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PubMed1994

Acetazolamide reactivity on 123I-IMP single photon emission computed tomography in patients with major cerebral artery occlusive disease: correlation with positron emission tomography parameters.

Single photon emission computed tomography (SPECT) with acetazolamide challenge has increasingly been used for evaluating hemodynamic reserve in stroke patients. The accuracy of this test, however, has not been validated with positron emission tomography (PET). In 14 patients who had occlusive disease of the internal carotid artery or the trunk of the middle cerebral artery (MCA) with minimal or no infarction on computed tomography (CT) and magnetic resonance imaging (MRI), we compared acetazolamide reactivity on SPECT with N-isopropyl-p-[123I]-iodoamphetamine to hemodynamic parameters determined with gas inhalation labeled 15O steady-state PET studies. The asymmetry index (AI)--i.e., the percentage of the activity rate of the ischemic MCA territory versus the contralateral one, was determined by SPECT. Acetazolamide reactivity expressed as delta AI, or change in AI after acetazolamide challenge, was significantly lower in seven patients than -8.4%, the lower limit of the 95% confidence interval for the normal reactivity. Values of ipsilateral CBF, cerebral blood volume (CBV)/CBF, and oxygen extraction fraction (OEF) and contralateral OEF were significantly different between patients with normal and reduced acetazolamide reactivity. Values of delta AI were correlated with OEF (r = -0.87; p < 0.001) and CBV/CBF (r = -0.56; p < 0.05). All patients with OEF > 0.52, the mean + 2 SD calculated from five normal volunteers, also had reduced acetazolamide reactivity, while the patients with normal OEF values had normal reactivity. The present study has demonstrated that SPECT studies with an acetazolamide challenge can detect the Stage II hemodynamic failure.

Acetazolamide↗
PubMed1989

Effects of acute administration of acetazolamide and frusemide on lithium clearance in humans.

To investigate the mechanism(s) of acute frusemide-induced increases in FELi, the effects of frusemide and acetazolamide, the carbonic anhydrase inhibiting agent, were evaluated in 19 healthy subjects either before or after pretreatment with acetazolamide or frusemide (11 subjects and eight subjects respectively). Acetazolamide pretreatment did not modify frusemide-induced increases in FELi (delta FLi 12.8 +/- 4.1% compared to 14.6 +/- 7.3%, P = NS); similarly, frusemide pretreatment did not modify acetazolamide-induced increases in FELi (delta FLi: 11.3 +/- 5.9% compared to 9.8 +/- 3.8%, P = NS). Acetazolamide-induced changes of FELi were correlated significantly with acetazolamide-induced increases of FEHCO3 (r = 0.61, P less than 0.05), FENa (r = 0.46, P less than 0.05) but not of FECl (r = 0.25, P = NS). On the other hand, frusemide-induced changes of FELi were correlated significantly with frusemide-induced increases of FENa (r = 0.62, P less than 0.005), FEC1 (r = 0.52, P less than 0.025) but not of FEHCO3 (r = 0.3, P = NS). Thus, frusemide effects on tubular lithium reabsorption are not related to carbonic anhydrase inhibition; furthermore, it appears that frusemide and acetazolamide affect lithium reabsorption by different and independent mechanism(s), possibly acting at different nephron site(s).

Acetazolamide↗
PubMed1999

Single versus multiple doses of acetazolamide for metabolic alkalosis in critically ill medical patients: a randomized, double-blind trial.

