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PubMed2003

Differences in acetazolamide vasoreactivity in patients with acute and chronic occlusion of the internal carotid artery.

Using a xenon-enhanced computed tomography (Xe-CT) system, we measured cerebral blood flow (CBF) and acetazolamide vasoreactivity in 3 major vascular territories, the thalamus and putamen on both sides in 3 groups of patients undergoing the balloon occlusion test (BOT), with internal carotid occlusion (ICO) and with open carotids.In the ICO group, although the CBFs on the occluded side were similar to those in the BOT group, the vasoreactivity was significantly higher. The CBFs on the contralateral side were lower than those in the BOT group, but the vasoreactivity was similar. The vasoreactivity of the MCA on the occluded side mostly correlated with that in the other areas, similar to the results obtained in the open carotid group, although it was poorly correlated with other areas in the BOT group. Carotid artery occlusion may reduce CBF in a large area with restoration of vasoreactivity in the chronic stage.

Acetazolamide↗
PubMed1996

Use of transcranial Doppler sonography and acetazolamide test to demonstrate changes in cerebrovascular reserve capacity following carotid endarterectomy.

OBJECTIVES: To assess the effect of carotid endarterectomy on cerebrovascular reserve capacity. METHODS: Cerebral blood flow velocity (CBFV) and cerebrovascular reserve capacity (CVRC) were measured by transcranial Doppler sonography (TCD) and acetazolamide test in 40 patients who underwent uncomplicated unilateral carotid endarterectomy (CEA). Indication for operation was limited to stenoses > 70% as documented by angiography and/or Duplex scanning. The TCD studies were carried out 6 days (range 1-14 days) before and 8 days (range 5-12 days) after endarterectomy. RESULTS: Before endarterectomy, resting CBFV values and CVRC in the 40 patients were significantly different between the operated (51 +/- 19 cm/s; 20 +/- 16%) and the non-operated (60 +/- 19 cm/s; 34 +/- 24%) hemisphere (p < 0.05;p < 0.01). After CEA the overall increase of resting CBFV of the operated side was highly significant with preoperative CBFV values of 51 +/- 19cm/s and postoperative values of 62 +/- 15 cm/s (p < 0.01). Cerebrovascular reserve capacity after operation was increased on both sides significantly (non-operated side: from 34 +/- 24% to 43 +/- 19%, p < 0.05; operated side: from 20 +/- 16% to 51 +/- 18%, p < 0.001), and the preoperative asymmetry was no longer present. CONCLUSIONS: CEA has a beneficial effect on the cerebral circulation in most patients, even those who presented with asymptomatic carotid artery stenosis. Since CVRC has been assessed in the early postoperative period, our findings also suggest that cerebral vascular adaption occurs within 2 weeks after CEA.

Acetazolamide↗
PubMed1984

Familial periodic ataxia responsive to acetazolamide.

Two cases, a father and son, of recurrent cerebellar ataxia in the same family are reported, suggesting a familial trait for the dysfunction. In the older male the onset of each episode (30-90 min.) was signalled by dysarthria which then progressed towards gait ataxia; the son presented closely similar clinical symptoms. Physical examination and blood chemistry revealed no obvious neurological deficit or biochemical abnormalities, with the exception of I-III and III-IV evoked auditory wave interpeak latencies, which were found markedly abnormal on the left side in the father but not in the son; the EEG of both individuals showed some diffuse, slow wave abnormalities. A low dose of acetazolamide, 250 mg daily, has successfully repressed recurrence of the attacks over the past six months. Temporary withdrawal for 14 days of the carbonic anhydrase inhibitor in the father coincided with two observed ataxic episodes.

Acetazolamide↗
PubMed1977

Interaction of acetazolamide and 4-nitrothiophenolate ion with bivalent metal ion derivatives of bovine carbonic anhydrase.

The stability and rate constants for the interaction of acetazolamide (diamox) and 4-nitrothiophenolate ion (NTP) with the bivalent Mn, Co, Ni, Cu and Cd forms of bovine carbonic anhydrase have been measured by utilizing the distinct visible spectra of each metalloenzyme-NTP adduct. Differing stabilities of the various NTP and (particularly) diamox complexes reside mainly in varying values for the dissociation rate constants (kd). Intrinsic formation rate constants (for the acid form of the enzyme reacting with the basic form of the ligand) are uniformly high (greater than or equal 2 X 10(7) M-1 s-1 at 25 degrees C). Invariance of kd with pH and a bell-shaped log K-pH profile with the Cu-enzyme adducts are features observed previously with the native enzyme. Binding of NTP with the Cu and Cd metalloenzymes is stronger than to the native form.

