Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “ACETAZOLAMIDE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 703 records · Page 39Linked to original sources
PubMed1997

KCl reabsorption by the lower malpighian tubule of rhodnius prolixus: inhibition by Cl(-) channel blockers and acetazolamide.

Iono- and osmoregulation by the blood-feeding hemipteran Rhodnius prolixus involves co-ordinated actions of the upper and lower Malpighian tubules. The upper tubule secretes ions (Na(+), K(+), Cl(-)) and water, whereas the lower tubule reabsorbs K(+) and Cl(-) but not water. The extent of KCl reabsorption by the lower tubule in vitro was monitored by ion-selective microelectrode measurement of Cl(-) and/or K(+) concentration in droplets of fluid secreted by Malpighian tubules isolated under oil. An earlier study proposed that K(+) reabsorption involves an omeprazole-sensitive apical K(+)/H(+) ATPase and Ba(2+)-sensitive basolateral K(+) channels. This paper examines the effects acetazolamide and of compounds that inhibit chloride channels, Cl(-)/HCO(3)(-) exchangers and Na(+)/K(+)/2Cl(-) or K(+)/Cl(-) co-transporters. The results suggest that Cl(-) reabsorption is inhibited by acetazolamide and by Cl(-) channel blockers, including diphenylamine-2-carboxylate(DPC) and 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB), but not by compounds that block Na(+)/K(+)/Cl(-) and K(+)/Cl(-) co-transporters. Measurements of transepithelial potential and basolateral membrane potential during changes in bathing saline chloride concentration indicate the presence of DPC- and NPPB-sensitive chloride channels in the basolateral membrane. A working hypothesis of ion movements during KCl reabsorption proposes that Cl(-) moves from lumen to cell through a stilbene-insensitive Cl(-)/HCO(3)(-) exchanger and then exits the cell through basolateral Cl(-) channels.

Journal Article↗
PubMed1999

Response of cerebral blood flow and cerebrovascular reactivity to acetazolamide in patients with dementia and idiopathic normal-pressure hydrocephalus.

The responses of cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) to administration of acetazolamide were investigated in 16 patients with dementia and ventriculomegaly to clarify the cerebral hemodynamics in patients with idiopathic normal-pressure hydrocephalus (NPH). The mean CBF velocity in the whole brain was measured by the Patlak plot method by using technetium-99m hexamethylpropyleneamine oxime single-photon emission computerized tomography. The CVR values were obtained from the response to administration of 500 mg of acetazolamide and calculated as the percentage of change from the baseline mean CBF value. The mean CBF value was significantly reduced (p < 0.01) in six patients with (35.2 +/- 5 ml/100 g/minute) and 10 patients without (33.5 +/- 2.8 ml/100 g/minute) NPH compared with the age-matched normal controls (40.8 +/- 3.2 ml/100 g/minute), showing no significant difference. The CVR was significantly impaired in patients with NPH (0.8 +/- 1.7%; p < 0.001), whereas in patients without NPH preserved CVR (11.3 +/- 3%) was demonstrated compared with the normal controls (14.7 +/- 1.1%). In patients with NPH a significantly lower CVR (p < 0.001) was shown than in those without NPH. The CVR significantly increased (p < 0.001) after placement of a shunt in patients with NPH. Reductions in both CBF and CVR may be diagnostic indicators of NPH in patients with dementia in whom ventriculomegaly is present. In patients with dementia and idiopathic NPH both reduced CBF and extremely impaired CVR are shown. The results of the present study suggest that ischemia due to the process of NPH is responsible for the reduction of CBF and manifestation of symptoms in patients with idiopathic NPH.

Journal Article↗
PubMed1975

Hyperkalemic periodic paralysis. Effects of potassium, exercise, glucose, and acetazolamide on blood chemistry.