OBJECTIVE: To compare two dosing regimens of acetazolamide for the reversal of metabolic alkalosis in mechanically ventilated patients with asthma or chronic obstructive pulmonary disease. DESIGN: A randomized, double-blind, placebo-controlled trial. SETTING: A 35-bed medical intensive care unit in a tertiary care teaching hospital. PATIENTS: Forty mechanically ventilated patients with a metabolic alkalosis (arterial pH > or = 7.48 and serum bicarbonate concentration > or = 26 mEq/L) resistant to fluid or potassium therapy (serum potassium concentration, > or = 4 mEq/L) not receiving acetazolamide or sodium bicarbonate in the previous 72 hrs. INTERVENTIONS: Stratified by previous diuretic use and randomized to receive intravenous administration of acetazolamide, one dose of 500 mg or 250 mg every 6 hrs for a total of four doses. MEASUREMENTS AND MAIN RESULTS: Serum bicarbonate and potassium concentrations were drawn every 6 hrs for 72 hrs, arterial blood gases were drawn every 12 hrs for 72 hrs, and both urine chloride and pH were drawn at hours 0, 6, 12, 18, 24, 48, and 72. By using generalized estimating equation techniques, no difference was found between the two dosing regimens at any point over the study period for serum bicarbonate, serum potassium, or urine chloride end points. Results did not differ between diuretic- and nondiuretic-treated patients. Serum bicarbonate concentrations remained significantly decreased in both treatment groups 72 hrs after administration of the first acetazolamide dose (31.8 +/- 4.9-25.3 +/- 3.8 mEq/L, p < .0001 [250 mg x 4]; 31.9 +/- 25.4-25.4 +/- 3.6 mEq/L, p < .0001 [500 mg x 1]). CONCLUSIONS: We conclude that a single 500-mg dose of acetazolamide reverses nonchloride responsive metabolic alkaloses in medical intensive care unit patients as effectively as multiple doses of 250 mg. Studies to examine the prolonged duration of action of acetazolamide observed in this study as well as the effect of acetazolamide on clinical end points, such as duration of mechanical ventilation, are warranted.

Acetazolamide↗
PubMed2001

Effects of acetazolamide on cerebral blood flow, blood volume, and oxygen metabolism: a positron emission tomography study with healthy volunteers.

To evaluate changes in cerebral hemodynamics and metabolism induced by acetazolamide in healthy subjects, positron emission tomography studies for measurement of cerebral perfusion and oxygen consumption were performed. Sixteen healthy volunteers underwent positron emission tomography studies with 15O-gas and water before and after intravenous administration of acetazolamide. Dynamic positron emission tomography data were acquired after bolus injection of H2[15O] and bolus inhalation of 15O2. Cerebral blood flow, metabolic rate of oxygen, and arterial-to-capillary blood volume images were calculated using the three-weighted integral method. The images of cerebral blood volume were calculated using the bolus inhalation technique of C[15O]. The scans for cerebral blood flow and volume and metabolic rate of oxygen after acetazolamide challenge were performed at 10, 20, and 30 minutes after drug injection. The parametric images obtained under the two conditions at baseline and after acetazolamide administration were compared. The global and regional values for cerebral blood flow and volume and arterial-to-capillary blood volume increased significantly after acetazolamide administration compared with the baseline condition, whereas no difference in metabolic rate of oxygen was observed. Acetazolamide-induced increases in both blood flow and volume in the normal brain occurred as a vasodilatory reaction of functioning vessels. The increase in arterial-to-capillary blood volume made the major contribution to the cerebral blood volume increase, indicating that the raise in cerebral blood flow during the acetazolamide challenge is closely related to arterial-to-capillary vasomotor responsiveness.

Acetazolamide↗
PubMed1999

Upregulation of the hyperpolarization-activated cation current in rat thalamic relay neurones by acetazolamide.

1. The effect of inhibition of brain carbonic anhydrase (CA) on the hyperpolarization-activated cation current (Ih) of thalamocortical (TC) neurones of the rat ventrobasal thalamic complex (VB) was investigated in an in vitro slice preparation using the whole-cell patch-clamp technique and fluorescence ratio imaging of the pH indicator 2',7'-bis(carboxyethyl)-5(and -6)-carboxyfluorescein (BCECF). 2. Recording of Ih before and after addition of 0.4-0.8 mM acetazolamide to the bathing fluid revealed a significant shift in the voltage dependence of activation (V ) of 5-7 mV to more positive potentials. 3. Simultaneous recording of Ih and BCECF fluorescence ratio (F420/F495) revealed an increase in Ih amplitude accompanied by an intracellular alkalinization upon application of acetazolamide. The CA inhibitor ethoxyzolamide (EZA, 50 microM) also led to an intracellular alkalinization and a subsequent 4-5 mV positive shift of V of Ih. 4. Acetazolamide and EZA both profoundly slowed the rapid fall of pHi upon switching from Hepes- to CO2/HCO3--buffered superfusate, indicating intracellular CA isoforms in TC neurones. 5. In slices bathed in Hepes-buffered saline, addition of acetazolamide had no effect on the amplitude and time course of activation of Ih, indicating that the action of acetazolamide on Ih was dependent on the presence of HCO3-. 6. Under current-clamp conditions, the neuronal response to hyperpolarizing current pulses in the presence of acetazolamide was decreased as compared to control. This resulted in a strongly reduced ability of TC neurones to produce rebound Ca2+-mediated spikes. 7. The present results implied that in TC neurones acetazolamide led to an intracellular alkalinization which causes, due to its pH sensitivity, an increase in Ih.

