Using Drugs to Climb Mount Everest: Cheating or Life-saving Necessity?

Using Drugs to Climb Mount Everest: Cheating or Life-saving Necessity?

The world of sport has been corrupted by drugs as far back as ancient Greece (Kamber 2011; Landry and Kokotailo 1994). It was only within the last century that actions have been taken against the use of performance enhancing drugs to gain unfair advantages (Reardon and Creado 2014; Li and Zhang 2018); known as ‘doping’ by many enthusiasts. When it comes to mountain climbing however, there is still a mass debate over what exactly counts (Wagner 2012), since the harsh conditions athletes face at high altitudes pose significant risks that cannot go unnoticed. Regardless, drug use remains prevalent amongst the growing community of climbers (Donegani et al. 2016); emphasised by the ease at which drugs can be obtained in developing countries (Cushing et al. 2012). Most high altitude climbers are known to use diuretics (Havryliuk et al. 2015), while other classes of drugs that are uncommonly used consist of: glucocorticoids, calcium channel blockers, phosphodiesterase inhibitors, etc. (Luks et al. 2016). The choice of drug is important, as each has its own mechanism of action against certain conditions, but will also come with adverse effects to look out for.

Examples of Drugs Used by Climbers

Acetazolamide

Acetazolamide is used in the prevention and treatment of acute mountain sickness (AMS), and also in the prevention of high-altitude cerebral and pulmonary oedema (HACO/HAPO; Luks et al. 2014); advanced forms of AMS that leads to swelling (Medhi et al. 2018; CITATION for pulmonary). Being classed as a diuretic (Basnyat et al. 2003); more specifically a carbonic anhydrase (CA) inhibitor, acetazolamide predominantly acts within the proximal convoluted tubule of the nephron (De Marchi and Cecchin 1990).

Get Help With Your Essay

If you need assistance with writing your essay, our professional essay writing service is here to help!
Find out more about our Essay Writing Service

Inhibition of CA isoforms ultimately decreases reabsorption of bicarbonate into the blood and increases its excretion (Tsuruoka et al. 2001), giving rise to the accumulation of acids within the blood (Swenson 1984); otherwise known as metabolic acidosis (see Figure 1 for mechanism). Metabolic acidosis is important, as at high altitudes a degree of hypoxia (oxygen deficiency within tissues) would be experienced from decreases in the partial pressure of atmospheric oxygen (Zafren 2013; Wang et al. 2018). A long known response to hypoxia is to increase the minute ventilation rate of the lungs (Gesell et al. 1940), which in turn prompts a rise in the pH of the blood via the partial pressure decrease of arterial carbon dioxide (i.e. respiratory alkalosis [Swenson 1984]). Respiratory alkalosis is inhibitory (Küpper et al. 2008), limiting further increases in ventilation (a factor that is said to drive the symptoms of AMS [Hall et al. 1965; ANOTHER CITATION]). The metabolic acidosis induced by acetazolamide essentially cancels out the effects of respiratory alkalosis (Bell and Haouzi 2009), to speed up acclimatisation in the alleviation of AMS (Lipman et al. 2018; Zafren 2013). While this mechanism is currently the most accepted, it has also been deemed ‘unsatisfactory’ in explaining the treatment of AMS alone (Leaf and Goldfarb 2007); since proven to also rely on secondary mechanisms that are not as well connected (CITATIONS).  

Figure 1. The Mechanism of Action of Acetazolamide in the Treatment of Acute Mountain Sickness.      AMS = Acute Mountain Sickness, PO₂ = Partial Pressure of Atmospheric Oxygen, P_aCO₂ = Partial Pressure of Arterial Carbon Dioxide, CA = Carbonic Anhydrase, Purple Circle (    ) = Acetazolamide, Orange Oval (     ) = Na⁺/H⁺ Antiporter (NHE-3), PCT = Proximal Convoluted Tubule. Arrows with a red minus next to them are pathways that are inhibited by acetazolamide. Arrows with a plus next to them are pathways induced by acetazolamide. The blue dashed line protruding from CA indicates the processes normally catalysed by carbonic anhydrase isoforms (Adapted from Leaf and Goldfarb 2007; Petrovic and DuBose 2013. Created with further information from Tsuruoka et al. 2001).

