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The Cochrane Database of Systematic... Jan 2008Primary periodic paralyses are rare inherited muscle diseases characterised by episodes of flaccid weakness affecting one or more limbs, lasting several hours to several... (Review)
Review
BACKGROUND
Primary periodic paralyses are rare inherited muscle diseases characterised by episodes of flaccid weakness affecting one or more limbs, lasting several hours to several days, caused by mutations in skeletal muscle channel genes.
OBJECTIVES
The objective of this review was to systematically review treatment of periodic paralyses.
SEARCH STRATEGY
We searched the Cochrane Neuromuscular Disease Group Trials Register, MEDLINE (from January 1966 to July 2007), and EMBASE (from January 1980 to July 2007) and any other available international medical library sources from the University of Milan for randomised trials.
SELECTION CRITERIA
We included randomised (including cross-over studies) and quasi-randomised trials in participants with primary periodic paralyses, in which any form of treatment, including physical therapy and alternative therapies, was compared to placebo or another treatment.
DATA COLLECTION AND ANALYSIS
Our primary outcome measure was the change in attack severity or frequency by eight weeks from the start of treatment. Our secondary outcome measures were: change in muscle strength and mass; change in Quality of Life, using Short Form 36 (SF36) or similar; preference of treatment strategy; adverse effects at eight weeks.
MAIN RESULTS
Three studies met our inclusion criteria. In one study dichlorphenamide (DCP) vs placebo was tested in two groups of participants: 42 with hypokalemic periodic paralysis (HypoPP) and 31 with hyperkalemic periodic paralysis (HyperPP), based on clinical criteria. Thirty-four of 42 participants with hypokalemic periodic paralysis completed both treatment phases. For the 34 participants having attack rate data for both treatment phases, the mean improvement in attack rate (P = 0.02) and severity-weighted attack rate (P = 0.01) on DCP relative to placebo were statistically significant. Fifteen preferred DCP, three placebo and six their baseline medication. Twenty-four of 31 participants with hyperkalemic periodic paralysis completed both treatment phases: for the 16 participants who had attack rate data for both treatment phases, the mean improvement in attack rate (P = 0.006) and in severity-weighted attack rate (P = 0.02) on DCP relative to placebo were significant. Fifteen preferred DCP, one placebo and five their baseline medication. Acetazolamide proved to improve muscle strength in eight participants with HypoPP in one other study and pinacidil, a potassium channel opener, also improved muscle strength in 2/4 participants with HypoPP in a third study.
AUTHORS' CONCLUSIONS
The largest included study that met our inclusion criteria suggested that DCP was effective in the prevention of episodic weakness in both hypokalemic and hyperkalemic periodic paralyses. The other two studies provide some evidence that either acetazolamide or pinacidil may improve muscle strength. However we still lack sufficient evidence to provide full guidelines for the treatment of people with periodic paralysis.
Topics: Acetazolamide; Carbonic Anhydrase Inhibitors; Dichlorphenamide; Humans; Hypokalemic Periodic Paralysis; Paralysis, Hyperkalemic Periodic; Pinacidil; Randomized Controlled Trials as Topic
PubMed: 18254068
DOI: 10.1002/14651858.CD005045.pub2 -
Bioorganic & Medicinal Chemistry Dec 2010Chitin is an essential structural component of the fungal cell wall. Chitinases are thought to be important for fungal cell wall remodelling, and inhibition of these...
Chitin is an essential structural component of the fungal cell wall. Chitinases are thought to be important for fungal cell wall remodelling, and inhibition of these enzymes has been proposed as a potential strategy for development of novel anti-fungals. The fungal pathogen Aspergillus fumigatus possesses two distinct multi-gene chitinase families. Here we explore acetazolamide as a chemical scaffold for the inhibition of an A. fumigatus 'plant-type' chitinase. A co-crystal structure of AfChiA1 with acetazolamide was used to guide synthesis and screening of acetazolamide analogues that yielded SAR in agreement with these structural data. Although acetazolamide and its analogues are weak inhibitors of the enzyme, they have a high ligand efficiency and as such are interesting leads for future inhibitor development.
