High-altitude acclimatization occurs in response to decreased oxygen levels. It takes time but improves oxygen transfer and utilization. Adaptations begin quickly and continue improving over days to weeks, then decrease upon returning to sea level. Peak elevation and speed of ascent determine acclimatization success.

Altitude acclimatization is crucial for individuals at 2,500 meters above sea level, influenced by many factors. Medications can help prevent and treat altitude sickness. Understanding the body's responses and mechanisms is key to understanding medication benefits.

Mechanism of Action of Acetazolamide

Acetazolamide acts as a carbonic anhydrase inhibitor, which is a family of metalloenzymes regulated by Zn2+. Carbonic anhydrase is present in many tissues, but acetazolamide acts primarily on the renal tubule and erythrocyte to precipitate its diuretic and H+ secretion function. This drug reduces the proximal renal cell reabsorption of filtered bicarbonate and decreases bicarbonate concentration either in urine or in blood. In the presence of tissues suffering from systemic hypoperfusion, acetazolamide reduces the elevation of plasma lactate levels.

Acetazolamide does substantially more than just breathing more often or more deeply; it speeds up the acclimatization process. At body rest, under acetazolamide treatment, subjects hyperventilate more for the same plasma pCO2, leading to more hypocapnia, but for the same degree of hyperventilation, the hypocapnia can become greater.

The consequence of acetazolamide is to produce renal excretion of bicarbonates, leading to metabolic acidosis. To buffer this acidosis, hyperventilation increases, resulting in what is known as respiratory alkalosis. This mechanism is used to compensate for the body’s disturbance in acid and base balance. Since this is a biological response to maintain acid-base homeostasis, it is known as acclimatization.

The speed of increased breathing induced by acetazolamide raises the O2 uptake at the body level, thereby accelerating the resaturation of haemoglobin, permitting an increase in the oxygen delivery to tissues that is so vitally important in the initial period of acclimatization to high altitude.

Efficacy and Side Effects of Acetazolamide in Altitude Acclimatization

Altitude health-related issues are not only of concern to those working in high-altitude mines but also draw attention from those moving to high altitudes and wishing to acclimatize quickly and develop tolerance to health-related stress. Previous and ongoing studies have demonstrated the effects of acetazolamide in enhancing acclimatization and decreasing acute mountain sickness symptoms, including headache, nausea, and vomiting. However, whether this treatment is necessary in every case is yet to be established. Thus, this review provides information on the effective and safe regimen based on the available literature.

The recommended dosage of acetazolamide medication is 5 mg/kg per day. However, the medication should not be continued for more than 3 days due to associated side effects. In addition, the recommended dose is affected by the severity of the symptoms, time of exposure, altitude of exposure, and age of the individual. These characteristics must be taken into consideration when planning the acetazolamide treatment. The most common adverse effects mentioned in studies are urinary frequency, increased amounts of urine, altered taste, and gastrointestinal side effects.

Serious side effects are extremely rare and occur in 1 in 1000 people. The intensity of these side effects varies from mild to severe degrees that affect daily work patterns, but the majority of serious adverse effects are rarely reported. Therefore, acetazolamide should be used cautiously, and afterwards, the medical status of patients should be evaluated to maximize the benefits of treatment and avoid its adverse effects. The use of acetazolamide should be discontinued in cases of severe intoxication; in addition, these cases should be dealt with as a medical emergency and referred to the emergency department.

Comparison with Other Altitude Acclimatization Strategies

One of the easiest and most practical ways to acclimatize at altitude is to ascend gradually. Another common method is to sleep at a slightly lower elevation than your resting location. Other techniques to help improve physiological stamina at high altitudes may include training and even living at high altitudes. Ascending for a while and then quickly descending to a lower altitude is a strategy.

A third method is the use of drugs. Intensive efforts to improve climatic environments in sports include methods such as enhancing the number of red blood cells, as well as equipment and facilities that improve the atmosphere, introducing behavioural and psychological improvements, and purchasing private estates for self-orientation practice.

Rest/acceptance in the highlands, realized as part of one's planned daily activities in the development phase of altitude training in mid-to-high lands, can enhance natural geographic adjustment by living and working at a high altitude in male adults, thereby improving hydro-sodium activation and dietary access according to custom technology.