Acetazolamide, sold under the trade name Diamox, is a carbonic anhydrase inhibitor that is used to treat glaucoma, epileptic seizures, benign intracranial hypertension (pseudotumor cerebri), altitude sickness, cystinuria, and dural ectasia. Acetazolamide is available as a generic drug and is also used as a diuretic.

Mechanism of Action

This drug will block the formation of H+ and H2CO3 from CO2 and H2O. The end result is that bicarbonate is excreted in the urine. Indirectly, it will block the Na/H exchanger in the renal proximal tubule by decreasing the conversion of intracellular CO2 and H2O into bicarbonate and a hydrogen ion that is needed for the Na/H exchanger to reabsorb sodium (and water) back from the tubule lumen. Therefore, there is a natriuretic/diuretic action in addition to the "washing away" of bicarbonate in the urine. The excess luminal water and sodium leads to an increased flow rate that can further disrupt other transporters in the tubule from functioning properly.

Uses

Acetazolamide is often used in the treatment of various diseases. For glaucoma sufferers, the drug decreases fluid formation in the eye resulting in lower intraocular pressure. In epilepsy, its main use is in absence seizures, with some benefit in other seizure syndromes. It is also used to decrease generation of cerebrospinal fluid in benign intracranial hypertension and has shown efficacy in autosomal dominant hyperkalemic periodic paralysis. It's been demonstrated in drug trials to relieve symptoms associated with dural ectasia in indivduals with Marfan Syndrome. Off-label uses include Acetazolamide as a conjunction drug to merely assist patients with sleep apnea by lowering blood pH and encourage respiration.

Acute mountain sickness

Acetazolamide is sometimes taken prophylactically, anywhere between 125 milligrams (mg) to 500 mg per day, starting a few days before going to the higher altitude. Such use is recommended for those ascending from sea level to 3000 meters (9800 feet) in one day, or for those ascending more than 600 meters (2000 feet) per day once above an altitude of 2500 meters (8200 feet). Also, prophylactic use is recommended for those with a significant history of acute mountain sickness.

The drug forces the kidneys to excrete bicarbonate, the conjugate base of carbonic acid. By increasing the amount of bicarbonate excreted in the urine, the blood becomes more acidic. Acidifying the blood stimulates ventilation, which is beneficial during acclimatization.

Note that acetazolamide is not an immediate fix for acute mountain sickness; it speeds up acclimatization which in turn helps to relieve symptoms. This may take up to a day or two, and requires waiting without any further rapid ascent. It is often advisable to descend if even mild acute mountain sickness is experienced. If serious sickness is encountered, descent is considered mandatory unless other circumstances present greater danger.

Side-effects

Common side effects of using this drug include numbness and tingling in the fingers and toes, and taste alterations (parageusia), especially for carbonated drinks; both are usually due to mild hypokalemia (low potassium levels). Some may also experience blurred vision but this usually disappears shortly after stopping the medication. Acetazolamide also increases the risk of developing calcium oxalate and calcium phosphate kidney stones. Everyone will experience more frequent urination as a result of using acetazolamide. One should drink more fluids than usual to prevent dehydration and headaches. Acetazolamide prolongs the effects of amphetamines and related drugs.

Contraindications

Acetazolamide should not be taken by individuals if:

• They have sickle cell anemia
• They are allergic to sulfa medications
• They are allergic to any carbonic anhydrase inhibitor
• They have liver or kidney disease
• They have adrenal gland failure (i.e. Addison's disease)
• They have diabetes
• They are pregnant or nursing mothers

References

• Houston, Charles S. (2005). Going Higher: Oxygen Man and Mountains. Seattle, WA: Mountaineers Books.
• Griffen, H. Winter (1989). Complete Guide to Prescription & Non-Prescription Drugs. Putnam Adult.
• Dietz T.E. An Altitude Tutorial. International Society for Mountain Medicine. Retrieved on 2007-11-15..
• Diamox - Quoted from the Physician's Desk Reference 1993. Climber.org. Retrieved on 2007-11-15..

• Ferrer S, Borras J, Martin-Gil J, Martín-Gil FJ.(1989). "Thermal studies on sulfonamide derivative complexes .1. Thermal-behavior of Acetazolamide – Copper complexes". Thermochim Acta, 147(2):321-330.

Footnotes