Topics: Acetazolamide; Amino Acid Sequence; Antifungal Agents; Aspergillus fumigatus; Binding Sites; Chitinases; Crystallography, X-Ray; Enzyme Inhibitors; Fungal Proteins; Molecular Sequence Data; Sequence Alignment; Structure-Activity Relationship
PubMed: 21044846
DOI: 10.1016/j.bmc.2010.09.062 -
BMJ (Clinical Research Ed.) Oct 2012To assess the efficacy of three different daily doses of acetazolamide in the prevention of acute mountain sickness and to determine the lowest effective dose. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To assess the efficacy of three different daily doses of acetazolamide in the prevention of acute mountain sickness and to determine the lowest effective dose.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
Medline and Embase along with a hand search of selected bibliographies. No language restrictions were applied.
STUDY SELECTION
Randomised controlled trials assessing the use of acetazolamide at 250 mg, 500 mg, or 750 mg daily versus placebo in adults as a drug intervention for the prophylaxis of acute mountain sickness. Included studies were required to state the administered dose of acetazolamide and to randomise participants before ascent to either acetazolamide or placebo. Two reviewers independently carried out the selection process.
DATA EXTRACTION
Two reviewers extracted data concerning study methods, pharmacological intervention with acetazolamide, method of assessment of acute mountain sickness, and event rates in both control and intervention groups, which were verified and analysed by the review team collaboratively.
DATA SYNTHESIS
11 studies (with 12 interventions arms) were included in the review. Acetazolamide at doses of 250 mg, 500 mg, and 750 mg were all effective in preventing acute mountain sickness above 3000 m, with a combined odds ratio of 0.36 (95% confidence interval 0.28 to 0.46). At a dose of 250 mg daily the number needed to treat for acetazolamide to prevent acute mountain sickness was 6 (95% confidence interval 5 to 11). Heterogeneity ranged from I(2)=0% (500 mg subgroup) to I(2)=44% (750 mg subgroup).
CONCLUSIONS
Acetazolamide in doses of 250 mg, 500 mg, and 750 mg daily are all more effective than placebo for preventing acute mountain sickness. Acetazolamide 250 mg daily is the lowest effective dose to prevent acute mountain sickness for which evidence is available.
Topics: Acetazolamide; Acute Disease; Altitude Sickness; Bias; Carbonic Anhydrase Inhibitors; Databases, Bibliographic; Humans; Mountaineering; Outcome Assessment, Health Care; Placebos; Randomized Controlled Trials as Topic; Severity of Illness Index
PubMed: 23081689
DOI: 10.1136/bmj.e6779 -
The British Journal of Ophthalmology Jan 1962
Topics: Acetazolamide; Adult; Ciliary Body; Eye Enucleation; Glaucoma; Humans; Male; Neuroectodermal Tumors, Primitive; Uveal Neoplasms
PubMed: 18170756
DOI: 10.1136/bjo.46.1.58 -
BMJ Case Reports Jan 2016Transient headache and neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL syndrome) consists of recurrent headaches with focal neurological signs, which... (Review)
Review
Transient headache and neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL syndrome) consists of recurrent headaches with focal neurological signs, which can include motor, sensory and aphasic symptoms. Although considered rare, it is becoming increasingly recognised in clinical practice due to the accumulation of case reports. The pathophysiology remains unclear although changes in the neurovascular resemble those found in migraine, which are thought to be triggered by an infectious process. HaNDL can mimic various serious, including life-threatening, diseases, such as stroke and meningoencephalitis, which is why vigorous tests should be sought before this diagnosis of exclusion can be reached. Treatment is symptomatic and the prognosis is excellent. A literature review of the topic is discussed. We report an adolescent girl who presented with recurrent expressive dysphasia and right-sided hypoaesthesia and moderate occipital headaches who was diagnosed with HaNDL syndrome.
Topics: Acetazolamide; Adolescent; Aphasia, Broca; Carbonic Anhydrase Inhibitors; Diagnosis, Differential; Female; Headache; Humans; Hypesthesia; Lymphocytosis; Nervous System Diseases; Syndrome
PubMed: 26768705
DOI: 10.1136/bcr-2015-213018 -
Experimental Physiology May 2024It has been proposed that diuretics can improve renal tissue oxygenation through inhibition of tubular sodium reabsorption and reduced metabolic demand. However, the...