The use of CA inhibitors will also come with possible adverse effects, including: hypokalaemia (Spaeth 1967), hyperchloremia (Walmsley and White 1985), skin rashes (due to allergic reactions towards the presence of the sulphonamide group; Kelly and Hackett 2010) and alkalinisation of the urine (leading to decreased ammonia excretion and the precipitation of kidney stones; Owen et al. 1960; Paisley and Tomson 1999). Metabolic acidosis can be an adverse effect (Maisey and Brown 1981), but not as much in this case.

Dexamethasone

In the subject of high altitude climbing, dexamethasone has been suggested to mainly have use in treating HACO (Citation); while also treating and preventing symptoms of AMS. The exact cause of HACO is currently unknown, however there is evidence to suggest the swelling is mostly a result of the increased permeability of the blood-brain barrier (BBB; Marussi et al. 2017; Sagoo et al. 2017). It has been thought that vascular endothelial growth factors (VEGFs) are mainly responsible for this permeability (Jiang et al. 2014; Li et al. 2014), as they have been observed to increase after brain injuries (Hirose et al. 2013; Shore et al. 2004; Thou-Zuchman et al. 2010). VEGFs induce this effect by disrupting the proteins that are involved in tight-junction formation (Argaw et al. 2009), thereby resulting in gaps between endothelial cells of the blood vessels.

The mechanism of dexamethasone in the treatment of HACO is also not entirely known either, however is said to combat the above by down regulating; or in other words, decreasing cellular quantities of VEGFs (Hyongbum et al. 2008). Furthermore, dexamethasone can also increase levels of angiopoietin-1, ZO-1 and occludin (Hyongbum et al. 2008; Romero et al. 2003); proteins that are known to stabilise the BBB and induce tight junction formation (Augustin et al. 2009; Lee 2015; Thurston et al. 2000). Dexamethasone is classed as a glucocorticoid (Donegani et al. 2016); the glucocorticoid receptor (often referred to as a ‘Class 1 nuclear receptor’ [citations]) being present in various types of cells (citations). It is the activation of this receptor that regulates the levels of the proteins mentioned (Hue et al. 2015; Hyongbum et al. 2008); in a pathway that can be visualised in Figure 2.

While dexamethasone decreases the effects of HACO, it can also be responsible for inducing unwanted effects that may involve: Increases in blood pressure and sugar levels (Bernal-Mizrachi et al. 2003; Perez et al. 2014), muscle and bone loss (Hasselgren et al. 2010; Klein 2015), glaucoma (Jones and Rhee 2006), gains in appetite (via increases in leptin levels; Miell et al. 1996), and multiple others (Beule et al. 2008; El Abd et al. 2015; Vardy et al. 2006). 

Nifedipine 235

Sildenafil 235

The Ethics of Doping

Drug use comes with an extensive list of ethical pros and cons (CITATIONS); however (to be brief), only a few will be discussed here. The most popular argument against doping seems to be that unfair advantages are gained over those who don’t take any drugs (CITATIONS). Counterarguments to this can well be made; an obvious one being the array of health benefits athletes receive. Our bodies were never designed to withstand conditions at high altitudes, therefore protective measures are vital to ensure the safety of athletes. This is often said to be in accordance with the ‘duty of care’ associations must legally abide by (CITATION).

 Another valid argument is that athletes commonly act as role models towards the majority of younger athletes. Adolescents are often thought to be more impressionable overall (CITATION), so learning their favourite climber is involved in drug use may influence them to do the same. This could lead to serious harm, as a teenager is likely to disregard a drug’s adverse effects in the pursuit of success (CITATION, maybe?).  

