Abstract
The effects of almitrine bismesylate and medroxyprogesterone acetate on oxygenation during wakefulness and sleep were compared in six patients with chronic obstructive lung disease and carbon dioxide retention. Patients received 1.5 mg/kg almitrine (a peripheral chemoreceptor stimulant), 100 mg of medroxyprogesterone (a central respiratory stimulant), or matched placebo daily for 15 days in random order in a crossover trial. When subjects were awake almitrine increased the ventilatory response to hypoxia and increased arterial oxygen tension (PaO2) to a greater extent than medroxyprogesterone, whereas medroxyprogesterone augmented the ventilatory response to hypercapnia and decreased arterial carbon dioxide tension (PaCO2) to a greater extent than almitrine. Neither drug influenced sleep architecture significantly, except that medroxyprogesterone increased the number of arousals. Almitrine had a more favourable effect than placebo on oxygenation as estimated from arterial oxygen saturation (SaO2) during the different stages of sleep, the number of episodes of hypoxaemia, and the amount of time that SaO2 was below 80%. The only change with medroxyprogesterone by comparison with placebo was a decrease in the number of hypoxaemic episodes. It is concluded that both active drugs improved blood gases during wakefulness, but that 1.5 mg/kg of almitrine is superior to 100 mg of medroxyprogesterone in improving SaO2 during sleep.
Full text
PDF



Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bee D., Gill G. W., Emery C. J., Salmon G. L., Evans T. W., Barer G. R. Action of almitrine on the pulmonary vasculature in ferrets and rats. Bull Eur Physiopathol Respir. 1983 Nov-Dec;19(6):539–545. [PubMed] [Google Scholar]
- Catterall J. R., Calverley P. M., MacNee W., Warren P. M., Shapiro C. M., Douglas N. J., Flenley D. C. Mechanism of transient nocturnal hypoxemia in hypoxic chronic bronchitis and emphysema. J Appl Physiol (1985) 1985 Dec;59(6):1698–1703. doi: 10.1152/jappl.1985.59.6.1698. [DOI] [PubMed] [Google Scholar]
- Catterall J. R., Douglas N. J., Calverley P. M., Shapiro C. M., Flenley D. C. Arterial oxygenation during sleep in patients with right-to-left cardiac or intrapulmonary shunts. Thorax. 1983 May;38(5):344–348. doi: 10.1136/thx.38.5.344. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Connaughton J. J., Douglas N. J., Morgan A. D., Shapiro C. M., Critchley J. A., Pauly N., Flenley D. C. Almitrine improves oxygenation when both awake and asleep in patients with hypoxia and carbon dioxide retention caused by chronic bronchitis and emphysema. Am Rev Respir Dis. 1985 Aug;132(2):206–210. doi: 10.1164/arrd.1985.132.2.206. [DOI] [PubMed] [Google Scholar]
- Cormick W., Olson L. G., Hensley M. J., Saunders N. A. Nocturnal hypoxaemia and quality of sleep in patients with chronic obstructive lung disease. Thorax. 1986 Nov;41(11):846–854. doi: 10.1136/thx.41.11.846. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dolly F. R., Block A. J. Medroxyprogesterone acetate and COPD. Effect on breathing and oxygenation in sleeping and awake patients. Chest. 1983 Oct;84(4):394–398. doi: 10.1378/chest.84.4.394. [DOI] [PubMed] [Google Scholar]
- Fleetham J., West P., Mezon B., Conway W., Roth T., Kryger M. Sleep, arousals, and oxygen desaturation in chronic obstructive pulmonary disease. The effect of oxygen therapy. Am Rev Respir Dis. 1982 Sep;126(3):429–433. doi: 10.1164/arrd.1982.126.3.429. [DOI] [PubMed] [Google Scholar]