Effects of strenous exercise, followed by rest, and of potassium administration on blood chemistry values were studied in two patients with hyperkalemic periodic paralysis and in normal volunteers. These procedures produced attacks of flaccid paralysis that occurred concomitantly with rapid rises in serum potassium concentrations and decreases in blood glucose and inorganic phosphate levels. With the exception of the serum potassium level which rose following exercise and potassium administration, there were no changes in the blood chemistry values of the normal volunteers. During the induced attacks of paralysis, the expired breath of the patients had a very strong odor of ketosis. Results of subsequent glucose tolerance tests were abnormal. Following 24 hour administration of acetazolamide, the studies were repeated. The drug appeared to cause lesser effects of stimuli on serum potassium levels and a stabilizing effect on blood glucose levels.

Acetazolamide↗
PubMed1997

Acetazolamide reduces peripheral afferent transmission in humans.

Carbonic anhydrase has been localized in skeletal muscle and nerve, thus, inhibition with acetazolamide (ACZ) may alter nerve and/or muscle function in healthy humans. ACZ (3 oral doses 14, 8, and 2 h prior to testing) reduced isometric force (37%) and peak to peak electromyographic (EMG) amplitude (1.38 mV to 0.83 mV), while increasing EMG latency associated with a unilateral Achilles tendon-tap. Reflex recovery profiles, following a contralateral conditioning tap, were similar in both placebo and ACZ experiments. ACZ led to significant changes in Hmax/Mmax ratio (52.19/14.42 to 45.73/15.65) and H-reflex latency (34.18 +/- 2.54 ms to 35.24 +/- 2.74 ms). Motor nerve conduction velocity and maximal voluntary isometric torque (knee extensors) were unaltered by ACZ. These data suggest that inhibition of the tendon-tap reflex and associated isometric force, following ACZ, is related to impairment of synaptic integrity between la fibers of the muscle spindle and the alpha motor neuron and not impairment of the muscle spindle or force-generating capacity.

Acetazolamide↗
PubMed2001

Sodium channel inactivation defects are associated with acetazolamide-exacerbated hypokalemic periodic paralysis.

A novel mutation in a family with hypokalemic periodic paralysis is described. The mutation R672S is located in the voltage sensor segment S4 of domain II in the SCN4A gene encoding the human skeletal muscle voltage-gated sodium channel. Functional expression of the R672S channels in human embryonic kidney 293 cells revealed a small but significant hyperpolarizing shift in the steady-state fast inactivation, and a dramatic enhancement in channel slow inactivation. These two defects are mainly due to a slow recovery of the mutant channels from fast and/or slow inactivation. Our data may help explain the mechanism underlying hypokalemic periodic paralysis and the patient's worsening from acetazolamide.

Acetazolamide↗
PubMedDate not supplied

Relative bioavailability of acetazolamide tablets.

Plasma acetazolamide concentrations were determined enzymatically after administration of three tablet dosage forms and a reference solution to 12 human subjects in a crossover study. Two of the tablet products represented different lots from the same manufacturer. There were no significant differences in area under the plasma level-time curves among the four treatments. However, significant differences were found among tablets in terms of peak plasma concentration and time to reach peak concentration. These apparent differences in rate of absorption were correlated with in vitro dissolution data obtained in pH 1.5 dissolution medium.

Acetazolamide↗
PubMed1979

Nonlinear model for acetazolamide.

Intravenous bolus injections of 14C-labeled acetazolamide were made in rabbits. Plasma, urine, and washed red blood cell concentrations were measured, the latter indicating bound drug. AUTOAN and NONLIN were used to fit the plasma data to a linear two-compartment model. However, utilization of the urine and red blood cell data suggested that a nonlinear model was more appropriate. The developed nonlinear system uses a one-compartment model with two tissue-binding parameters. The system simultaneously fits three equations describing drug in the plasma, in the body, and bound to red blood cells, Six parameters were estimated. The initial plasma concentration and the maximum amount bound to tissue protein (minus red blood cell protein) correlated with dose. The dissociation constant from this protein fraction suggested that it is composed mainly of the enzyme, carbonic anhydrase. The dissociation constant for the red blood cell fraction suggested that the drug binds to other protein in addition to carbonic anhydrase. The elimination constants were quite similar, indicating little variation from one animal to another. Utilization of the concepts of site and mechanism of action in this model should be of considerable help in relating drug concentration to pharmacological resonse.

