsorption of bicarbonate, sodium, and chloride. By inhibiting this enzyme, these ions are excreted, along with excess water, lowering blood pressure, intracranial pressure, and intraocular pressure. A general side effect of carbonic anhydrase inhibitors is loss of potassium due to this function. By excreting bicarbonate, the blood becomes acidic, causing compensatory hyperventilation with deep respiration (Kussmaul breathing), increasing levels of oxygen and decreasing levels of carbon dioxide in the blood.

In the eye this results in a reduction in aqueous humour.

History

An early description of this compound (as 2-acetylamino-1,3,4-thiadiazole-5-sulfonamide) and its synthesis has been patented in 1951.

Research

Smaller clinical trials have also shown promising results in the treatment of normal pressure hydrocephalus (NPH).

Veterinary use

Acetazolamide was originally used as a diuretic but has been largely supplanted by other drugs such as furosemide. Carbonic anhydrase inhibitors are no longer the preferred method of treating intraocular pressure in cases of glaucoma but when a carbonic anhydrase inhibitor is used methazolamide is preferred, although acetazolamide is still used. Acetazolamide is also used to increase the alkalinity of urine to manage urinary calculi, but requires bicarbonate supplementation. In horses it is used as a treatment for hyperkalaemic periodic paralysis.

Acetazolamide has largely been supplanted by other drugs and therapies due to side effects such as hypokalaemia and respiratory acidosis.