Combined methazolamide and theophylline improves oxygen saturation but not exercise performance or altitude illness in acute hypobaric hypoxia.
acute mountain sickness
carbonic anhydrase
cognitive function
cycling time trial
methylxanthine
Journal
Experimental physiology
ISSN: 1469-445X
Titre abrégé: Exp Physiol
Pays: England
ID NLM: 9002940
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
23
01
2020
accepted:
29
04
2020
pubmed:
5
5
2020
medline:
22
2
2022
entrez:
5
5
2020
Statut:
ppublish
Résumé
What is the central question of this study? Does the combination of methazolamide and theophylline reduce symptoms of acute mountain sickness (AMS) and improve aerobic performance in acute hypobaric hypoxia? What is the main finding and its importance? The oral combination of methazolamide (100 BID) and theophylline (300 BID) improved arterial oxygen saturation but did not reduce symptoms of AMS and impaired aerobic performance. We do not recommend this combination of drugs for prophylaxis against the acute negative effects of hypobaric hypoxia. A limited number of small studies have suggested that methazolamide and theophylline can independently reduce symptoms of acute mountain sickness (AMS) and, if taken together, can improve aerobic exercise performance in normobaric hypoxia. We performed a randomized, double-blind, placebo-controlled, cross-over study to determine if the combination of oral methazolamide and theophylline could provide prophylaxis against AMS and improve aerobic performance in hypobaric hypoxia (∼4875 m). Volunteers with histories of AMS were screened at low altitude (1650 m) and started combined methazolamide (100 mg BID) and theophylline (300 mg BID) treatment, or placebo, 72 h prior to decompression. Baseline AMS (Lake Louise Questionnaire), blood (haemoglobin, haematocrit), cognitive function, ventilatory and pulse oximetry (
Substances chimiques
Theophylline
C137DTR5RG
Methazolamide
W733B0S9SD
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
117-125Informations de copyright
© 2020 The Authors. Experimental Physiology © 2020 The Physiological Society.
Références
Borg, G. A. (1974). Perceived exertion. Exercise and Sport Sciences Reviews, 2(1), 131-153.
Boulet, L. M., Teppema, L. J., Hackett, H. K., Dominelli, P. B., Cheyne, W. S., Dominelli, G. S., … Foster, G. E. (2018). Attenuation of human hypoxic pulmonary vasoconstriction by acetazolamide and methazolamide. Journal of Applied Physiology, 125(6), 1795-1803.
Bradbury, K. E., Yurkevicius, B. R., Mitchell, K. M., Coffman, K. E., Salgado, R. M., Fulco, C. S., … Charkoudian, N. (2020). Acetazolamide does not alter endurance exercise performance at 3500 m altitude. Journal of Applied Physiology, 128(2), 390-396.
Bradwell, A. R., Myers, S. D., Beazley, M., Ashdown, K., Harris, N. G., Bradwell, S. B., … Harris, S. J., & Birmingham Medical Research Expeditionary Society. (2014) Exercise limitation of acetazolamide at altitude (3459 m). Wilderness & Environmental Medicine, 25(3), 272-277.
Dominelli, P. B., McNeil, C. J., Vermeulen, T. D., Stuckless, T. J. R., Brown, C. V., Dominelli, G. S., … Foster, G. E. (2018). Effect of acetazolamide and methazolamide on diaphragm and dorsiflexor fatigue: A randomized controlled trial. Journal of Applied Physiology, 125(3), 770-779.
Fischer, R., Lang, S. M., Leitl, M., Thiere, M., Steiner, U., & Huber, R. M. (2004). Theophylline and acetazolamide reduce sleep-disordered breathing at high altitude. The European Respiratory Journal, 23(1), 47-52.
Fischer, R., Lang, S. M., Steiner, U., Toepfer, M., Hautmann, H., Pongratz, H., & Huber, R. M. (2000). Theophylline improves acute mountain sickness. The European Respiratory Journal, 15(1), 123-127.
Forster, P. (1982). Methazolamide in acute mountain sickness. The Lancet, 319(8283), 1254.
Fulco, C. S., Muza, S. R., Ditzler, D., Lammi, E., Lewis, S. F., & Cymerman, A. (2006). Effect of acetazolamide on leg endurance exercise at sea level and simulated altitude. Clinical Science, 110(6), 683-692.
Garske, L. A., Brown, M. G., & Morrison, S. C. (2003). Acetazolamide reduces exercise capacity and increases leg fatigue under hypoxic conditions. Journal of Applied Physiology, 94(3), 991-996.
Hackett, P. H., & Roach, R. C. (2001). High-altitude illness. The New England Journal of Medicine, 345(2), 107-114.
Jenne, J. W., Wyze, M. S., Rood, F. S., & MacDonald, F. M. (1972). Pharmacokinetics of theophylline. Application to adjustment of the clinical dose of aminophylline. Clinical Pharmacology and Therapeutics, 13(3), 349-360.
Jonk, A. M., van den Berg, I. P., Olfert, I. M., Wray, D. W., Arai, T., Hopkins, S. R., & Wagner, P. D. (2007). Effect of acetazolamide on pulmonary and muscle gas exchange during normoxic and hypoxic exercise. The Journal of Physiology, 579(3), 909-921.
Küpper, T. E. A. H., Strohl, K. P., Hoefer, M., Gieseler, U., Netzer, C. M., & Netzer, N. C. (2008). Low-dose theophylline reduces symptoms of acute mountain sickness. Journal of Travel Medicine, 15(5), 307-314.
Lathan, C., Spira, J. L., Bleiberg, J., Vice, J., & Tsao, J. W. (2013). Defense Automated Neurobehavioral Assessment (DANA)-psychometric properties of a new field-deployable neurocognitive assessment tool. Military Medicine, 178(4), 365-371.