Acetazolamide↗
PubMed1998

Hand gripping and acetazolamide effect in normal persons and patients with carotid artery disease.

Transcranial Doppler measurement (TCD) of cerebrovascular reserve (CVR) is usually performed by the CO2 test, the acetazolamide test, or the breath-holding test. Since these tests are time-consuming and labor-intensive, alternative methods such as the hand-gripping test are of interest. Twenty-one normal persons and 25 patients with unilateral carotid artery disease were studied. Flow velocity changes in both middle cerebral arteries (MCAs) during bilateral hand gripping were measured by TCD and compared with acetazolamide test results. The increase in MCA mean flow velocity (FVmean) during hand gripping was 18.0 +/- 6.3% in normal persons; the increases in the post-stenotic MCA were 15.8 +/- 9.7% in all patients and 9.4 +/- 5.4% in patients with impaired CVR as determined by the acetazolamide test. Only in the group with impaired acetazolamide reactivity was the increase in the poststenotic MCA significantly lower compared to that in controls (p < 0.01) and to the contralateral, nonstenotic side (p < 0.01). Nevertheless the FVmean increases in both tests showed a weak, but significant correlation (r = 0.59, p < 0.01). All FVmean increases during hand gripping were significantly (p < 0.01) lower than those during the acetazolamide test. The test appears as a weaker stimulus for MCA blood flow velocity increase than the acetazolamide test. Thus, only a substantial reduction of acetazolamide reactivity leads to a reduced MCA FVmean increase using hand gripping. Although it is highly specific but less sensitive, hand gripping does not appear to be suitable as a screening measure of CVR, but might be useful in addition to standard tests.

Acetazolamide↗
PubMed2026

Acetazolamide to prevent ventilatory drive withdrawal in REM sleep apnoea: a randomised controlled trial.

BACKGROUND: Obstructive sleep apnoea (OSA) pathogenesis during rapid-eye movement (REM) sleep has been linked to dips in ventilatory drive and downstream genioglossus hypotonia. The carbonic anhydrase inhibitor acetazolamide is known to increase ventilatory drive and improve OSA severity. Therefore, we tested the effect of acetazolamide on REM-predominant OSA severity (apnoea hypopnoea index (AHI) and hypoxic burden, co-primary outcomes) and underlying physiological mechanisms (ventilatory drive, ventilation and pharyngeal muscle activity). METHODS: 11 participants with REM-predominant OSA per baseline polysomnography (REM AHI/non-REM AHI&#x2265;2) were allocated to receiving acetazolamide 500&#x2009;mg for three nights (first night at half dose) or placebo according to a randomised, crossover, double-blind design. Detailed physiological polysomnography with recording of diaphragm and genioglossus electromyography was conducted after each intervention, with a 1-week washout in between. RESULTS: As hypothesised, acetazolamide reduced AHI by 35.5% (95% CI 23.1% to 46.3%) and hypoxic burden by 35.9% (95% CI 21.1% to 48.4%) vs placebo (p<0.001), meeting the primary endpoint. Mechanistic analysis in REM revealed that, unexpectedly, acetazolamide did not mitigate dips in ventilatory drive versus placebo (first decile (+0.1 (-1.0 to 1.3) L/min, p=0.8). Rather, acetazolamide reduced collapsibility (increased ventilation at eupneic drive: +1.4 (1.2 to 1.8) L/min) and raised muscle responsiveness (ventilation vs drive slope: +32 (25 to 41) %ventilation/drive, p<0.001; genioglossus versus drive slope: +0.33 (0.13 to 0.54) %max/(L/min), p=0.001). CONCLUSIONS: Acetazolamide modestly improved REM OSA, with meaningful improvements in upper airway physiology, but failed to mitigate the dips in ventilatory drive responsible for REM OSA. TRIAL REGISTRATION NUMBER: NCT05589792.

Humans↗
PubMed2002

Central CO2 chemoreception in developing bullfrogs: anomalous response to acetazolamide.

