Comparison of acetazolamide and medroxyprogesterone as respiratory stimulants in hypercapnic patients with COPD. Effects of chlormadinone acetate, acetazolamide and oxygen on awake and asleep gas exchange in patients with chronic obstructive pulmonary disease (COPD). Efficacy and tolerability of acetazolamide in migraine prophylaxis: a randomised placebo-controlled trial. Evaluation of vasomotor reactivity by transcranial Doppler and acetazolamide test before and after extracranial-intracranial bypass in patients with internal carotid artery occlusion. Haemodynamic changes in peripheral arterial circulation during antihypertensive treatment with captopril, methyldopa and indapamide. Effect of continuous administration of conjugated estrogen plus medroxyprogesterone acetate (Premelle) in postmenopausal women in Taiwan. Flow-mediated dilation in patients with coronary artery disease is enhanced by high dose atorvastatin compared to combined low dose atorvastatin and ezetimibe: results of the CEZAR study. Dopamine agonist cabergoline reduces hemoconcentration and ascites in hyperstimulated women undergoing assisted reproduction. Role of protriptyline and acetazolamide in the sleep apnea/hypopnea syndrome.
Acetazolamide and medroxyprogesterone acetate (MPA) are two respiratory stimulants that can be used in patients with stable hypercapnic COPD.
                The effects of acetazolamide, 250 mg bid, and MPA, 30 mg bid, on daytime and nighttime blood gas values and the influences on the hypercapnic and hypoxic ventilatory and mouth occlusion pressure (P(0.1)) at 100 ms response were studied in a crossover design in 12 hypercapnic patients with stable COPD (FEV(1), 33 +/- 4% predicted [mean +/- SEM]).
                Daytime PaCO(2) decreased from 47.3 +/- 0.8 mm Hg (placebo) to 42.0 +/- 1.5 mm Hg during acetazolamide treatment (p < 0.05) and to 42.8 +/- 1.5 mm Hg during MPA treatment (p < 0.05). Daytime PaO(2) improved with acetazolamide from 65.2 +/- 2.3 to 75.0 +/- 3.0 mm Hg (p < 0.05), whereas no significant changes were seen with MPA. Mean nocturnal end-tidal carbon dioxide tension decreased with both treatments, from 42.0 +/- 2.3 to 35.3 +/- 2.3 mm Hg with acetazolamide (p < 0.05) and to 34.5 +/- 0.8 mm Hg with MPA (p < 0.05). The percentage of time that the nocturnal arterial oxygen saturation was < 90% was reduced significantly with acetazolamide, from 34.9 +/- 10.7% to 16.3 +/- 7.5% (p < 0.05). Mean nocturnal saturation did not change with MPA. Resting minute ventilation increased significantly only with MPA from 9.6 +/- 0.7 to 10.8 +/- 0.8 L/min (p < 0.05). The slope of the hypercapnic ventilatory response did not change during acetazolamide and MPA therapy. The hypoxic ventilatory response increased from - 0.2 +/- 0.05 to - 0.4 +/- 0.1 L/min/% during acetazolamide (p < 0.05) and to - 0.3 +/- 0.1 L/min/% during MPA (p < 0.05). The hypoxic P(0.1) response improved with acetazolamide treatment from - 0.05 +/- 0.008 to - 0.15 +/- 0.02 mm Hg/% (p < 0.05).