Acetazolamide↗
PubMed1992

Acetazolamide-like carbonic anhydrase inhibitors with topical ocular hypotensive activity.

New carbonic anhydrase (EC 4.2.1.1) inhibitors were synthesized as potential drugs for the topical treatment of glaucoma. They were obtained by substituting the acetyl group of acetazolamide and methazolamide with bicarboxylic acids of different chain length (C4-C6). The terminal carboxyl was either kept free or esterified with alcohols of different size (C1-C12). A gamma-aminovaleric derivative was also prepared. All compounds proved active as carbonic anhydrase inhibitors in vitro, with an average IC50 of about 0.5 microM. Some proved also to be topically active in vivo in lowering the artificially elevated intraocular pressure in rabbits. The most active compound, carrying a succinic acid side chain, is the most soluble in aqueous buffers. Its duration of action is about 8 h and it is under evaluation as a topical antiglaucoma drug. It is hypothesized that the duration of action could be longer in compounds having both the same high water solubility and partition coefficient.

Acetazolamide↗
PubMed2002

Cerebrovascular reactivity in patients under long-term acetazolamide treatment.

BACKGROUND AND PURPOSE: The acetazolamide (AZA) test is a well-accepted method for measuring the vascular reactivity of the cerebral arteries. In order to investigate the nature of this reactivity after long-term daily AZA treatment, the cerebral blood velocity (CBV) was measured using transcranial Doppler in patients under continuous AZA treatment after a single AZA 1 g intravenous (IV) dose. METHODS: Thirteen patients (eight women, five men) on long-term daily AZA (750 mg/day, mean treatment duration 68 +/- 12+ months) were included in the study. The CBV of the middle cerebral artery (MCA) and the basilar artery (BA), including the values of peak velocity, mean velocity and pulsatility index (PI) were measured. The examination was performed twice - with the initial IV administration of AZA and 20 min later. The results were compared with those of 10 age matched volunteers. RESULTS: A consistent significant increase of CBV in the right and left MCA (P < 0.001 for both arteries) was found in all study participants. A highly significant decrease of peak CBV in the BA (P < 0.001) was found in the post-AZA velocities of the patient's group. In the control group, a consistent significant increase in all post-AZA tests was demonstrated (P < 0.001). CONCLUSIONS: A mild elevation of blood velocity in the MCAs concomitant with a highly significant decrease of velocity in the BA was present in all examined patients. These patterns of CBV changes indicate the presence of a 'steal phenomenon' from the posterior to the anterior circulation and stress the necessity for caution when evaluating the indications for performance of the AZA test in patients under continuous AZA therapy.

Acetazolamide↗
PubMed1993

Indomethacin abolishes cerebral blood flow increase in response to acetazolamide-induced extracellular acidosis: a mechanism for its effect on hypercapnia?

Indomethacin is known to attenuate quite markedly the increase in CBF during hypercapnia. Hypercapnia is, in all likelihood, mediated by the acid shift at the level of the smooth muscle cells of the cerebral arterioles. We therefore investigated the effect of indomethacin on the CBF increase caused by acetazolamide (Az), a drug that induces brain extracellular acidosis, which triggers its effect on CBF. We compared the results to the inhibitory effect of indomethacin on the CBF increase during hypercapnia. Indomethacin but not diclofenac, another potent cyclooxygenase inhibitor, was found to block almost completely the CBF increase caused by Az-induced extracellular acidosis or by CO2, but it did not influence the CBF increase produced by sodium nitroprusside or papaverine. The results suggest that indomethacin exerts its action on CO2 reactivity by a nonprostaglandin-mediated mechanism that directly interferes with the regulation of cerebrovascular tone mediated by extracellular pH.

Acetazolamide↗
PubMed1994

The effect of acetazolamide on regional cerebral blood oxygenation at rest and under stimulation as assessed by MRI.