Central CO(2) chemoreception and the role of carbonic anhydrase were assessed in brain stems from Rana catesbeiana tadpoles and frogs. Buccal and lung rhythms were recorded from cranial nerve VII and spinal nerve II during normocapnia and hypercapnia before and after treatment with 25 microM acetazolamide. The lung response to acetazolamide mimicked the hypercapnic response in early-stage and midstage metamorphic tadpoles and frogs. In late-stage tadpoles, acetazolamide actually inhibited hypercapnic responses. Acetazolamide and hypercapnia decreased the buccal frequency but had no effect on the buccal duty cycle. Carbonic anhydrase activity was present in the brain stem in every developmental stage. Thus more frequent lung ventilation and concomitantly less frequent buccal ventilation comprised the hypercapnic response, but the response to acetazolamide was not consistent during metamorphosis. Therefore, acetazolamide is not a useful tool for central CO(2) chemoreceptor studies in this species. The reversal of the effect of acetazolamide in late-stage metamorphosis may reflect reorganization of central chemosensory processes during the final transition from aquatic to aerial respiration.

Acetazolamide↗
PubMed1995

Effect of adenosine on cerebral blood flow as evaluated by single-photon emission computed tomography in normal subjects and in patients with occlusive carotid disease. A comparison with acetazolamide.

BACKGROUND AND PURPOSE: Acetazolamide is commonly used with single-photon CT to assess the cerebrovascular reserve in patients with internal carotid artery stenosis or occlusion. In this study we wanted to evaluate the effects of adenosine, a well-known vasodilatatory compound with a short biological half-life, on brain circulation in humans and compare the results with those of acetazolamide. METHODS: Acetazolamide (1 g) and adenosine (140 micrograms/kg per minute) were injected intravenously on different days in 6 normal subjects and 6 patients: 4 with unilateral stenosis, 1 with bilateral stenosis, and 1 with complete occlusion of the internal carotid artery. Changes in regional cerebral blood flow relative to that of the cerebellum (cortico/cerebellar ratios) from resting conditions were evaluated by 99mTc-hexamethylpropyleneamine oxime and single-photon emission CT. RESULTS: The measured blood flow ratios increased significantly in the normal group 20 minutes after acetazolamide injection in several cortical and subcortical regions, as well as at the 4th minute of a 6-minute adenosine infusion. Regional cerebral blood flow ratio values were higher after adenosine than after acetazolamide in both cortical (frontal and parietal) and subcortical (thalamus and basal ganglia) regions. In 4 of the 6 patients the side-to-side asymmetry increased from the basal resting condition after the injection of acetazolamide and even more so after the injection of adenosine. CONCLUSIONS: Adenosine infusion causes vasodilation of cerebral arteries and can be used for the investigation of cerebrovascular perfusion capacity in patients with carotid occlusive disease. One advantage in the use of adenosine over acetazolamide is the possibility of interrupting the test with reversal of clinical symptoms or patient discomfort within a few minutes.

Acetazolamide↗
PubMed1996

Acetazolamide in the treatment of seizures.

OBJECTIVE: To summarize the pharmacology, pharmacokinetics, efficacy, and safety of acetazolamide and to evaluate its therapeutic role in patients with epilepsy. DATA SOURCES: A computerized search of the MEDLINE (OVID) database (1966-1994) was used to identify publications regarding acetazolamide. The MEDLINE search was supplemented by information from textbooks. STUDY SELECTION: Included were English-language review articles, clinical trials, cohort studies, and case reports. Topics investigated included basic pharmacology, therapeutics, toxicology, adverse reactions, dosage, administration, and pharmacokinetics of acetazolamide. DATA SYNTHESIS: Acetazolamide, a carbonic anhydrase inhibitor, has been approved for the treatment of epilepsy since 1953. Acetazolamide is primarily used in combination therapy with other antiepileptic medications in both children and adults although it may be used as monotherapy. Drug concentration monitoring has not been found to be routinely beneficial. Adverse effects include kidney stones, metabolic acidosis, lethargy, appetite suppression, paresthesias, and rare blood dyscrasias. Partial tolerance may develop to the antiepileptic activity. CONCLUSIONS: Acetazolamide is a beneficial adjunctive agent in the pharmacotherapy of epilepsy and should be considered in refractory epilepsy. Although it may be useful in partial, myoclonic, absence, and primary generalized tonic-clonic seizures uncontrolled by other marketed agents, acetazolamide has been inadequately studied by current standards and its use has been limited.

Acetazolamide↗
PubMed2004

Development of a topical niosomal preparation of acetazolamide: preparation and evaluation.