                This study shows that acetazolamide and MPA both have favorable effects on daytime and nighttime blood gas parameters in ventilatory-limited patients with stable COPD. However, the use of acetazolamide is preferred because of its extra effect on nocturnal saturation. The purpose of this study was to assess the short-term effects of chlormadinone acetate (CMA), a synthetic progestogen, acetazolamide (ACET) and oxygen on awake and asleep blood gas values. The study was conducted according to a randomized, double-blind and placebo-controlled design in 53 hypoxaemic patients with chronic obstructive pulmonary disease. On the first two consecutive nights, all patients received either room air or oxygen, via a nasal cannula, in random order. They then received either CMA (25 mg), ACET (250 mg) or placebo twice a day, all in identical capsules. On the third study night, after one week of drug treatment, the patients were tested breathing room air. CMA and ACET therapy decreased mean daytime arterial carbon dioxide tension (PaCO2) by 0.7 and 0.5 kPa, respectively, and night-time end-tidal carbon dioxide tension (PETCO2) by 0.5 and 0.3 kPa, respectively. Supplemental oxygen caused increased CO2 retention during the day and night (0.6 and 0.3 kPa, respectively. Daytime arterial oxygen tension (PaO2) increased to the same extent during ACET (1.9 kPa) and oxygen (2.5 kPa). Asleep oxygen saturation improved most with oxygen supplementation (7%), although ACET also caused significant improvement (4%). CMA administration had virtually no effect on mean awake and asleep hypoxaemia. ACET therapy significantly improved subjective sleep quality. On CMA, minute ventilation increased in association with an augmentation of the hypercapnic ventilatory response. ACET treatment increased both hypercapnic and hypoxic ventilatory responses. We conclude from the group of patients with COPD studied, that the short-term effects of ACET treatment on gas exchange compare favourably with those of CMA. Oxygen therapy improves oxygenation slightly more than ACET, but aggravates CO2 retention. Familial hemiplegic migraine and episodic ataxia type 2 (EA2) are allelic disorders with distinct types of mutations in the CACNA1A gene. EA2 attacks are remarkably sensitive to acetazolamide, a carbonic anhydrase inhibitor. The effectiveness of acetazolamide in migraine prophylaxis is unknown.
                To evaluate the efficacy and the tolerability of acetazolamide in migraine prophylaxis.
                We compared daily oral 500 mg acetazolamide and placebo in patients with migraine in a multicentre, double-blind, randomised trial of 12 weeks duration after a run-in period of 4 weeks without treatment. Frequency of attacks at the last trial period of 4 weeks was the primary efficacy criterion. Secondary efficacy criteria were the frequency of attacks per 4 weeks, the severity and duration of attacks, the number of hours with migraine as well as the number of responders with more than 50% reduction in attack frequency.
                53 patients had been enrolled when the study was prematurely stopped because of a high number of withdrawals (34%), primarily linked to acetazolamide related side effects. Considering the primary and secondary efficacy criteria, among the 53 included patients (27 in the placebo group and 26 in the acetazolamide group), no difference between the 2 study groups could be demonstrated. The most frequent adverse events related to acetazolamide were paresthesias and asthenia.
                In this trial, migraine sufferers poorly tolerated acetazolamide given in an oral dose of 500 mg daily. No obvious prophylactic beneficial effect of acetazolamide appeared on migraine attacks. The aim of this trial was to evaluate the effectiveness of extracranial-intracranial bypass with respect to vasomotor reactivity in patients with internal carotid artery occlusions and absent vasomotor reactivity, comparing them with a control group treated conservatively.
                To test vasomotor reactivity in 104 patients with unilateral occlusion of the internal carotid artery, we measured blood flow velocity in the middle cerebral artery by transcranial Doppler sonography both at rest and after injection of acetazolamide. Among the 39 patients who failed to show increased mean blood flow velocity after the acetazolamide test distal to an occluded internal carotid artery by greater than or equal to 10%, 14 subjects subsequently underwent extracranial-intracranial bypass surgery (group A) and 14 age- and sex-matched subjects in whom no such procedure was done composed the control group (group B). Follow-up examinations were performed 3-6 months postoperatively and in the control group 3-6 months after initial examination.
                Baseline values of the mean blood flow velocity at rest on the affected side were reduced in both groups compared with the contralateral healthy side (group A, 46.0 +/- 15.1 cm/sec; group B, 48.1 +/- 16.7 cm/sec) and revealed only a marginal increase after acetazolamide. The contralateral side showed a normal blood flow velocity at rest and an adequate response to acetazolamide in both groups. On the follow-up examination group A demonstrated a normalized vasodilatory capacity. Blood flow velocity increased significantly after acetazolamide from 41.9 +/- 13.1 cm/sec to 53.5 +/- 16.0 cm/sec (p less than 0.002). In group B, the compromised vasomotor reactivity remained unchanged.