Acetazolamide↗
PubMed1979

Relationship of pharmacokinetics to pharmacological response for acetazolamide.

Acetazolamide concentration values derived from a nonlinear model system were related to two pharmacological responses in the rabbit. Kidney response was measured by monitoring urine flow and sodium elimination. Ocular response was followed using an applanation tonometer. Maximum urine flow and sodium elimination occurring immediately after injection correlated with log dose. Urine flow dropped below control values along with a rise in osmolality, suggesting the involvement of antidiuretic hormone. Sodium elimination was correlated with plasma levels. Urine pH is thought to be involved in reducing accessibility of drug to carbonic anhydrase in the kidney. Maximum ocular response also was correlated with log dose. Ocular response was related to a protein fraction, which is believed to be mainly carbonic anhydrase. However, the duration of ocular response was related to the red blood cell protein fraction. Thus, drug activity could conceivably be regulated by monitoring a tissue that is not the site of action and can be sampled readily.

Acetazolamide↗
PubMed1994

Comparison of the effects of acetazolamide and aminophylline on apnea incidence and on ventilatory response to CO2 in preterm infants.

Acetazolamide (ACTZ) reduces sleep apnea in adults exposed to high altitude and augments the ventilatory response to CO2. In order to determine the effect of ACTZ on the ventilatory response to CO2 and the incidence of apnea in preterm infants, 7 infants (BW, 1070 +/- 191 g; postnatal age, 9 +/- 7 days) were randomized to receive ACTZ (5 mg/kg/dose Q6h for 36 hr) and 7 infants (BW, 1092 +/- 292 g; post-natal age, 5 +/- 2 days) received aminophylline (AMINO; 8 mg/kg bolus then 2.5 mg/kg Q12h for 36 hr). Minute ventilation (VE), end-tidal CO2 (PETCO2), ventilatory response to CO2, number of apneic episodes (> or = 15 sec duration), and arterial blood gases were measured before and 24-36 hr after starting therapy. In the AMINO group there was a significant decrease in apnea frequency from 6 +/- 1 to 2 +/- 2 episodes over an 8 hr epoch (P < 0.05), while no significant change was observed in the ACTZ group. The end-tidal CO2 decreased significantly from 44 +/- 7 to 38 +/- 6 mmHg in the AMINO group and from 47 +/- 5 to 36 +/- 5 mmHg in the ACTZ (P < 0.05), which lead to a shift to the left of the CO2-response curve in both groups. The slope of the CO2 response curve did not change significantly in the AMINO group and decreased in the ACTZ group. There was a significant decrease of pH from 7.43 to 7.26 in the ACTZ group, whereas in the AMINO group pH increased from 7.38 to 7.44.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetazolamide↗
PubMed1985

Pathogenesis of the mouse forelimb deformity induced by acetazolamide: an electron microscopic study.

Scanning electron microscopic observations after removal of the epidermis from developing limb buds reveal a fine mesenchymal cell process meshwork (CPM). The relationship between apical ectodermal ridge (AER) development and CPM density was investigated and related to the postaxial reduction deformities induced by acetazolamide (AA). AA was given orally to pregnant mice at 9 A.M. and 4 P.M. of day 9 and 9 A.M. of day 10 (VP = 0) in a dose of 1,000 mg/kg. Forelimb ectrodactyly, especially on the right, was the most common deformity observed. Scanning electron microscopic observations showed that the AER in AA-treated right forelimb buds did not extend postaxially as far as that in controls. The postaxial region with the hypoplastic AER became defective. Scanning and transmission electron microscopic observations revealed that in control and treated right forelimb buds, the CPM underneath the typical AER was sparser than that underneath the dorsal or ventral non-ridge epidermis. However, in treated right forelimb buds, the CPM underneath a hypoplastic AER was denser than that underneath the normal AER. These findings suggest that AA-induced deformity results from a disturbance of the AER-mesenchymal interactions.