Orally administered acetazolamide has a limited use in glaucoma due to the systemic side effects associated with its use. No topical formulation of acetazolamide is available, mainly because of it having a limited aqueous solubility and poor corneal permeation. To enhance the bioavailability of acetazolamide by the topical route and to improve the corneal permeability of the drug, niosomes of acetazolamide were prepared (employing span 60 and cholesterol) by different methods. Transmission electron microscopy (TEM) of the selected formulation was carried out to study the morphology. Niosomes were also prepared in the presence of dicetyl phosphate and stearylamine to obtain negatively and positively charged vesicles, respectively. It was found that the reverse-phase evaporation method (REV) gave the maximum drug entrapment efficiency (43.75%) as compared with ether injection (39.62%) and film hydration (31.43%) techniques. Drug entrapment efficiency varied with the charge and the percent entrapment efficiency for the REV method was 43.75, 51.23 and 36.26% for neutral, positively charged and negatively charged niosomes, respectively. Corneal permeability studies, however, showed that the percent permeation and the apparent permeability coefficient for the charged niosomes were less than for the neutral ones. A bioadhesive niosomal formulation of acetazolamide was also prepared and compared with the positively charged formulation, considering that both of them would have a prolonged stay in the cul-de-sac because of their expected interactions with mucin. The formulations were also compared based on their intraocular pressure (IOP)-lowering capacity. The positively charged niosomes (REV2), although showing good corneal permeability and pharmacodynamics, were however found to be inappropriate in terms of the corneal cell toxicity. The bioadhesive coated formulation (REV1bio) compared well with REV2 and also showed a much lesser toxicity. Further, the IOP-lowering effect of the developed formulations was compared with that of a marketed formulation of dorzolamide 2%, a topical carbonic anhydrase inhibitor. The developed niosomal formulations of acetazolamide showed a comparable physiological effect (33% reduction of IOP in REV1bio and 37% reduction in dorzolamide) with a duration of up to 6 h (the duration being 3 h for dorzolamide). Results of the study indicate that it is possible to develop a safe (as indicated by corneal toxicity studies) and physiologically active topical niosomal formulation of acetazolamide relative in efficiency to the newer local carbonic anhydrase inhibitor, dorzolamide. The developed formulations can form a cost effective treatment plan, which is especially important in the treatment of glaucoma, a chronic ailment affecting middle-aged to old patients.

Acetazolamide↗
PubMed2004

Pressure autoregulation and positron emission tomography-derived cerebral blood flow acetazolamide reactivity in patients with carotid artery stenosis.

OBJECTIVE: Testing autoregulation is of importance in predicting risk of stroke and managing patients with occlusive carotid arterial disease. The use of small spontaneous changes in arterial blood pressure and transcranial Doppler (TCD) flow velocity can be used to assess autoregulation noninvasively without the need for a cerebrovascular challenge. We have previously described an index (called "Mx") that achieves this. Negative or low positive values (<0.4) indicate intact pressure autoregulation, whereas an Mx greater than 0.4 indicates diminished autoregulation. The objective of this study was to compare acetazolamide reactivity of positron emission tomography (PET)-derived cerebral blood flow (CBF) with Mx in patients with carotid arterial disease. METHODS: In 40 patients with carotid arterial disease, we used bilateral TCD recordings of the middle cerebral artery to derive Mx and compared this with PET-derived CBF measurements of acetazolamide reactivity. RESULTS: Mx correlated inversely with baseline PET CBF (P = 0.042, R = -0.349) but not with postacetazolamide CBF or cerebrovascular reactivity to acetazolamide. This may reflect discordance between pressure autoregulation and acetazolamide reactivity. Mx correlated significantly with degree of internal carotid artery stenosis (P = 0.022, R = 0.38), whereas CBF reactivity to acetazolamide did not correlate with Mx (P = 0.22). After the administration of acetazolamide, slow-wave activity in blood pressure and TCD flow velocity recordings was seen to diminish, rendering the calculation of Mx unreliable after acetazolamide. CONCLUSION: The measurement of Mx offers a noninvasive, safe technique for assessing abnormalities of pressure autoregulation in patients with carotid arterial disease.

Acetazolamide↗
PubMed1983

Effects of acetazolamide on iodide transport, electrolyte distribution and activities of carbonic anhydrase, Na+, K+-ATPase and HCO3- -ATPase in mouse, rat and turtle thyroid glands.

