Combined treatment with acetazolamide and medroxyprogesterone in chronic obstructive pulmonary disease patients

Abstract

Combined treatment with acetazolamide and medroxyprogesterone in chronic obstructive pulmonary disease patients. M. Wagenaar, P. Je Vos, Y.F. Heijdra, L.J. Teppema, H.T.M. Folgering. #ERS Journals Ltd 2002. ABSTRACT: Medroxyprogesterone acetate (MPA) and acetazolamide (ACET) are two ventilatory stimulants which are used in hypoxic and hypercapnic patients with chronic obstructive pulmonary disease (COPD).In a double-blind randomised study, the effects of a 2-week treatment with MPA (30 mg b.i.d.) or ACET (250 mg b.i.d.), followed by a 2-week treatment with a combination of both drugs (MPA/ACET), on daytime and nocturnal ventilatory and blood gas parameters in 17 stable hypercapnic COPD patients were investigated.ACET, MPA and MPA/ACET treatment decreased mean daytime carbon dioxide tension in arterial blood by 0.4, 0.7 and 1.2 kPa, respectively. Minute ventilation was improved only with combined therapy, from 9.3 to 11.2 L?min -1 . With MPA/ACET therapy, the hypercapnic and hypoxic ventilatory responses significantly increased, from 3.7 to 5.8 L?min -1 ?kPa -1 and from -0.13 to -0.40 L?min -1 ?% -1 , respectively. The mouth exclusion pressure response to hypoxia increased during combination therapy, from -0.01 to -0.03 kPa?% -1 . Nocturnal end-tidal carbon dioxide tension decreased with MPA and MPA/ACET treatment, by 0.9 and 1.4 kPa, respectively. MPA/ACET significantly increased mean nocturnal arterial oxygen saturation values, from 85.5 to 90.2%.The authors conclude that short-term combined treatment with medroxyprogesterone acetate and acetazolamide has a more favourable effect on day and night-time blood gas values and chemical drive than single drug treatment.

Medroxyprogesterone improves nocturnal breathing in postmenopausal women with chronic obstructive pulmonary disease

“…In the present study, lowering of tcCO 2 was short-lived paralleling to the pattern observed in base excess previously in awake patients[10]. Our findings are consistent with those observed in 17 hypercapnic stable patients with COPD, where nocturnal end-tidal CO 2 decreased by 0.9 kPa with MPA (60 mg/d/2 weeks)[9]. Our results are also in line with observations in awake healthy males, where MPA increased alveolar ventilation and slopes of hypercapnic and hypoxic ventilatory responses[23].…”

“…The respiratory effects of a two-week treatment with MPA of 60 mg daily subsided within 14 days in healthy male subjects[29]. In patients with COPD, Wagenaar and coworkers did not observe any after-effects on respiration one month after cessation of combined therapy with MPA and acetazolamide (gender distribution in study population not reported)[9]. Prolonged improvement of daytime PaCO 2 in women with chronic respiratory insufficiency[10] and of nocturnal end tidal CO 2 in postmenopausal women with partial upper airway obstruction during sleep[13] has been a consistent finding in our previous studies.…”

“…Many studies have investigated effects of progestins on breathing in awake subjects but few studies have evaluated the effect of progestin treatment on nocturnal breathing in patients with respiratory insufficiency, mostly due to COPD [4-9]. In light of the previous observations, the effect of progestin therapy on breathing may be weaker during sleep[5].…”

Progesterone: the forgotten hormone in men?

“…Also, the combination of the carbonic anhydrase inhibitor acetazolamide with either CMA or MPA seems to be effective for the treatment of COPD 161,162 .…”

Carbonic Anhydrase as a Model for Biophysical and Physical-Organic Studies of Proteins and Protein−Ligand Binding

“…Inhibition of CA V can reduce gluconeogenesis, 113,114 ureagenesis, and lipogenesis. 115,116 Inhibitors of CA are used to treat acute mountain sickness, 117,118 to improve the arterial oxygenation of patients suffering from chronic obstructive pulmonary disease (COPD), 119,120 and as antimicrobial agents. 121 Supuran, Chegwidden, and others have recently observed that inhibitors of carbonic anhydrase inhibit the growth of several types of tumors in cell culture and in vivo.…”