Conclusion

The use of specific drugs by high altitude climbers can absolutely be described as a crucial measure in combatting the effects brought about by high altitudes. For this reason alone, it is clear why there is a significant amount of doping to be witnessed in the growing community of Everest climbers. When it comes to passing judgement however, there are numerous ethical and medical aspects to be considered; making it difficult for proper decisions to take place anytime soon within the competitive scene. Ultimately, Minds should therefore be made up on the basis that the benefits of taking the drug will outweigh the possible adverse effects towards themselves and other parties… but we don’t live in a perfect world.

Word Count:

References

• Augustin, H. G., Koh, G. Y., Thurston, G. and Alitalo, K. (2009). Control of vascular morphogenesis and homeostasis through the angiopoietin-Tie system. Nature Reviews. Molecular Cell Biology 10(3):165-177.
• Basnyat, B., Gertsch, J. H., Johnson, W., Castro-Marin, F., Inoue, Y. and Yeh, C. (2003). Efficacy of Low-dose Acetazolamide (125 mg BID) for the Prophylaxis of Acute Mountain Sickness: A Prospective, Double-blind, Randomized, Placebo-controlled Trial. High Altitude Medicine & Biology 4(1):45-52.
• Bell, H. J. and Haouzi, P. (2009). Acetazolamide suppresses the prevalence of augmented breaths during exposure to hypoxia. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology 297(2):R370-R381.
• Bernal-Mizrachi, C., Weng, S., Feng, C., Finck, B. N., Knutsen, R. H., Leone, T. C., … Semenkovich, C. F. Dexamethasone induction of hypertension and diabetes is PPAR-α dependent in LDL receptor–null mice. Nature Medicine 9(8):1069-1075.
• Beule, A. G., Scharf, C., Biebler, K., Göpferich, A., Steinmeier, E., Wolf, E., … Kaftan, H. (2008). Effects of Topically Applied Dexamethasone on Mucosal Wound Healing Using a Drug-Releasing Stent. The Laryngoscope 118(11):2073-2077.
• Cushing, T. A., McIntosh, S. E., Keyes, L. E., Rodway, G. W., Schoene, R. B., Basnyat, B. and Freer, L. (2012). Performance-Enhancing Drugs—Commentaries. Wilderness & Environmental Medicine 23(3):207-211.
• De Marchi, S. and Cecchin, E. (1990). Severe metabolic acidosis and disturbances of calcium metabolism induced by acetazolamide in patients on haemodialysis. Clinical Science 78(3):295-302.
• Donegani, E., Paal, P., Küpper, T., Hefti, U., Basnyat, B., Carceller, A., … Hillebrandt, D. (2016). Drug Use and Misuse in the Mountains. An UIAA MedCom Consensus Guide for Medical Professionals. High Altitude Medicine & Biology 17(3):157-184.
• El Abd, O. H., Amadera, J., Pimentel, D. and Gomba, L. (2015). Immediate and Acute Adverse Effects Following Transforaminal Epidural Steroid Injections with Dexamethasone. Pain Physician 18(3):277-286.
• Gesell, R., Lapides, J. and Levin, M. (1940). THE INTERACTION OF CENTRAL AND PERIPHERAL CHEMICAL CONTROL OF BREATHING. American Journal of Physiology 130(1):155-170.
• Hall, W. H., Barila, T. G., Metzger, E. C. and Gupta, K. K. (1965). A Clinical Study of Acute Mountain Sickness. Archives of Environmental Health 10(1):747-753.
• Hasselgren, P. O., Alamdari, N., Aversa., Gonnella, P., Smith, I. J. and Tizio, S. (2010). Corticosteroids and muscle wasting: role of transcription factors, nuclear cofactors, and hyperacetylation. Current Opinion in Clinical Nutrition and Metabolic Care 13(4):423-428.
