Typical symptoms of acute mountain sickness (AMS) are headache, loss of appetite, disturbed sleep, nausea, vomiting, fatigue, and dizziness. However, more serious conditions such as high altitude pulmonary edema (HAPE) or cerebral edema (HACE) can present with this illness. Avoiding these unpleasant symptoms while at elevatione is possible through gradual pre-acclimatization when possible (what science recommends!), or there are specific medications that can potentially prevent the development of AMS, such as acetazolamide. This article will address how acetazolamide (also known as Diamox) can help prevent AMS, discuss the physiological effects of the medication, some side effects, and whether or not this drug can enhance physical performance.

 How does it work?

Acetazolamide is a carbonic anhydrase inhibitor. Carbonic anhydrase regulates kidney absorption of sodium bicarb and chloride. Acetazolamide works by inhibiting carbonic anhydrase, preventing the reabsorption of sodium bicarb and chloride, causing acidosis in the blood. When experiencing AMS, the body is in a state of respiratory alkalosis. By taking acetazolamide, which causes metabolic acidosis it drives receptors in the body to increase the patient’s minute ventilation by as much as 50%, improving arterial PO2 and increasing oxygen saturation.

How can I obtain acetazolamide and when should I start taking it?

Acetazolamide requires a doctor’s prescription, and the typical dose for the prevention of AMS is 125 mg twice daily. The typical recommendation is to start taking acetazolamide one day before your exposure to high altitude and continue usage throughout your trip. When taken one day before exposure, studies show that acetazolamide reduced AMS incidence and enhanced tolerance to submaximal exercise on the first day at high altitude versus starting administration the day of arrival.² However, if, for some reason, the medication isn’t started a day before arrival to high altitude, then the medication should be started upon arrival, which still shows a decreased incidence in the development of AMS. 

Allergies & Side Effects

Acetazolamide belongs to a classification of drugs known as sulfonamides, which is broken down further into two categories: antibiotics and nonantibiotics. Acetazolamide is considered a nonantibiotic sulfonamide, which varies significantly from sulfonamide antibiotics because these antibiotics contain what is known as an arylamine group in their chemical structure. This arylamine group is a key component of the allergic response to sulfonamide antibiotics (sulfamethoxazole, sulfasalazine, sulfadiazine, and the anti-retrovirals amprenavir and fosamprenavir); however, this structure is not present in other sulfonamide drugs like acetazolamide.¹ There is available evidence that suggests patients who are allergic to arylamine sulfonamides do not cross-react to sulfonamides that lack the arylamine group and so may safely take non-arylamine sulfonamides.¹ Patients with known allergies to sulfonamide drugs should consult with their healthcare provider before taking acetazolamide.

Like all other medications, there are risks that side effects will occur with acetazolamide’s administration. The common side effects are fatigue, malaise, changes in taste, paresthesia, diarrhea, electrolyte disorders, polyuria, and tinnitus. While conducting research, I found 3 – 4 people from my hometown, located at 69 feet above sea level, who have taken acetazolamide while rapidly ascending to 8,000+ feet to ski or hunt. When asked how their experience was taking acetazolamide, the common response was that they stopped using it within the first two days due to the change in the taste of their beer! The pleasurable “fizz” in our carbonated drinks is attributed to chemical excitation of nociceptors in the oral cavity via the conversion of CO2 to the carbonic acid in a reaction catalyzed by carbonic anhydrase. So administering a carbonic anhydrase inhibitor like acetazolamide results in flat-tasting carbonated drinks, or, as described by the aforementioned subjects, a “nasty beer”!⁴ While a bad tasting beer is no fun, AMS is a lot less fun, and one would be best advised to continue taking acetazolamide while at high altitude.

Can taking acetazolamide increase physical performance and endurance at high altitudes?

Though enticing, it doesn’t seem to work out that way. There are multiple studies on exercise endurance in hypoxic conditions with the administration of acetazolamide, but the produced results are confounding. The majority of the studies show that for a non-acclimated person taking acetazolamide in hypoxic conditions, endurance and exhaustion time were increased with submaximal and maximal exercise. A few reasons this may be true are the induction of metabolic acidosis and its effects on muscle cells, the diuretic effect of the drug inducing dehydration, and additional increases in work of breathing cause vasoconstriction in locomotor muscles, which can impair exercise performance.³ Regardless, this medication’s proven science in the prevention of AMS should not be mistaken with the multiple confounding studies on exercise endurance.

From Opelousas, Louisiana, Scott Rogers is currently a Family Nurse Practitioner student at Walden University after having practiced five years as an RN following his BSN from the University of Louisiana at Lafayette. He has lived in Colorado for the past four years where he enjoys hiking with his wife and dog, snowboarding all the resorts in Summit County, and basketball, and hopes to pursue more work with acute physical rehabilitation, orthopedics, and sports medicine.

References

1. American Academy of Allergy Asthma & Immunology. (2019, June 23). Acetazolamide and sulfonamide allergy: AAAAI. Retrieved November 13, 2020, from https://www.aaaai.org/ask-the-expert/acetazolamide

2. Burtscher, M., Gatterer, H., Faulhaber, M., & Burtscher, J. (2014). Acetazolamide pre-treatment before ascending to high altitudes: when to start?. International journal of clinical and experimental medicine, 7(11), 4378–4383.

3. Garske, L., Medicine, 1., Brown, M., Morrison, S., Y, B., G., B., . . . Zoll, J. (2003, March 01). Acetazolamide reduces exercise capacity and increases leg fatigue under hypoxic conditions. Retrieved November 13, 2020, from https://journals.physiology.org/doi/full/10.1152/japplphysiol.00746.2001

4. Jean-Marc Dessirier, Christopher T. Simons, Mirela Iodi Carstens, Michael O’Mahony, E. Carstens, Psychophysical and Neurobiological Evidence that the Oral Sensation Elicited by Carbonated Water is of Chemogenic Origin, Chemical Senses, Volume 25, Issue 3, June 2000, Pages 277–284, https://doi.org/10.1093/chemse/25.3.277