                Our results demonstrate that transcranial Doppler sonography together with the acetazolamide test can identify subjects with reduced vasomotor reactivity distal to an occluded internal carotid artery, who may improve hemodynamically by an extracranial-intracranial bypass. Structural changes in resistance vessels of the lower limbs have been detected in early stages of arterial hypertension. In these patients it might be important to reduce blood pressure by drugs which do not impair peripheral blood flow. Twenty-four patients with arterial hypertension, without target organ damage were randomly given a placebo, 50 mg captopril, 500 mg methyldopa or 2.5 mg indapamide and their blood pressure, arterial blood flow and peripheral resistance were measured at baseline and at the peak action of the antihypertensive treatment. Significant decreases in blood pressure and peripheral resistance have been induced by a single oral dose of captopril and methyldopa: a concomitant significant increase in peripheral blood flow to the lower limbs was also observed during methyldopa treatment. No acute effect was observed on the placebo or on indapamide: the latter induced a decrease in blood pressure and in peripheral resistance along with an increase in arterial blood flow during long-term treatment after four weeks of therapy. Our observations seem to support the usefulness in hypertensive patients with concomitant lesions in the peripheral arterial tree of antihypertensive agents such as methyldopa and indapamide which increase blood flow and reduce peripheral resistance while lowering high blood pressure. To compare the metabolic effects on lipids and acceptability and safety of, and compliance with, a continuous administration of conjugated estrogen plus medroxyprogesterone acetate (Premelle) versus a placebo in non-hysterectomized postmenopausal women.
                Sixty-six generally healthy, female, early post-menopausal women, from 45-60 years of age, were randomized for an administration of conjugated estrogen plus medroxyprogesterone acetate (Premelle, Premarin 0.625 mg plus medroxyprogesterone acetate 2.5 mg/tablet orally) or a placebo for 6 months. The changes in each patient's lipid profiles from baseline, the frequency of hot flushes, bleeding occurrences, and climacteric symptoms, were evaluated. Safety was monitored by means of physical examination, Papanicolau smear, transvaginal ultrasonography, and laboratory check-up. Adverse events were also recorded.
                The difference before and after treatment in serum LDL-C and total cholesterol (TC) was statistically significant in the Premelle group (LDL-C, p = 0.006, TC, p = 0.040). No statistically significant difference in the change from baseline was observed in the levels of LDL-C and TC in the placebo treatment group. There was a statistically significant change from baseline in menopausal symptoms, which were evaluated by the Greene Climacteric Scales in the Premelle group. There was no clinically significant finding in the physical examination, vital signs, laboratory data, or endometrial thickness in either treatment group. The difference in the number of patients who reported an adverse event was not statistically significant between the 2 treatment groups.
                This study demonstrated that Premelle was effective in decreasing LDL-C and total cholesterol levels, and also showed an improvement in some menopausal symptoms, such as vasomotor and sexual dysfunction symptoms. No significant bleeding was observed with Premelle, which was well tolerated in this study. The results of this study could support the use of Premelle tablets as a convenient alternative hormone therapy. Effects independent from cholesterol reduction on vascular function are considered to importantly contribute to the beneficial effects of statin therapy in cardiovascular disease. We aimed to evaluate the effect of high versus low dose atorvastatin on endothelial dysfunction in patients with coronary artery disease (CAD) in a setting of comparable cholesterol reduction.