The sensitivity of gradient echo magnetic resonance imaging (MRI) to changes in cerebral blood oxygenation (CBO) has been introduced for mapping functional brain activation. Here, we report that this approach allows monitoring autoregulation in the human brain under vasodilatory stress. Following the administration of acetazolamide, signal intensities of deoxyhemoglobin-sensitive images increased in cortical and subcortical gray matter and to a lesser extent in white matter. This result reflects a venous hyperoxygenation stemming from an increase in cerebral perfusion with oxygen consumption remaining constant. In addition, pharmacologic induction of vasodilation attenuated activity-related MRI signal changes in the visual cortex under photic stimulation. Although intersubject variability was high, this finding indicates individually persisting autoregulatory responsiveness to functional challenge despite an "exhausted" reserve capacity. It is suggested that recording CBO by MRI will foster our understanding of modulation of vasomotor tone and cerebral perfusion. Furthermore, this technique may prove valuable for assessing the cerebrovascular reserve capacity in patients with carotid artery occlusive disease.

Acetazolamide↗
PubMed1987

Effect of acetazolamide on renal metabolism and ammoniagenesis in the dog.

The effect of acetazolamide (ACZ) on renal metabolism and ammoniagenesis was studied in the dog in vivo and in vitro. ACZ was administered to 10 dogs with normal acid-base status and five with chronic metabolic acidosis induced by NH4Cl. In both groups of dogs, the acute administration of ACZ markedly reduced the urinary excretion of ammonium (from 33 to 10 in normal dogs and from 100 to 23 mumoles/100 ml GFR in acidotic dogs) whereas its release into the renal vein was increased in a reciprocal fashion (from 69 to 95 in normal dogs and from 91 to 152 mumoles/100 ml GFR in acidotic dogs). ACZ did not change the total ammonium production nor the renal glutamine utilization. The renal utilization or production of glutamate, alphaketoglutarate, alanine and citrate also remained unchanged. Despite a marked urinary alkalinization, citraturia remained minimal. However, the renal cortical concentrations of glutamine, glutamate, succinate, fumarate, malate, aspartate and phosphoenolpyruvate fell following ACZ administration, especially in acidotic dogs showing rapid renal utilization of glutamine. ACZ had no effect on the same metabolites in the kidney of normal dogs even when lactate utilization was enhanced by lactate infusion. This study demonstrates that an accelerated ammoniagenic flux can proceed in the dog kidney without the renal cortical changes produced by metabolic acidosis in this species. In vitro, using dog tubules, a selective effect of ACZ on glutamine metabolism as compared to lactate was observed. ACZ reduce the rate of the reactions catalyzed by alphaketoglutarate dehydrogenase and by succinyl CoA synthetase. Other enzymes of the ammoniagenic and gluconeogenic pathways (glutaminase, GLDH, malic enzyme, PEPCK) were not changed by ACZ. The metabolic effects of ACZ observed in the intact kidney in vivo or with tubules in vitro may be in part related to the effect of ACZ on these enzymes critical for the ammoniagenic process.

Acetazolamide↗
PubMed1990

Acetazolamide-insensitive carbonic anhydrase activities in liver and tonic skeletal muscle of adult male rats with streptozotocin-induced diabetes mellitus.

One of the four discrete isoenzymes of carbonic anhydrase hitherto characterized, CA III, has the lowest turnover rate and the greatest resistance to inhibition by sulphonamides. Streptozotocin-induced diabetes mellitus resulted in a reduction in acetazolamide-resistant activity of carbonic anhydrase in the liver, but not in tonic skeletal muscle, of adult male rats. The hepatic activity declined with apparent first-order kinetics [calculated rate constant (k) 0.089 day-1] to a minimum of approx. 6% of control values; the reduction in activity was moderated by administration of insulin.

Acetazolamide↗
PubMed2000

Paroxysmal dystonia induced by exercise and acetazolamide.

We report a case of a 40-year-old woman with dystonic attacks precipitated by slight exercise. Episodes lasted 2-5 min and were not precipitated by sudden movements or by being startled, drinking alcohol, coffee or tea, or by stress. Secondary dystonia was ruled out and brain magnetic resonance imaging (MRI) was unremarkable. Routine and video electroencephalogram (EEG) during and between attacks were normal. Acetazolamide greatly worsened her condition, whereas gabapentin [1-(aminomethyl) cyclohexaneacetic acid] treatment markedly reduced the frequency and severity of the episodes.

Acetates↗
PubMed2001

Hypoperfusion following encephalitis: SPECT with acetazolamide.

