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PubMed1994

High-dose methylprednisolone and acetazolamide for visual loss in pseudotumor cerebri.

We treated four patients who had acute, severe visual loss associated with pseudotumor cerebri with intravenous methylprednisolone (250 mg four times per day) for five days followed by an oral taper, in combination with acetazolamide and ranitidine. In addition to high-grade disk edema, one patient had serous detachment of both maculas and lipid deposition, one had a unilateral macular star, and one had a monocular branch retinal artery occlusion. These three patients experienced rapid and lasting improvement in visual acuity, visual field, papilledema, and symptoms. Vision of the fourth patient did not improve, requiring optic nerve sheath fenestration for chronic papilledema. Transient acne developed in one patient. This regimen is a safe, effective treatment of acute, severe visual loss associated with florid papilledema of pseudotumor cerebri. Lack of immediate improvement is an indication for optic nerve sheath decompression.

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PubMed1997

Cerebral vascular reactivity assessed with acetazolamide single photon emission computer tomography scans before and after carotid endarterectomy.

BACKGROUND AND METHODS: In 64 patients, cerebral perfusion and vascular reactivity were assessed before and after carotid endarterectomy (CEA) using acetazolamide (ACZ)-enhanced single photon emission computer tomography (SPECT). Twenty-five patients were asymptomatic, whereas the remainder were symptomatic. Sixty-one patients had a > or = 70% ipsilateral internal carotid artery stenosis. RESULTS: Fifty SPECT scans revealed decreased vascular reactivity. Twenty-three showed infarcts. Fourteen patients had normal studies. Twenty of the SPECT scans of asymptomatic patients demonstrated poor vascular reactivity. After CEA, 39 patients had improved ipsilateral vasoreactivity. In 12 patients, contralateral improvement was also found. CONCLUSION: ACZ-enhanced SPECT scans, by assessing cerebral perfusion and vascular reactivity, may help to identify patients at risk of stroke should perfusion further diminish. Postoperative studies confirm improvement in vascular reactivity. ACZ-enhanced SPECT scans may provide objective evidence for the selection of patients with a high-grade asymptomatic carotid stenosis for CEA.

Acetazolamide↗
PubMed1995

Effect of acetazolamide on intracellular pH and bicarbonate transport in bovine corneal endothelium.

Carbonic anhydrase inhibitors are known to inhibit fluid transport by the corneal endothelium. This phenomenon could be due to a combination of effects involving disruption of intracellular pH regulation, reduced gradients for diffusion of CO2, substrate limitation to HCO3- transport systems or direct inhibition of membrane HCO3- transport. We examined the effects of the carbonic anhydrase inhibitor, Acetazolamide (ACTZ), on intracellular pH (pHi) and HCO3- transport in cultured bovine corneal endothelium. The pHi was measured utilizing the pH sensitive fluorescent dye, BCECF. Na+:HCO3- cotransport and Cl-/HCO3- exchange activities were studied by measuring the HCO3(-)-dependent flux of Na+ and Cl-, respectively. Na+ and Cl- fluxes were measured using the ion-sensitive dyes SBFI and SPQ, respectively. Application of 100 or 500 microM ACTZ to cells perfused under HCO3(-)-rich conditions, significantly reduced steady-state pHi by 0.06 +/- 0.01 (n = 14, P < 0.05). ACTZ also eliminated rapid pHi transients due to CO2 diffusion, significantly slowed the initial rate of pHi changes (50 +/- 10% of control, n = 7, P < 0.05) secondary to Na+:HCO3- cotransport or Cl-/HCO3- exchange (37 +/- 1% of control, P < 0.05, n = 7). However, the flux of the cotransported ions, Na+ and Cl-, and the steady-state levels of these ions were not affected by ACTZ. We conclude that the drop in steady-state pHi, the elimination of CO2 induced pHi transients and the slowed pHi changes secondary to HCO3- transport were due to inhibition of cytosolic carbonic anhydrase by ACTZ, i.e. slowing the equilibrium among CO2, HCO3- and H+ and not due to limitation of substrate availability or direct inhibition of the membrane transporters.

Acetazolamide↗
PubMedDate not supplied

Anticonvulsant activity of analogues of acetazolamide.