                Fifty-eight patients with CAD were randomly assigned to double-blind treatment for 8 weeks with atorvastatin 80 mg per day (A80) or atorvastatin 10mg+ezetimibe 10mg per day (A10E10), respectively. Flow-mediated vasodilation (FMD) of the brachial artery, nitroglycerin-mediated endothelium-independent vasodilation (NMD), lipid, C-reactive protein (CRP) plasma concentrations and urinary 8-iso-prostaglandin F2alpha excretion were measured before and after treatment. Total cholesterol, triglycerides and LDL-cholesterol levels were significantly reduced with no difference between A80 and A10E10. A80 caused significantly stronger improvement of FMD compared to A10E10 (absolute change FMD: A80+2.7+/-3.0% (post vs. pre p<0.001), A10E10+0.6+/-2.9% (post vs. pre p=0.25), A80 vs. A10E10 p=0.018). NMD was improved by A80 but not by A10E10 (absolute change NMD: A80+2.7+/-4.6%, A10E10+0.7+/-3.5%, p=0.12). Both treatment groups caused a comparable reduction of CRP and did not effect urinary 8-iso-prostaglandin F2alpha excretion. There was no correlation between FMD or NMD change and LDL-cholesterol change in either treatment group.
                The present findings clearly suggest that in the presence of comparable LDL-lowering effects of both treatment forms, LDL-cholesterol independent effects of high dose atorvastatin therapy account for the improvement of endothelium-dependent vasodilation in patients with stable CAD. Ovarian hyperstimulation syndrome (OHSS) results from increased vascular permeability (VP) caused by ovarian hypersecretion of vascular endothelial growth factor (VEGF), which activates its receptor-2. In animals, the dopamine receptor 2 agonist cabergoline (Cb2) inactivates VEGF receptor-2 and prevents increased VP.
                Our objective was to test whether Cb2 reduces VP and prevents OHSS in humans.
                We conducted a prospective, randomized, double-blind study on oocyte donors at risk of developing OHSS (>20 follicles, >12 mm developed, and >20 oocytes retrieved).
                Cb2 0.5 mg/d (n = 37) or a placebo (n = 32) was administered from the day of human chorionic gonadotropin (d 0) until d 8. Ascites (a pocket of peritoneal fluid > 9 cm(2) in lithotomy position), hemoconcentration, and serum prolactin were recorded. Pharmacokinetic studies with magnetic resonance employing the transfer constant rate (K(trans), measure of permeability) and the extravascular extracellular space (upsilon(e), marker of cellular leakage) were performed to measure VP objectively.
                Hematocrit (P < 0.01), hemoglobin (P = 0.003), and ascites (P = 0.005) were significantly lower on d 4 and 6 after treatment with Cb2 as compared with placebo. The incidence of moderate OHSS was 20.0 and 43.8%, respectively (P = 0.04). Magnetic resonance studies showed an increase in VP and extravascular leakage of fluid 5 d after human chorionic gonadotropin injection that was significantly prevented with Cb2 (K(trans) P = 0.04 and upsilon(e) P = 0.001, respectively).
                Given that Cb2 is a well-established and safe medication, this study provides proof of concept for the use of dopamine agonists in the prevention of OHSS in women undergoing assisted reproduction. The role of drug therapy in the treatment of the sleep apnea/hypopnea syndrome is unclear. In a randomised, double-blind, placebo-controlled study, we investigated the value of 14-day therapy with protriptyline (20 mg daily) or acetazolamide (250 mg 4 times per day) on symptoms and on the frequency of apneas, hypopneas, arousals, and 4% desaturations in 10 patients with obstructive sleep apnea/hypopnea syndrome. Overall, protriptyline did not have a significant effect either on symptoms or on any of the above polysomnographic criteria. Acetazolamide reduced the apnea/hypopnea frequency [placebo 50 +/- 26 (SD); acetazolamide 26 +/- 20/h of sleep, p less than 0.03] and tended to decrease the frequency of 4% desaturations (placebo 29 +/- 20; acetazolamide 19 +/- 16/h of sleep, p = 0.06). Despite these physiological improvements, acetazolamide did not significantly improve symptoms and paraesthesiae were common. Contrary to earlier studies, we conclude that protriptyline may have a limited role in the treatment of the sleep apnea syndrome. The reason why acetazolamide produced a physiological, but not a symptomatic, response requires further investigation.
Acetazolamide can produce a small increase in arterial PO2 and fall in PCO2. These conclusions are drawn from a few small short studies that were not all of high quality. It is not known whether this physiological improvement is associated with clinical benefit.