Abnormalities, Drug-Induced↗
PubMed1986

Acetazolamide does not disrupt limb regenerate morphogenesis in the salamander, Plethodon cinereus.

Acetazolamide, a potent and highly specific inhibitor of carbonic anhydrase, is teratogenic in mammalian embryos and when administered during early limb development causes unique limb defects in a time- and dose-dependent manner. The regenerating urodele limb is often considered to be a good experimental analog of limb development and, if it employs the same mechanisms of tissue interactions during pattern formation, should be susceptible to teratogens which selectively disrupt developmental limb patterning. This study demonstrates that while carbonic anhydrase inhibition is toxic to the red-backed salamander, Plethodon cinereus, it does not have the same teratogenic effect on limb regeneration as seen in mammalian limb development. Several points are considered as to why the regenerating limb, at least in this salamander species, may not be suitable for studying this class of teratogen.

Acetazolamide↗
PubMed1993

An acetazolamide-sensitive inward chloride pump in vascular smooth muscle.

In smooth muscle cells, which have a small but significant chloride ion permeability, Cl:HCO3 exchange and (Na+K+Cl) cotransport are known to act as inwardly directed chloride pumps. However, even allowing for overestimation of [Cl]i due to intracellular interference with the Cl-recording electrodes, there remained a residual accumulation of chloride in rat arterial smooth muscle under conditions in which neither of these processes is operative. Manipulation of [Cl]i and Cl permeability using pharmacological agents whilst monitoring both Em and [Cl]i showed that an acetazolamide-sensitive mechanism, perhaps a Cl-dependent ATPase, is the third pathway for Cl accumulation.

Acetazolamide↗
PubMed1998

Crystal structure of carbonic anhydrase from Neisseria gonorrhoeae and its complex with the inhibitor acetazolamide.

The crystal structure of carbonic anhydrase from Neisseria gonorrhoeae has been solved to a resolution of 1.78 A by molecular replacement using human carbonic anhydrase II as a template. After refinement the R factor was 17.8% (Rfree=23.2%). There are two molecules per asymmetric unit (space group P21), but they have essentially identical structures. The fold of the N. gonorrhoeae enzyme is very similar to that of human isozyme II; 192 residues, 74 of which are identical in the two enzymes, have equivalent positions in the three-dimensional structures. This corresponds to 85% of the entire polypeptide chain of the bacterial enzyme. The only two cysteine residues in the bacterial enzyme, which has a periplasmic location in the cell, are connected by a disulfide bond. Most of the secondary structure elements present in human isozyme II are retained in N. gonorrhoeae carbonic anhydrase, but there are also differences, particularly in the few helical regions. Long deletions in the bacterial enzyme relative to human isozyme II have resulted in a considerable shortening of three surface loops. One of these deletions, corresponding to residues 128 to 139 in the human enzyme, leads to a widening of the entrance to the hydrophobic part of the active site cavity. Practically all the amino acid residues in the active site of human isozyme II are conserved in the N. gonorrhoeae enzyme and have similar structural positions. However, the imidazole ring of a histidine residue, which has been shown to function as a proton shuttle in the catalytic mechanism of the human enzyme, interacts with an extraneous entity, which has tentatively been identified as a 2-mercaptoethanol molecule from the crystallization medium. When this entity is removed by soaking the crystal in a different medium, the side-chain of His66 becomes quite mobile. The structure of a complex with the sulfonamide inhibitor, acetazolamide, has also been determined. Its position in the active site is very similar to that observed in human carbonic anhydrase II.

Acetazolamide↗
PubMed2003

Acetazolamide vasoreactivity evaluated by transcranial harmonic perfusion imaging: relationship with transcranial Doppler sonography and dynamic CT.