The anticonvulsant activity of 5-tertbutyloxycarbonylamido-1,3,4-thiadiazole-2-sulfonamide (B-H2ats) and 5-amino-1,3,4-thiadiazole-2-sulfonamide (Hats) was compared in mice, to that of acetazolamide (H2acm). These compounds exhibit potent anticonvulsant activity and low minimal motor impairment.

Acetazolamide↗
PubMed1979

Hydrocephalus in tuberculous meningitis in children: treatment with acetazolamide and repeated lumbar puncture.

Increased intracranial pressure was found in 36 of 49 children with tuberculous meningitis. Four patients who presented with acute onset died early. Eight patients with obstructive hydrocephalus were treated surgically. In the 24 patients who had communicating hydrocephalus and were treated with acetazolamide and repeated lumbar punctures, treatment was successful in all but two, in whom shunt surgery was needed.

Acetazolamide↗
PubMed1985

Management of hydrocephalus in infancy: use of acetazolamide and furosemide to avoid cerebrospinal fluid shunts.

Despite its effectiveness, cerebrospinal shunting for hydrocephalus continues to be accompanied by considerable complications and morbidity. Medical therapy with acetazolamide 100 mg/kg/day and furosemide 1 mg/kg/day can be an effective alternative to shunting by halting progression of hydrocephalus until such time as sutures can become fibrosed and spontaneous arrest can occur. In an appropriately selected population older than 2 weeks with hydrocephalus of varied origin, our success rate in avoiding shunting is greater than 50%. The dramatic difference between the number of hospitalizations of patients with shunts and those treated medically, and the potential to avoid shunt dependence would appear to make an initial trial with medical therapy worthwhile.

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PubMed2002

Acetazolamide challenge test using semiquantitative 123 I-IMP SPECT for detection of cerebral misery perfusion.

The accuracy of the acetazolamide (ACZ) challenge test using semiquantitative SPECT in detecting Stage II hemodynamic failure, i.e. cerebral misery perfusion, in patients so diagnosed with PET has yet to be determined. This study was carried out in 53 patients who had a unilateral occlusion or severe stenosis of their cerebral artery. Asymmetry index (AI) was used to determine relative CBF distribution on each SPECT image. DeltaAI (regional vasodilatory capacity) values were compared with the values of several PET parameters. We also repeated SPECT and PET studies in 15 patients after a mean interval of 2.6 years from entry. The correlation between changes in DeltaAI and PET data were examined. The DeltaAI value closely correlated with the ipsilateral OEF value (r=-0.64, p<0.001). Sensitivity-specificity curve analysis revealed that the optimal cut-off value for detecting Stage II hemodynamic failure was -13.5% of DeltaAI, at which point the diagnostic accuracy was 82%. In follow-up studies, changes in DeltaAI correlated significantly with changes in OEF values (r=-0.68, p<0.01). Semiquantitative SPECT examination with ACZ challenge detects Stage II hemodynamic failure with a diagnostic accuracy of 82%. An improvement in reduced vasodilatory capacity as determined by SPECT coincides with a reduction in OEF values.

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PubMed2003

A novel insertion mutation of acetazolamide-responsive episodic ataxia in a Japanese family.

We report a Japanese family with acetazolamide-responsive episodic ataxia. The proband was a 41-year-old woman with interictal nystagmus. She experienced recurrent attacks of loss of equilibrium and loss of coordination of the extremities accompanied by dysarthria and nausea beginning at about 10 years old. These episodes usually lasted for several hours two or three times a week. Direct sequence of CACNA1A demonstrated a novel insertion mutation in the patient and her father. This mutation is estimated to cause early stop of the gene transcription, producing a truncated protein. This is the first report of episodic ataxia type 2 of which the mutation was identified in a Japanese family.

Acetazolamide↗
PubMed1998

The effects of acetazolamide on arterial pressure variability during REM sleep in the rat.

During rapid eye movement (REM) sleep, the arterial pressure (AP) undergoes large fluctuations in the rat, cat, and other mammals, including humans, and it has been suggested that this effect originates in the forebrain. In addition, acetazolamide (ACTZ), a carbonic anhydrase inhibitor, is known to be effective in the treatment of central sleep apnea or epilepsy. The aim of the present study was to analyze the effects of ACTZ on EEG theta rhythm and AP variability during REM sleep in rats. Treatment consisted of intraperitoneal injection of 5 mg of ACTZ in 0.5 mL of saline (n = 6) or 0.5 mL of vehicle alone (n = 6). We then recorded and analyzed the mean AP (MAP) variations during different sleep phases, using a telemetric system. Our results show: 1) Significant decreases in the coefficient of variation of MAP, in the very-low frequency (0.025 - 0.225 Hz) component of the power spectral density of the AP and in theta frequency in the electroencephalogram, were seen in the ACTZ-treated group during REM sleep compared with controls, whereas no significant difference was found between the two groups in non-REM sleep. There was no significant difference in sleep duration, average MAP, and heart rate between the groups. Our data suggest that ACTZ may act as a stabilizing factor preventing AP fluctuations during REM sleep.