The effects of acute (200 mg/kg) and chronic (20 mg/kg per day for 7 days) administration of acetazolamide on iodide transport, electrolyte distribution, and on carbonic anhydrase (CA), Na+, K+-ATPase and HCO3- -ATPase activities were evaluated in mouse thyroid glands. The effects of withdrawal from chronic administration of acetazolamide were also assessed. A single injection of a large dose of acetazolamide increased iodide uptake and completely inhibited CA activity. Chronic administration of acetazolamide only slightly increased iodide uptake; CA inhibition was also less marked than after acute administration. After withdrawal of acetazolamide, iodide uptake decreased and CA activity recovered rapidly to the control levels. Chronic treatment with acetazolamide decreased the content of water and increased the contents of protein and DNA in thyroid tissues. Withdrawal of the drug resulted in an increase in Na+ and K+ contents and a decrease in water content of this gland. These data demonstrate that CA activity has an inverse relation to the iodide transport and a direct relation TO Cl- content in the thyroid. Chronic administration of acetazolamide also increased iodide uptake by the thyroid glands of hypophysectomized rats and of turtles.

Acetazolamide↗
PubMed1992

Acetazolamide in the treatment of acute mountain sickness: clinical efficacy and effect on gas exchange.

OBJECTIVE: To determine the efficacy of acetazolamide in the treatment of patients with acute mountain sickness and the effect of the drug on pulmonary gas exchange in acute mountain sickness. DESIGN: A randomized, double-blind, placebo-controlled trial. SETTING: The Denali Medical Research Project high-altitude research station (4200 m) on Mt. McKinley, Alaska. PARTICIPANTS: Twelve climbers attempting an ascent of Mt. McKinley (summit, 6150 m) who presented to the medical research station with acute mountain sickness. INTERVENTION: Climbers were randomly assigned to receive acetazolamide, 250 mg orally, or placebo at 0 (baseline) and 8 hours after inclusion in the study. MAIN OUTCOME MEASURES: An assessment of acute mountain sickness using a symptom score and pulmonary gas exchange measurements was done at baseline and at 24 hours. MAIN RESULTS: After 24 hours, five of six climbers treated with acetazolamide were healthy, whereas all climbers who received placebo still had acute mountain sickness (P = 0.015). Arterial blood gas specimens were obtained from three of the six acetazolamide recipients and all of the placebo recipients. The alveolar to arterial oxygen pressure difference (PAO2-PaO2 difference) decreased slightly over 24 hours in the acetazolamide group (-0.8 +/- 1.2 mm Hg) but increased in the placebo group (+3.3 +/- 2.3 mm Hg) (P = 0.024). Acetazolamide improved PaO2 over 24 hours (+2.9 +/- 0.8 mm Hg) when compared with placebo (-1.3 +/- 2.8 mm Hg) (P = 0.045). CONCLUSION: In established cases of acute mountain sickness, treatment with acetazolamide relieves symptoms, improves arterial oxygenation, and prevents further impairment of pulmonary gas exchange.

Acetazolamide↗
PubMed2000

[Acetazolamide--are there reasons for its revival in antiepileptic treatment?].

BACKGROUND: Since 1950 the carbonic anhydrase inhibitor acetazolamide has been used as an antiepileptic drug. Because of its tolerance developing properties, acetazolamide has probably been bypassed by the new antiepileptic drugs on the market. However, when taken for 14 day periods with one week's stop in between, acetazolamide is still of value in the treatment of epilepsy. MATERIAL AND METHODS: The paper discusses acetazolamide and its present use in antiepileptic treatment in the light of existing internal control and quality assurance requirements in the medical services. RESULTS: Irrespective og type of seizure, about 90% of patients have an initial reliable effect from acetazolamide, though it is uncertain how long the effect will last after repeated periods of use. As an additional drug, acetazolamide may be particularly well suited for women with menses-related seizures. INTERPRETATION: Acetazolamide may be the drug of choice when drug interaction is a problem, when rapid onset of effect is wanted, or when an additional drug is needed for a short period of time only.

Acetazolamide↗
PubMed2000

Acetazolamide opens the muscular KCa2+ channel: a novel mechanism of action that may explain the therapeutic effect of the drug in hypokalemic periodic paralysis.