- Fletcher E. C., Miller J., Divine G. W., Fletcher J. G., Miller T. Nocturnal oxyhemoglobin desaturation in COPD patients with arterial oxygen tensions above 60 mm Hg. Chest. 1987 Oct;92(4):604–608. doi: 10.1378/chest.92.4.604. [DOI] [PubMed] [Google Scholar]
- Kimura H., Tatsumi K., Kuriyama T., Sugita T., Watanabe S., Nishibayashi Y., Honda Y. Effect of chlormadinone acetate, a synthetic progesterone, on restoring impaired load compensation in chronic obstructive pulmonary disease. Tohoku J Exp Med. 1986 Jun;149(2):119–132. doi: 10.1620/tjem.149.119. [DOI] [PubMed] [Google Scholar]
- Mélot C., Naeije R., Rothschild T., Mertens P., Mols P., Hallemans R. Improvement in ventilation-perfusion matching by almitrine in COPD. Chest. 1983 Mar;83(3):528–533. doi: 10.1378/chest.83.3.528. [DOI] [PubMed] [Google Scholar]
- Powles A. C., Tuxen D. V., Mahood C. B., Pugsley S. O., Campbell E. J. The effect of intravenously administered almitrine, a peripheral chemoreceptor agonist, on patients with chronic air-flow obstruction. Am Rev Respir Dis. 1983 Mar;127(3):284–289. doi: 10.1164/arrd.1983.127.3.284. [DOI] [PubMed] [Google Scholar]
- Read D. J. A clinical method for assessing the ventilatory response to carbon dioxide. Australas Ann Med. 1967 Feb;16(1):20–32. doi: 10.1111/imj.1967.16.1.20. [DOI] [PubMed] [Google Scholar]
- Skatrud J. B., Dempsey J. A., Bhansali P., Irvin C. Determinants of chronic carbon dioxide retention and its correction in humans. J Clin Invest. 1980 Apr;65(4):813–821. doi: 10.1172/JCI109732. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Skatrud J. B., Dempsey J. A., Iber C., Berssenbrugge A. Correction of CO2 retention during sleep in patients with chronic obstructive pulmonary diseases. Am Rev Respir Dis. 1981 Sep;124(3):260–268. doi: 10.1164/arrd.1981.124.3.260. [DOI] [PubMed] [Google Scholar]
- Skatrud J. B., Dempsey J. A. Relative effectiveness of acetazolamide versus medroxyprogesterone acetate in correction of chronic carbon dioxide retention. Am Rev Respir Dis. 1983 Apr;127(4):405–412. doi: 10.1164/arrd.1983.127.4.405. [DOI] [PubMed] [Google Scholar]
- Sorli J., Grassino A., Lorange G., Milic-Emili J. Control of breathing in patients with chronic obstructive lung disease. Clin Sci Mol Med. 1978 Mar;54(3):295–304. doi: 10.1042/cs0540295. [DOI] [PubMed] [Google Scholar]
- Stradling J. R., Barnes P., Pride N. B. The effects of almitrine on the ventilatory response to hypoxia and hypercapnia in normal subjects. Clin Sci (Lond) 1982 Oct;63(4):401–404. doi: 10.1042/cs0630401. [DOI] [PubMed] [Google Scholar]
- Stradling J. R., Lane D. J. Nocturnal hypoxaemia in chronic obstructive pulmonary disease. Clin Sci (Lond) 1983 Feb;64(2):213–222. doi: 10.1042/cs0640213. [DOI] [PubMed] [Google Scholar]
- Stradling J. R., Nicholl C. G., Cover D., Davies E. E., Hughes J. M., Pride N. B. The effects of oral almitrine on pattern of breathing and gas exchange in patients with chronic obstructive pulmonary disease. Clin Sci (Lond) 1984 Apr;66(4):435–442. doi: 10.1042/cs0660435. [DOI] [PubMed] [Google Scholar]
- Voelkel N. F. Mechanisms of hypoxic pulmonary vasoconstriction. Am Rev Respir Dis. 1986 Jun;133(6):1186–1195. doi: 10.1164/arrd.1986.133.6.1186. [DOI] [PubMed] [Google Scholar]
- Zwillich C. W., Natalino M. R., Sutton F. D., Weil J. V. Effects of progesterone on chemosensitivity in normal men. J Lab Clin Med. 1978 Aug;92(2):262–269. [PubMed] [Google Scholar]