At 4 weeks and 8 months following initial symptoms, we performed single-photon emission computed tomography (SPECT) with acetazolamide (ACZ) testing in a patient recovering from acute encephalitis, possibly acute disseminated encephalomyelitis (ADEM). Both regional hypoperfusion at baseline and diminished cerebrovascular reserve were seen after focal hyperintensities had disappeared in magnetic resonance imaging (MRI). The time course of SPECT abnormalities reflected the clinical course more closely than the time course of MRI abnormalities. Thus, persistent cerebral circulatory impairment probably contributed to cognitive and language deficits observed at the subacute stage.

Acetazolamide↗
PubMed2003

Acetazolamide as a vasodilatory stimulus in cerebrovascular diseases and in conditions affecting the cerebral vasculature.

Pathologic processes affecting the brain vessels may damage cerebral vasodilatory capacity. Early detection of cerebral dysfunction plays an important role in the prevention of cerebrovascular diseases. In recent decades acetazolamide (AZ) has frequently been used for this purpose. In the present work the mechanism of action and the previous studies are reviewed. The authors conclude that AZ tests are useful in cerebrovascular research. Further investigations are recommended to prove how impaired reserve capacity and reactivity influence the stroke risk in patients and whether these tests may indicate therapeutic interventions.

Acetazolamide↗
PubMed2001

Contrasting effects of zonisamide and acetazolamide on amygdaloid kindling in rats.

PURPOSE: Zonisamide (ZNS) and acetazolamide (AZM) are two antiepileptic drugs (AEDs) that differ in clinical efficacy. To elucidate the mechanisms of action of these compounds, we investigated their therapeutic and prophylactic effects in rats by using a kindling model of partial epilepsy. METHODS: Electrodes were implanted into the left amygdala of adult male Wistar rats. The animals were stimulated at the afterdischarge threshold until five stage 5 seizures were induced. The generalized seizure threshold was then determined. Therapeutic effects were examined in rats manifesting successive convulsions with near-threshold stimulation. To test prophylactic effects, drugs were administered intraperitoneally before daily kindling stimulation until the animal had a stage 5 seizure or reached day 18. RESULTS: ZNS (10-40 mg/kg; n=6) suppressed kindled seizures in a dose-dependent manner. Repeated administration for 7 days produced tolerance to anticonvulsive effects. AZM (25-200 mg/kg; n=7) showed limited therapeutic effect, alleviating only the clonic convulsion in stage 5 seizures and reducing afterdischarge duration. Secondary generalization was not significantly suppressed during repeated treatment (50-200 mg/kg; n=6). ZNS, 25 or 40 mg/kg (n=8), significantly retarded seizure development; 15.0 or 17.0 daily stimulations were required to produce a stage 5 seizure. AZM, 50-200 mg/kg (n=6), also retarded seizure development, with 14.0-14.8 stimulations required. CONCLUSIONS: ZNS exhibited modest therapeutic and prophylactic effects, whereas AZM showed mainly prophylactic effects. Hypotheses are presented that may explain the mechanisms of action of these drugs.

Acetazolamide↗
PubMed2001

Acetazolamide in women with catamenial epilepsy.

PURPOSE: Catamenial epilepsy is a condition characterized by an increase in seizures during particular phases of the menstrual cycle. The incidence of catamenial epilepsy varies widely, partly because of a lack of a universally adopted definition. Specific treatment options for these patients are limited. The use of acetazolamide (AZ) has been based largely on anecdotal reports demonstrating efficacy in small or poorly characterized populations. The purpose of this study was to analyze retrospectively the efficacy, safety profile, and tolerability of AZ in women with catamenial epilepsy. METHODS: Women with catamenial epilepsy identified from 1990 through 1999 were invited to participate in a retrospective telephone questionnaire addressing the relationship of seizures and the menstrual cycle and the use, efficacy, and adverse effects of AZ. Seizure outcome was classified as: seizure free (SF), significantly improved (SI), or not significantly improved (NSI). Responses to AZ were compared in women with different types of epilepsy and comparing continuous versus intermittent dosing using Fisher's exact tests. RESULTS: Twenty women were identified who had received or were currently taking AZ. The drug was given continuously in 55% and intermittently in 45% of patients. A > or =50% decrease in the seizure frequency was reported by 40% of subjects. Response rates were similar in generalized and focal epilepsy and in temporal and extratemporal epilepsy. There was no significant difference in effectiveness comparing continuous with intermittent dosing. A loss of efficacy over 6-24 months was reported by 15% of women. CONCLUSIONS: Despite our small sample and retrospective design, AZ appears to demonstrate efficacy for catamenial epilepsy.