Acetazolamide↗
PubMed1998

Central sleep apnea after interrupting longterm acetazolamide therapy.

One month administration of acetazolamide (ACET) (at sea level) improves periodic breathing and decreases the number of central apneas (CA) (De Backer et al., 1995 Am. J. Respir. Crit. Care Med. 151, 87-91) in nonhypercapnic central apnea syndrome. It remains unclear whether cessation of therapy would provoke recurrence of symptoms. In the present study we evaluated the number of CA after 1 and 6 months interruption of ACET therapy. Eight patients with central sleep apnea were included [central apnea index (CAI) > 5 or apnea and hypopnea index (AHI) > 10 and obstructive apnea index (OAI) < 5]. Polysomnography was repeated once after 1 month treatment (N2), after 1 month off treatment (N3) and after 6 months off treatment. CAI (25 +/- 10 at N1) decreased during N2 (4 +/- 2) and N3 (5 +/- 3) and remained low after N4 (3 +/- 1). However an increase in the number of obstructive apneas and central hypopneas could be observed together with a shift from central apnea to hypopnea after N4. Maybe ACET induces a long lasting resetting of the CO2 threshold which is still present after interruption of the therapy.

Acetazolamide↗
PubMed2000

Medroxyprogesterone acetate with acetazolamide stimulates breathing in cats.

Both medroxyprogesterone acetate (MPA) and acetazolamide (ACET) increase ventilation. Combined administration of these agents could result in an additional improvement of blood gases, for example in patients with chronic obstructive pulmonary diseases. The aim of this study in anaesthetized female (ovariohysterectomized, pre-treated with 17-beta-estradiol) cats was to compare the effects on the CO2 response curve of MPA alone (4 microg kg(-1), i.v.) with those after MPA followed by ACET (4 mg kg(-1) i.v.). We performed dynamic end-tidal CO2 forcing and analysed the data with a two-compartment model comprising a fast peripheral and slow central compartment, characterized by CO2 sensitivities (Sp and Sc, respectively) and a single offset (the apnoeic threshold B). MPA reduced Sp from 0.22 +/- 0.09 (mean +/- S.D.) to 0.13 +/- 0.06 L min(-1) kPa(-1) (P < 0.01) and Sc from 1.01 +/- 0.38 to 0.88 +/- 0.32 L min(-1) kPa(-1) (P < 0.01). B decreased from 4.02 +/- 0.27 to 3.64 +/- 0.42 kPa (P < 0.01). Subsequent administration of ACET reduced Sp and Sc further to 0.09 +/- 0.06 and to 0.70 +/- 0.49 L min(-1) kPa(-1) (P < 0.01), respectively. The apnoeic threshold decreased further to 2.46 +/- 1.50 kPa (P < 0.01). Because both treatments reduced ventilatory CO2 sensitivity, we conclude that a simulating effect on ventilation is due to a decrease in the apnoeic threshold. Combined administration of MPA and ACET may lead to larger increases in ventilation than treatment with either drugs alone.

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PubMed2005

Measurement of cerebral reserve capacity using acetazolamide loading xenon CT CBF before carotid endarterectomy.

BACKGROUND AND PURPOSE: Brain swelling and/or hemorrhage can occur after carotid endarterectomy. This phenomenon is called the hyperperfusion syndrome. Several factors contribute to this syndrome. One is reperfusion in a maximally dilated vessel which means disappearance of cerebral reserve capacity (CRC). The aim of the study was to determine whether CRC measurement was useful for intraoperative and postoperative management of carotid endarterectomy. PATIENTS AND METHODS: We studied 64 cases (male 53, female 11), 49-79 years. CRC was measured preoperatively using acetazolamide loading Xenon CT CBF examination (XeCT). Hypothermia (34-35 C) was induced during surgery in a patient with no CRC. Anesthesia was maintained the night after surgery and the systolic blood pressure was controlled below 120 mmHg. RESULTS: CRC was absent in 10 patients. Postoperative CT did not reveal any hemorrhage or brain swelling. One patient experienced a transient restless state. DISCUSSION: and conclusions: Cerebral hyperperfusion syndrome has been reported in 0.3 approximately 6.0% of patients following carotid endarterectomy (vs 1.6% in our study without hemorrhage or brain swelling). These data suggest that information on CRC could be useful for selection and perioperative management of patients during carotid endarterectomy.