• Havryliuk, T., Acharya, B., Caruso, E. and Cushing, T. (2015). Understanding of Altitude Illness and Use of Pharmacotherapy Among Trekkers and Porters in the Annapurna Region of Nepal. High Altitude Medicine & Biology 16(3):236-243.
• Hue, C. D., Cho, F. S., Cao, S., Dale Bass, C. R., Meaney, D. F. and Morrison, B., 3rd. (2015). Dexamethasone Potentiates in Vitro Blood-Brain Barrier Recovery after Primary Blast Injury by Glucocorticoid Receptor-Mediated Upregulation of ZO-1 Tight Junction Protein. Journal of Cerebral Blood Flow & Metabolism 35(7):1191-1198.
• Hyongbum, K., Lee, J. M., Park, J. S., Jo, S. A., Kim, Y. O., Kim, C. W. and Jo, I. (2008). Dexamethasone coordinately regulates angiopoietin-1 and VEGF: a mechanism of glucocorticoid-induced stabilization of blood-brain barrier. Biochemical and Biophysical Research Communications 372(1):243-248.
• Jones, R., 3rd. and Rhee, D. J. (2006). Corticosteroid-induced ocular hypertension and glaucoma: a brief review and update of the literature. Current Opinion in Ophthalmology 17(2):163-167.
• Kamber, M. (2011). Development of the role of National Anti-Doping Organisations in the fight against doping: From past to future. Forensic Science International 213(1-3):3-9.
• Kelly, T. E. and Hackett, P. H. (2010). Acetazolamide and Sulfonamide Allergy: A Not So Simple Story. High Altitude Medicine and Biology 11(4):319-323.
• Klein, G. L. (2015). The effect of glucocorticoids on bone and muscle. Osteoporosis and Sarcopenia 1(1):39-45.
• Küpper, T., Schöffl, V. and Netzer, N. (2008). Cheyne stokes breathing at high altitude: a helpful response or a troublemaker? International Journal of the Science and Practice of Sleep Medicine 12(2):123-127.
• Landry, G. L. and Kokotailo, P. K. (1994). Drug screening in the athletic setting. Current Problems in Pediatrics 24(10):344-359.
• Leaf, D. E. and Goldfarb, D. S. (2007). Mechanisms of action of acetazolamide in the prophylaxis and treatment of acute mountain sickness. Journal of Applied Physiology 102(4):1313-1322.
• Lee, S. H. (2015). Intestinal Permeability Regulation by Tight Junction: Implication on Inflammatory Bowel Diseases Intestinal Research 13(1):11-18.
• Li, X. and Zhang, P. (2018). Advances in Anti-Doping Analytical Approaches: Challenges and Solutions. Current Pharmaceutical Analysis 14(3):167-174.
• Lipman, G. S., Pomeranz, D., Burns, P., Phillips, C., Cheffers, M., Evans, K., … Hackett, P. (2018). Budesonide Versus Acetazolamide for Prevention of Acute Mountain Sickness. The American Journal of Medicine 131(2):200.e9-200.e16.
• Luks, A. M., Grissom, C., Freer, L. and Hackett, P. (2016). Medication Use Among Mount Everest Climbers: Practice and Attitudes. High Altitude Medicine & Biology 17(4):315-322.
• Luks, A. M., McIntosh, S. E., Grissom, C. K., Auerbach, P. S., Rodway, G. W., Schoene, R. B., … Hackett, P. H. (2014). Wilderness Medical Society Practice Guidelines for the Prevention and Treatment of Acute Altitude Illness: 2014 Update. Wilderness & Environmental Medicine 25(4):S4-S14.
• Maisey, D. N. and Brown, R. D. (1981). Acetazolamide and symptomatic metabolic acidosis in mild renal failure. British Medical Journal 283(6305):1527-1528.