UNLABELLED: To establish the reliability and clinical significance of transcranial ultrasonic harmonic perfusion imaging (HPI), we evaluated HPI's relationships with transcranial Doppler (TCD) and with dynamic CT (DCT), during acetazolamide (ACZ) vasoreactivity tests. METHODS: The subjects were 12 neurological patients. Time-averaged maximum velocity (TAVMX) in the middle (MCA) and posterior cerebral arteries was measured by TCD. Time-intensity (-density) curves of HPI (DCT) after bolus intravenous contrast injections were created in 3 regions of interest (ROI) on the axial plane involving the temporal lobe, basal ganglia, and thalamus on both sides. Assessments of vasoreactivity were based on comparisons conducted before and after ACZ administration in terms of: a) relative changes (%delta) of the TCD TAVMX, b) HPI contrast area enlargement, c) %delta of calculated cerebral blood volume and flow of the HPI and DCT. RESULTS: 1) TCD vasoreactivity decrease in the left MCA tended to correlate with lower frequency of HPI contrast area enlargement on the left side. 2) HPI and DCT vasoreactivity tended to be disturbed in the same side ROIs. CONCLUSIONS: Transcranial HPI achieves repeatable non-invasive bedside evaluation of cerebrovascular reserve capacity through qualitative and quantitative measurements of brain tissue perfusion, and will have clinical value in pathophysiological follow-up and therapeutic effectiveness determination of neurointensive care patients.

Acetazolamide↗
PubMed2003

Acetazolamide vasoreactivity in persistent vegetative state and vascular dementia evaluated by transcranial harmonic perfusion imaging and Doppler sonography.

UNLABELLED: To clarify the pathophysiological differences of the cerebrovascular reserve capacity in relation to cerebral cognitive impairments between persistent vegetative state (PVS) and vascular dementia (VD), we evaluated acetazolamide (ACZ) vasoreactivity testing by transcranial harmonic perfusion imaging (HPI) and Doppler sonography (TCD). METHODS: The subjects were 11 adult patients with severe cognitive impairments (4 PVS, 7 VD). TCD mean velocity (Vm) in the middle and posterior cerebral artery (MCA, PCA) and peak intensity (PI), area under curve (AUC), and mean transit time (MTT) analyzed by HPI time-intensity curves in the bilateral temporal lobe (TL), basal ganglia (BG), and thalamus (Th) were evaluated before and after ACZ administration. Resting values and relative changes (%delta) of TCD and HPI parameters were compared between PVS and VD. RESULTS: a) Resting values: There were no significant differences between the two groups. b) Vasoreactivity: 1) PVS: %delta Vm decreased in the left PCA and MCA. %delta PI/AUC/MTT decreased in the left TL and bilateral BG. 2) VD: %delta PI/AUC decreased in the right TL. %delta MTT tended to decrease in the right side. CONCLUSION: ACZ vasoreactivity tests by transcranial HPI and TCD allowed bedside, non-invasive, quantitative evaluation of the pathophysiology of cognitive function impairment and treatments, in relation to cerebrovascular reserve capacity in PVS and VD.

Acetazolamide↗
PubMed1986

Potentiation of antitumor activity of 1-phthalidyl 5-fluorouracil by acetazolamide.

The effect of acetazolamide (A.A.) on the antineoplastic activity of 1-phthalidyl 5-fluorouracil (PH-FU) against rat and mouse solid tumors was examined. A.A., an inhibitor of liver PH-FU hydrolase, had no antitumor activity but greatly enhanced the activity of PH-FU when coadministered. The potentiation was evaluated in terms of suppression of tumor growth and prolongation of the life-span of tumor-bearing animals. Studies also revealed that A.A. elevated the concentration of PH-FU in tumor tissues, where 5-fluorouracil is slowly liberated from PH-FU. The results are consistent with the hypothesis that A.A. prevents enzymic degradation of PH-FU in the liver and promotes its distribution into target organs.

Acetazolamide↗