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PubMed2002

Acetazolamide: future perspective in topical glaucoma therapeutics.

Through this review it is contemplated that acetazolamide (ACZ), an age-old treatment for glaucoma with a myriad of side effects and inadequate topical effectiveness, may be formulated into a topically effective agent by utilizing various newer formulation approaches of ocular drug delivery. Even though it has a poor solubility and penetration power, various studies mentioned in the review indicate that it is possible to successfully formulate topically effective ACZ by using: (i) high concentration of the drug, (ii) surfactant gel preparations of ACZ, (iii) ACZ loaded into liposomes, (iv) cyclodextrins to increase the solubility and hence bioavailability of ACZ, and (v) viscolyzers and other polymers either alone or in combination with cyclodextrins. With the advent of newer topical carbonic anhydrase inhibitors (CAIs) like dorzolamide and brinzolamide, a localized effect with fewer side effects is expected. But whenever absorbed systemically, a similar range of adverse effects (attributable to sulphonamides) may occur upon use. Furthermore, oral ACZ is reported to be more physiologically effective than 2% dorzolamide hydrochloride administered topically, even though in isolated tissues dorzolamide appears to be the most active as it shows the lowest IC(50) values for CA-II and CA-IV [M.F. Surgue, J. Ocular Pharmacol. Ther. 12 (1996) 363-376]. Hence, there exists considerable scope for the development of more/equally effective and inexpensive topically effective formulations of ACZ. The use of various formulation technologies discussed in this review can provide a fresh impetus to research in this area.

Acetazolamide↗
PubMed2002

Long-term effectiveness and side effects of acetazolamide as an adjunct to other anticonvulsants in the treatment of refractory epilepsies.

The long-term effectiveness of acetazolamide (AZA) and its side effects, especially the formation of renal calculi, were investigated in a prospective study when AZA was used as an adjunct to other antiepileptic drugs in the treatment of refractory epilepsies. The subjects comprised 37 patients aged from 1 to 17 years (mean age, 8 years and 1 month) whose seizures were hard to control with the use of two or more drugs among sodium valproate, carbamazepine and clonazepam. Thirty-two of the 37 patients were complicated with mental retardation. A daily dose of 10mg/kg of AZA was first administered and then the dosage was increased up to 20mg/kg based on the clinical response and side effects. The maintenance daily dosage of AZA (12.2+/-4.2mg/kg) produced a steady-state plasma concentration of 6.2+/-4.5 microg/ml. Among the 37 patients, complete seizure control for more than 3 years was obtained in four patients. Although there were no significant differences, all of the four patients were classified as having symptomatic localization-related epilepsies. Seizures recurred in five after complete remission for at least 6 months, and six showed >50% decrease in seizure frequency for more than 6 months after the introduction of AZA. Twenty-eight patients, who were taking AZA for 10 months to 14 years (mean, 6 years and 5 months), were examined for the formation of renal calculi. None of them showed evidence of renal calculi. This study reinforces the idea that AZA may be a useful adjunct drug in selected patients with refractory symptomatic localization-related epilepsies.

Acetazolamide↗
PubMed1998

Subdural hygroma in association with middle fossa arachnoid cyst: acetazolamide therapy.

Intracranial arachnoid cysts are cerebrospinal fluid-filled collections between arachnoid layers. While many are silent, arachnoid cysts can become symptomatic if there is sudden expansion, haemorrhage or rupture with the development of subdural hygroma or subdural hematoma. Several studies have demonstrated the association of arachnoid cysts with subdural hygroma and subdural hematoma. We describe a 9-year-old girl with a moderate-sized middle-fossa arachnoid cyst and bilateral frontal subdural hygroma presenting with raised intracranial pressure. She was treated with acetazolamide which resulted in resolution of the subdural hygroma and relief of symptomatology.