• Marussi, R. V. H., Pedroso, L. J., Piccolo, M. A., Barsottini, G. O., Moraes, D. F. M., Oliveira, B. A. S., … Amaral, D. L. L. F. (2017). Teaching NeuroImages: Typical neuroimaging features in high-altitude cerebral edema. Neurology 89(14):e176-e177.
• Medhi, G., Lachungpa, T. and Saini, J. (2018). Neuroimaging features of fatal high-altitude cerebral edema. Indian Journal of Radiology and Imaging 28(4):401-405.
• Miell, J. P., Englaro, P. and Blum, W. F. (1996). Dexamethasone induces an acute and sustained rise in circulating leptin levels in normal human subjects. Hormone and Metabolic Research 26(12):704-707.
• Owen, E. E., Tyor, M. P., Flanagan, J. F. and Berry, J. N. (1960). THE KIDNEY AS A SOURCE OF BLOOD AMMONIA IN PATIENTS WITH LIVER DISEASE: THE EFFECT OF ACETAZOLAMIDE. The Journal of Clinical Investigation 39(2):288-294.
• Paisley, K. E. and Tomson, C. R. V. (1999). Calcium phosphate stones during long-term acetazolamide treatment for epilepsy. Postgraduate Medical Journal 75(885):427-428.
• Perez, A., Jansen-Chaparro, S., Saigi, I., Bernal-Lopez, M. R., Miñambres, I. and Gomez-Huelgas, R. (2014). Glucocorticoid-induced hyperglycemia. Journal of Diabetes 6(1):9-20.
• Petrovic, S. and Dubose, T. D. (2013). Missense mutations and proximal RTA. Have we reached a new threshold? Focus on “missense mutation T485S alters NBCe1-A electrogenicity causing proximal renal tubular acidosis”. American Journal of Physiology. Cell Physiology 305(4):C373-C374.
• Reardon, C. L. and Creado, S. (2014). Drug abuse in athletes. Substance Abuse and Rehabilitation 5(1):95-105.
• Sagoo, R. S., Hutchinson, C. E., Wright, A., Handford, C., Parsons, H., Sherwood, V., … Imray, C. H. (2017). Magnetic Resonance investigation into the mechanisms involved in the development of high-altitude cerebral edema. Journal of Cerebral Blood Flow & Metabolism 37(1):319-331.
• Spaeth, G. L. (1967). Potassium, acetazolamide, and intraocular pressure. Archives of Ophthalmology 78(5):578-582.
• Swenson, E. R. (1984). The Respiratory Aspects of Carbonic Anhydrase. Annals New York Academy of Sciences 429(1):547-560.
• Thou-Zuchman, O., Shohami, E., Alexandrovich, A. G. and Leker, R. R. (2010). Vascular endothelial growth factor increases neurogenesis after traumatic brain injury. Journal of Cerebral Blood Flow & Metabolism 30(5):1008-1016.
• Tsuruoka, S., Swenson, E. R., Petrovic, S., Fujimura, A. and Schwartz, G. J. (2001). Role of basolateral carbonic anhydrase in proximal tubular fluid and bicarbonate absorption. American Journal of Physiology. Renal Physiology 280(1):F146-F154.
• Vardy, J., Chiew, K. S., Galica, J., Pond, G. R. and Tannock, I. F. (2006). Side effects associated with the use of dexamethasone for prophylaxis of delayed emesis after moderately emetogenic chemotherapy. British Journal of Cancer 94(7):1011-1015.
• Wagner, D. R. (2012). Medical and Sporting Ethics of High Altitude Mountaineering: The Use of Drugs and Supplemental Oxygen. Wilderness & Environmental Medicine 23(3):205-206.
• Walmsley, R. N. and White, G. H. (1985). Normal “Anion Gap” (Hyperchloremic) Acidosis. Clinical Chemistry 31(2):309-313.
• Wang, X., Chen, H., Li, R., Fu, W. and Yao, C. (2018). The effects of respiratory inhaled drugs on the prevention of acute mountain sickness. Medicine 97(32):e11788.
• Zafren, K. (2014). Prevention of high altitude illness. Travel Medicine and Infectious Disease 12(1):29-39.