Acetazolamide

Alpha Glycosidase Inhibitor

 

Attributes

Pregnancy B3

 

Other Contra-Indication

Taking acetazolamide with primidone, phenytoin or phenobarbitone over the long term can increase the risk of bone disease caused by a thinning of bone structure

 

Class Contra-Indication

Our Records are Incomplete for Drug Class Contra-Indications

Acetazolamide

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 is a carbonic anhydrase inhibitor.

Carbonic anhydrase (CA) catalyzes the forward motion of molecules in the following equation:

CO₂ + H₂O >> ^CA >> H₂CO₃ >> H⁺ + HCO₃

where CA converts carbon dioxide (CO₂) and water (H₂O) to carbonic acid (H₂CO₃), which then dissociates to a hydrogen ion (H⁺, an acidic proton), and a bicarbonate ion (HCO₃^-, a basic anion). In some tissues (particularly plants), the equilibrium is such that CA can catalyze the reverse direction of the reaction. Carbonic acid inhibitors, such as acetazolamide, inhibit CA in tissue and fluid, causing less movement of carbonic acid toward CO₂ production. In the kidneys, blocking CA leads to bicarbonate wasting in the tubules (alkalizes urine), loss of bicarbonate subsequently leads to a metabolic acidosis. In the meantime, H⁺ backs up due to acetazolamide CA inhibition in the tubule and enters the cell with Cl^-, then passes into the bloodstream, creating a hyperchloremic metabolic acidosis.^[1] This effect can also be used for therapeutic correction of respiratory alkalosis.

Uses

Acetazolamide is often used in the treatment of various diseases.

Glaucoma

It has been used for glaucoma sufferers.^[2] The drug decreases fluid formation in the eye resulting in lower intraocular pressure.

Neurologic

In epilepsy, its main use is in absence seizures and myoclonic seizures.^[3]. It can be used in both episodic ataxia types 1 and 2 (although the mechanisms are presumed to be different between the two).

It is also used to decrease generation of cerebrospinal fluid in idiopathic intracranial hypertension^[4] and has shown efficacy in some forms of hyperkalemic periodic paralysis.^[5]

Marfan syndrome

It's been demonstrated in drug trials to relieve symptoms associated with dural ectasia in individuals with Marfan Syndrome.^[6]

Sleep apnea

Off-label uses include acetazolamide as a conjunction drug to merely assist patients with sleep apnea by lowering blood pH and encourage respiration.^[7]

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).^[8][9] 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.^[9] Acidifying the blood stimulates ventilation, which increases the amount of oxygen in the blood.^[10][11]

Note that acetazolamide is not an immediate fix for acute mountain sickness; it speeds up part of the acclimatization process which in turn helps to relieve symptoms.^[12][13] 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. 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. Acetazolamide also causes metabolic acidosis.

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 are pregnant or nursing mothers

References

1. ^ Renal and Electrolyte Disorders Schrier 1976: page 89
2. ^ Kaur IP, Smitha R, Aggarwal D, Kapil M (November 2002). "Acetazolamide: future perspective in topical glaucoma therapeutics". Int J Pharm 248 (1-2): 1–14. doi:10.1016/S0378-5173(02)00438-6. PMID 12429455. http://linkinghub.elsevier.com/retrieve/pii/S0378517302004386. 
3. ^ "Treatment of Epilepsy | Comprehensive Epilepsy Center | NYU Medical Center, New York, NY". http://www.med.nyu.edu/cec/treatment/medications/side_effects/aceta.html. Retrieved 2008-12-19. 
4. ^ Celebisoy N, Gökçay F, Sirin H, Akyürekli O (November 2007). "Treatment of idiopathic intracranial hypertension: topiramate vs acetazolamide, an open-label study". Acta Neurol. Scand. 116 (5): 322–7. doi:10.1111/j.1600-0404.2007.00905.x. PMID 17922725. http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0001-6314&date=2007&volume=116&issue=5&spage=322. 
5. ^ Ptáĉek LJ, Tawil R, Griggs RC, et al. (August 1994). "Sodium channel mutations in acetazolamide-responsive myotonia congenita, paramyotonia congenita, and hyperkalemic periodic paralysis". Neurology 44 (8): 1500–3. PMID 8058156. 
6. ^ Scoliosis Research Society (2006-11-27). "Dural Ectasia in the Marfan Spine: Symptoms and Treatment.also it's been used in high-altitude mountain sickness". SpineUniverse. http://www.spineuniverse.com/displayarticle.php/article922.html. Retrieved 2007-11-15. 
7. ^ Arch Intern Med - Abstract: Central sleep apnea. Improvement with acetazolamide therapy, October 1, 1982, White et al. 142 (10): 1816
8. ^ Hackett, P.H. & Roach, R.C. (2001). "High-altitude illness". The New England Journal of Medicine 345 (2): 107–114. doi:10.1056/NEJM200107123450206. PMID 11450659. 
9. ^ ^{a b} Fulco, CS; Ditzler, D; Soares, R; Lammi, E; Muza, SR; Degroot, DW (2002). "Effect of Acetazolamide on Isolated Quadriceps Muscle Endurance Performance at Sea Level and During Acute Altitude Exposure". US Army Research Inst. Of Environmental Medicine Thermal and Mountain Medicine Division Technical Report (USARIEM-TR-T02/9). http://archive.rubicon-foundation.org/7602. Retrieved 2008-09-30. 
10. ^ title=Altitude.org |year=2004 |url=http://www.altitude.org |accessdate=2009-06-05 }}
11. ^ Leaf DE, Goldfarb DS (April 2007). "Mechanisms of action of acetazolamide in the prophylaxis and treatment of acute mountain sickness". J. Appl. Physiol. 102 (4): 1313–22. doi:10.1152/japplphysiol.01572.2005. PMID 17023566. 
12. ^ Muza, SR; Fulco, CS; Cymerman, A (2004). "Altitude Acclimatization Guide.". US Army Research Inst. Of Environmental Medicine Thermal and Mountain Medicine Division Technical Report (USARIEM-TN-04-05). http://archive.rubicon-foundation.org/7616. Retrieved 2009-03-05. 
13. ^ Cymerman, A; Rock, PB. Medical Problems in High Mountain Environments. A Handbook for Medical Officers. USARIEM-TN94-2. US Army Research Inst. of Environmental Medicine Thermal and Mountain Medicine Division Technical Report. http://archive.rubicon-foundation.org/7976. Retrieved 2009-03-05