Acetazolamide↗
PubMed1998

Quantitation of acetazolamide in rat plasma, brain tissue and cerebrospinal fluid by high-performance liquid chromatography.

A simple and sensitive high-performance liquid chromatographic method for the analysis of acetazolamide (AZ) in rat blood (plasma/serum, whole blood and serum ultrafiltrate), brain tissue and cerebrospinal fluid (CSF) was described. Quantitative extraction of AZ with ethyl acetate from both buffered plasma and brain tissue homogenate (pH 8.0) was achieved. Each extract was evaporated to dryness and the residue was chromatographed on a reversed-phase column. CSF was directly analysed without extraction step. The limits of detection were 0.05 microgram ml-1 for plasma, 0.02 microgram g-1 for brain tissue and 0.004 microgram ml-1 for CSF. Calibration curves were linear over the working ranges of 0.1-100 micrograms ml-1 for plasma, 0.05-50 micrograms g-1 for brain tissue and 0.025-50 micrograms ml-1 for CSF. The reproducibility of AZ assay in the rat biologic media indicated very low relative standard deviations (RSDs). The recoveries of AZ added to plasma and brain tissue were more than 96% with an RSD of less than 5%. The present method was applied to studies of plasma concentration profiles of the drug after administration and its distribution into central nervous system.

Acetazolamide↗
PubMed1999

The value of acetazolamide single photon emission computed tomography scans in the preoperative evaluation of asymptomatic critical carotid stenosis.

PURPOSE: Acetazolamide (ACZ)-enhanced single photon emission computed tomography (SPECT) scans can assess both cerebral perfusion and vascular reactivity. Patients with asymptomatic critical carotid artery stenosis were evaluated for cerebral vascular reactivity to determine the effect of extracranial occlusive disease and the effect of carotid endarterectomy (CEA) on intracerebral reactivity. METHODS: In 44 patients with asymptomatic critical carotid artery stenosis, cerebral perfusion and vascular reactivity were assessed before CEA with resting and ACZ-enhanced SPECT scans. All patients had a 70% or greater ipsilateral internal carotid artery stenosis. Preoperative ACZ-enhanced SPECT scans were obtained, usually 5 days before CEA. Postoperative ACZ-enhanced SPECT scans were obtained in 30 patients. RESULTS: Preoperative SPECT scans were asymmetric, revealing focal (n = 19) or global (n = 15) decreased reactivity in 34 patients (77%). Ten patients had symmetric or normal reactivity. After CEA, 23 patients demonstrated an improvement in reactivity ipsilateral to the side of surgery. The remaining seven patients failed to improve after surgery. CONCLUSION: Although all patients had a high-grade internal carotid stenosis, nearly a quarter of the patients had excellent intracerebral collateral flow. Only 71% of patients demonstrated improved intracerebral vasoreactivity after CEA. The lack of improvement in the other patients may have resulted from intracerebral pathology or lack of improvement in the extracranial carotid hemodynamics.

Acetazolamide↗
PubMed1999

Acetazolamide and furosemide for posthemorrhagic hydrocephalus of the newborn.

The authors evaluated the efficacy of acetazolamide (ACZ) and furosemide (FUR) in avoiding ventricular shunting procedures in preterm infants with posthemorrhagic hydrocephalus (PHH) and increased intracranial pressure (ICP). Preterm infants were screened for PHH (defined as ventriculomegaly [VM] and increased ICP measured with the Ladd fiberoptic monitor). PHH infants were randomized to ACZ and FUR treatment or serial lumbar puncture (LP) and monitored until not receiving medications or having undergone shunting. Of 69 infants with IVH screened for the study, 39 never developed VM, 14 developed VM, without increased ICP, and 16 developed PHH. Ten PHH infants were randomized to ACZ and FUR treatment and six to serial LP. Nine (90%) of the 10 infants assigned to the ACZ and FUR group avoided shunting. Nephrocalcinosis developed in a significant proportion of treated infants. Three (50%) of the six LP group infants did not require shunting procedures (P = 0.118). The authors conclude that ACZ and FUR therapy is useful in the treatment of preterm infants with PHH. Because a significant number of infants treated with both ACZ and FUR developed nephrocalcinosis, close monitoring for increased calcium excretion in the urine, or use of ACZ without FUR, is advised.

Acetazolamide↗