Acetazolamide is a thiazide derivative clinically used in skeletal muscle disorders related to altered K+ homeostasis such as the periodic paralyses. The mechanism of action responsible for the therapeutic effects of the drug is still unknown, however. In the present work, we investigated the mechanism of action of acetazolamide in the K-deficient diet rat, an animal model of human hypokalemic periodic paralysis (hypoPP). The in vivo administration of 2.8- and 5.6-mg/kg(-1)/day(-1) concentrations of acetazolamide to K-deficient diet rats prevented paralysis and depolarization of the fibers induced by insulin. In the acetazolamide-treated animals, intense sarcolemma Ca2+-activated K+ channel (KCa2+) activity was recorded. Acetazolamide also restored the serum K+ levels to control values. The concentrations of acetazolamide needed to enhance the KCa2+ current by 50% in vitro were 6.17 and 4.01x10(-6) M at -60 and +30 mV of membrane potentials, respectively. In normokalemic animals, the thiazide derivative enhanced the KCa2+ current with similar efficacy. Our data demonstrate that the therapeutic effects of acetazolamide in the K-deficient diet rats and possibly in human hypokalemic periodic paralysis patients can be mediated by activation of the KCa2+ channel.

Acetazolamide↗
PubMed2000

Interaction and transport of thiazide diuretics, loop diuretics, and acetazolamide via rat renal organic anion transporter rOAT1.

The renal tubular secretion of thiazides and loop diuretics via the organic anion transport system in renal tubules is required for them to reach their principal sites of action. Similarly, acetazolamide, a diuretic clinically administered for glaucoma, is excreted from the kidney by glomerular filtration and tubular secretion. In this study, we investigated the interaction and transport of these diuretics via the rat renal organic anion transporter rOAT1 by using Xenopus laevis oocyte expression system. p-[(14)C]Aminohippurate (PAH) uptake by rOAT1-expressing oocytes was inhibited in the presence of a thiazide (chlorothiazide, cyclothiazide, hydrochlorothiazide), a loop diuretic (bumetanide, ethacrynic acid, furosemide), or a carbonic anhydrase inhibitor (acetazolamide, ethoxzolamide, methazolamide). Dixon plot analysis demonstrated that the inhibition constant (K(i)) value was 1.1 mM for acetazolamide, 150 microM for hydrochlorothiazide, 9.5 microM for furosemide, and 5. 5 microM for bumetanide. Kinetic analysis revealed that acetazolamide inhibited rOAT1 competitively and that inhibition style of furosemide was a mixture of competitive and noncompetitive. [(14)C]PAH efflux was significantly enhanced when the rOAT1-expressing oocytes were incubated in the presence of unlabeled PAH, alpha-ketoglutarate, acetazolamide, chlorothiazide, or hydrochlorothiazide. rOAT1 stimulated acetazolamide uptake, which was inhibited by probenecid. Although the loop diuretics had little trans-stimulation effect on [(14)C]PAH efflux via rOAT1, the rOAT1-mediated furosemide uptake was observed. These findings suggest that rOAT1 contributes, at least in part, to the renal tubular secretion of acetazolamide, thiazides, and loop diuretics.

Acetazolamide↗
PubMed2004

Oxygen extraction fraction and acetazolamide reactivity in symptomatic carotid artery disease.

OBJECTIVE: It has been proposed that cerebral blood flow (CBF) response to acetazolamide may be reduced according to the degree of autoregulatory vasodilation in regions with normal oxygen extraction fraction (OEF), whereas the CBF response may be absent in regions with increased OEF where vasodilation may be maximal in response to reduced perfusion pressure. The objective of this study was to test this hypothesis. METHODS: Positron emission tomography (PET) was used to study 30 symptomatic patients with carotid artery steno-occlusive lesions. CBF at baseline and 10 minutes after an intravenous injection of 1 g acetazolamide was measured. The correlation between the change in CBF during acetazolamide administration and the baseline value of OEF in the affected hemisphere was examined. RESULTS: The baseline OEF value was inversely and non-linearly correlated with the percentage change in CBF during acetazolamide administration (R(2) = 0.25, p = 0.02). There was an upward trend of OEF with diminishing acetazolamide response below a critical level around zero response. Acetazolamide response less than 6.65% over baseline (sensitivity 100%, specificity 89%, positive predictive value 50%, negative predictive value 100%) was established as most helpful in predicting abnormally high OEF. CONCLUSIONS: The inverse, non-linear relationship between OEF and CBF response to acetazolamide suggests that these two measurements may not identify haemodynamic impairment in the same patients.

Acetazolamide↗