Acetazolamide↗
PubMed2002

Effect of acetazolamide on hypericin photocytotoxicity.

The photodynamic action of hypericin (HYP) in vitro was evaluated using human leukemic HL-60 and lung carcinoma A549 cell lines. After illumination HYP (1 x 10 (-5) M) reduced the proliferation and/or survival of HL-60 and A549 cells vs. controls to almost to 0 % and 29 %, respectively. A lower concentration of HYP (1 x 10 (-6) M) decreased the proliferation and/or survival only in HL-60 cells. Non-cytotoxic concentrations of the carbonic anhydrase inhibitor acetazolamide (ACTZ) (1 x 10 (-3)-1 x 10 (-6) M) significantly potentiated these effects of HYP (1 x 10 (-6)M) in HL-60, but not in the A549 cell line. The highest concentration of ACTZ (1 x 10 (-3) M) also induced an increase of the subdiploid G 0 /G 1 population in HYP (1 x 10 (-6) M) treated HL-60 cells from 14 % to 24 %. The results indicate that the photogenerated pH drop may participate in the potentiation of the photodynamic action of HYP observed in leukemia cells.

Acetazolamide↗
PubMed2004

[Impaired cerebral autoregulation in asymptomatic patients with carotid artery stenosis: comparison of acetazolamide-SPECT and transcranial CO(2)-dopplersonography].

PURPOSE: The indication for operation in patients with asymptomatic high-grade carotid artery stenosis is still under debate. Since impaired cerebrovascular autoregulation is associated with an increased risk for ischaemic events, assessment of cerebral vascular reactivity might be a valuable selection criterion for surgery. The aim of our study was therefore to evaluate the incidence of impaired autoregulation in asymptomatic patients with acetazolamide-single photon emission computed tomography (ACZ-SPECT) and transcranial CO (2)-dopplersonography (CO (2)-TCD). Furthermore, both methods were compared in regard to results and clinical practicability. METHODS: In 42 patients with high-grade (> 70 %) asymptomatic carotid artery stenosis, cerebral perfusion and vascular reactivity were assessed with resting and ACZ-enhanced SPECT scans. In 31 of these patients the CO (2) reactivity of cerebral perfusion was determined by TCD and expressed as normalized autoregulation reserve (NAR). RESULTS: Cerebral perfusion was decreased in 14.3 %. In ACZ-SPECT 26 % and in CO (2)-TCD 28 % revealed an impaired vascular reactivity. Conformity of both methods was high (kappa = 0.93). TCD was superior in practicability, but only applicable in 81 % due to a missing temporal bone window for insonation. CONCLUSION: In accordance ACZ-SPECT and CO (2)-TCD could detect impaired vascular reactivity in a quarter of asymptomatic patients. Both TCD and SPECT could be of value for preoperative selection in this group of patients, whereby sonography is recommended for daily diagnostic work-up.

Acetazolamide↗
PubMed1990

[The effect of acetazolamide-induced, endogenous volume stress of the cerebrospinal system on intracranial pressure. Diamox--effect on intracranial pressure].

In 16 patients with possible disturbed CSF circulation longterm recording of intracranial pressure (ICP) was performed. In 9 of the 16 patients the disorder became evident after the application of an exogenous volume-pressure testing procedure. This procedure enabled a classification into a group I--disturbed CSF circulation (8 patients)--and another group II--normal CSF circulation (8 patients). During a routine Xenon-CT-CBF study all patients of both groups were given to 1 g acetazolamide (DIAMOX) intravenously. Before, during and after the administration of DIAMOX the epidural ICP was continuously measured. An increase in ICP was monitored in all patients. In group I the average initial ICP was 13.6 +/- 7.6 mmHg. The maximum ICP was reached within a time interval of 13.1 +/- 4.5 min after DIAMOX administration. At this time the mean ICP was 36.4 +/- 19.2 mmHg (p less than 0.01). The average initial ICP in group II was 6.3 +/- 4.2 mmHg. The maximum ICP was reached within a time interval of 13.6 +/- 1.1 min. At this time the mean ICP was 11.9 +/- 4.8 mmHg (p less than 0.01). In respect to the maximum ICP both groups were significantly different (p less than 0.01). Despite a considerably rising ICP up to values of about 50 to 70 mmHg in several patients of group I only 1 patient complained of being sick. Presumingly, an ICP elevation caused by vasodilatation would be better tolerated than ICP elevations due to other causes.

Acetazolamide↗