Leaf, D. E., & 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.
Lisk, C., McCord, J., Bose, S., Sullivan, T., Loomis, Z., Nozik-Grayck, E., … Irwin, D. C. (2013). Nrf2 activation: A potential strategy for the prevention of acute mountain sickness. Free Radical Biology & Medicine, 63, 264-273.
Luks, A. M., Auerbach, P. S., Freer, L., Grissom, C. K., Keyes, L. E., McIntosh, S. E., … Hackett, P. H. (2019). Wilderness Medical Society clinical practice guidelines for the prevention and treatment of acute altitude illness: 2019 update. Wilderness & Environmental Medicine, 30(4S), S3-S18.
Luks, A. M., & Swenson, E. R. (2008). Medication and dosage considerations in the prophylaxis and treatment of high-altitude illness. Chest, 133(3), 744-755.
Marcus, M. L., Skelton, C. L., Grauer, L. E., & Epstein, S. E. (1972). Effects of theophylline on myocardial mechanics. The American Journal of Physiology, 222(6), 1361-1365.
Maren, T. H. (1967). Carbonic anhydrase: Chemistry, physiology, and inhibition. Physiological Reviews, 47(4), 595-781.
Maren, T. H., Haywood, J. R., Chapman, S. K., & Zimmerman, T. J. (1977). The pharmacology of methazolamide in relation to the treatment of glaucoma. Investigative Ophthalmology & Visual Science, 16(8), 730-742.
Posch, A. M., Dandorf, S., & Hile, D. C. (2018). The effects of acetazolamide on exercise performance at sea level and in hypoxic environments: a review. Wilderness & Environmental Medicine, 29(4), 541-545.
Radiloff, D. R., Zhao, Y., Boico, A., Wu, C., Shan, S., Palmer, G., … Schroeder, T. (2012). The combination of theophylline and endothelin receptor antagonism improves exercise performance of rats under simulated high altitude. Journal of Applied Physiology, 113(8), 1243-1252.
Roach, E. B., Bleiberg, J., Lathan, C. E., Wolpert, L., Tsao, J. W., & Roach, R. C. (2014). AltitudeOmics: Decreased reaction time after high altitude cognitive testing is a sensitive metric of hypoxic impairment. Neuroreport, 25(11), 814-818.
Roach, R. C., Hackett, P. H., Oelz, O., Bärtsch, P., Luks, A. M., MacInnis, M. J., & Baillie, J. K. & Lake Louise AMS Score Consensus Committee. (2018) The 2018 Lake Louise acute mountain sickness score. High Altitude Medicine & Biology, 19(1), 4-6.
Scalzo, R. L., Binns, S. E., Klochak, A. L., Giordano, G. R., Paris, H. L. R., Sevits, K. J., … Bell, C. (2015). Methazolamide plus aminophylline abrogates hypoxia-mediated endurance exercise impairment. High Altitude Medicine & Biology, 16(4), 331-342.
Schoene, R. B., Bates, P. W., Larson, E. B., & Pierson, D. J. (1983). Effect of acetazolamide on normoxic and hypoxic exercise in humans at sea level. Journal of Applied Physiology: Respiratory, Environmental and Exercise Physiology, 55(6), 1772-1776.
Stager, J. M., Tucker, A., Cordain, L., Engebretsen, B. J., Brechue, W. F., & Matulich, C. C. (1990). Normoxic and acute hypoxic exercise tolerance in man following acetazolamide. Medicine and Science in Sports and Exercise, 22(2), 178-184.
Starr, I., Gamble, C. J., Margolies, A., Donal, J. S., Joseph, N., & Eagle, E. (1937). A clinical study of the action of 10 commonly used drugs on cardiac output, work and size; on respiration, on metabolic rate and on the electrocardiogram. The Journal of Clinical Investigation, 16(5), 799-823.
Stepanek, J., Cocco, D., Pradhan, G. N., Smith, B. E., Bartlett, J., Studer, M., … Cevette, M. J. (2013). Early detection of hypoxia-lnduced cognitive impairment using the King-Devick test. Aviation, Space, and Environmental Medicine, 84(10), 1017-1022.
Subudhi, A. W., Bourdillon, N., Bucher, J., Davis, C., Elliott, J. E., Eutermoster, M., … Roach, R. C. (2014). AltitudeOmics: The integrative physiology of human acclimatization to hypobaric hypoxia and its retention upon reascent. PLoS One, 9(3), e92191.
Subudhi, A. W., Dimmen, A. C., Julian, C. G., Wilson, M. J., Panerai, R. B., & Roach, R. C. (2011). Effects of acetazolamide and dexamethasone on cerebral hemodynamics in hypoxia. Journal of Applied Physiology, 110(5), 1219-1225.
Swenson, E. R. (2016). Pharmacology of acute mountain sickness: Old drugs and newer thinking. Journal of Applied Physiology, 120(2), 204-215.
Teppema, L. J., Boulet, L. M., Hackett, H. K., Dominelli, P. B., Cheyne, W. S., Dominelli, G. S., … Foster, G. E. (2020). Influence of methazolamide on the human control of breathing: A comparison to acetazolamide. Experimental Physiology, 105(2), 293-301.
Thorne, D. R. (2006). Throughput: A simple performance index with desirable characteristics. Behavior Research Methods, 38(4), 569-573.
Wright, A. D., Bradwell, A. R., & Fletcher, R. F. (1983). Methazolamide and acetazolamide in acute mountain sickness. Aviation, Space, and Environmental Medicine, 54(7), 619-621.