It has been proposed that diuretics can improve renal tissue oxygenation through inhibition of tubular sodium reabsorption and reduced metabolic demand. However, the impact of clinically used diuretic drugs on the renal cortical and medullary microcirculation is unclear. Therefore, we examined the effects of three commonly used diuretics, at clinically relevant doses, on renal cortical and medullary perfusion and oxygenation in non-anaesthetised healthy sheep. Merino ewes received acetazolamide (250 mg; n = 9), furosemide (20 mg; n = 10) or amiloride (10 mg; n = 7) intravenously. Systemic and renal haemodynamics, renal cortical and medullary tissue perfusion and , and renal function were then monitored for up to 8 h post-treatment. The peak diuretic response occurred 2 h (99.4 ± 14.8 mL/h) after acetazolamide, at which stage cortical and medullary tissue perfusion and were not significantly different from their baseline levels. The peak diuretic response to furosemide occurred at 1 h (196.5 ± 12.3 mL/h) post-treatment but there were no significant changes in cortical and medullary tissue oxygenation during this period. However, cortical tissue fell from 40.1 ± 3.8 mmHg at baseline to 17.2 ± 4.4 mmHg at 3 h and to 20.5 ± 5.3 mmHg at 6 h after furosemide administration. Amiloride did not produce a diuretic response and was not associated with significant changes in cortical or medullary tissue oxygenation. In conclusion, clinically relevant doses of diuretic agents did not improve regional renal tissue oxygenation in healthy animals during the 8 h experimentation period. On the contrary, rebound renal cortical hypoxia may develop after dissipation of furosemide-induced diuresis.
Topics: Animals; Furosemide; Acetazolamide; Amiloride; Diuretics; Sheep; Female; Kidney Cortex; Kidney Medulla; Oxygen; Hemodynamics; Oxygen Consumption
PubMed: 38551893
DOI: 10.1113/EP091479 -
Journal of Cerebral Blood Flow and... Mar 2017A quantitative estimate of cerebral blood oxygen saturation is of critical importance in the investigation of cerebrovascular disease. We aimed to measure the change in...
A quantitative estimate of cerebral blood oxygen saturation is of critical importance in the investigation of cerebrovascular disease. We aimed to measure the change in venous oxygen saturation (Y) before and after the intake of the vaso-dynamic agents caffeine and acetazolamide with high spatial resolution using susceptibility mapping. Caffeine and acetazolamide were administered on separate days to five healthy volunteers to measure the change in oxygen extraction fraction. The internal streaking artifacts in the susceptibility maps were reduced by giving an initial susceptibility value uniformly to the structure-of-interest, based on a priori information. Using this technique, Y for normal physiological conditions, post-caffeine and post-acetazolamide was measured inside the internal cerebral veins as Y = 69.1 ± 3.3%, Y = 60.5 ± 2.8%, and Y = 79.1 ± 4.0%. This suggests that susceptibility mapping can serve as a sensitive biomarker for measuring reductions in cerebro-vascular reserve through abnormal vascular response. The percentage change in oxygen extraction fraction for caffeine and acetazolamide were found to be +27.0 ± 3.8% and -32.6 ± 2.1%, respectively. Similarly, the relative changes in cerebral blood flow in the presence of caffeine and acetazolamide were found to be -30.3% and + 31.5%, suggesting that the cerebral metabolic rate of oxygen remains stable between normal and challenged brain states for healthy subjects.
Topics: Acetazolamide; Adult; Caffeine; Cerebral Veins; Cerebrovascular Circulation; Healthy Volunteers; Humans; Magnetic Resonance Imaging; Oxygen Consumption
PubMed: 27029391
DOI: 10.1177/0271678X16641129 -
The Cochrane Database of Systematic... 2001Carbonic anhydrase inhibitors such as acetazolamide cause a mild metabolic acidosis and may stimulate breathing. Some patients with severe chronic obstructive pulmonary... (Review)
Review
BACKGROUND
Carbonic anhydrase inhibitors such as acetazolamide cause a mild metabolic acidosis and may stimulate breathing. Some patients with severe chronic obstructive pulmonary disease (COPD) develop chronic hypercapnic ventilatory failure. In theory, they may benefit from use of these drugs with a fall in arterial carbon dioxide level (PCO2) and a rise in arterial oxygen (PO2).
OBJECTIVES
To determine the effectiveness and safety of acetazolamide in the treatment of hypercapnic ventilatory failure due to COPD SEARCH STRATEGY: The Cochrane Register of Controlled Clinical Trials was searched along with Medline, Embase, Central and CINAHL for relevant randomised control trials.
SELECTION CRITERIA
Trials were included in the review provided they were placebo controlled, carried out in patients with stable chronic ventilatory failure due to COPD.
DATA COLLECTION AND ANALYSIS
Data were extracted and analysed by two reviewers (PJ and MG) and agreement was reached by consensus. Where data could be aggregated they were analysed using a fixed efefcts model and reported as a weighted mean difference (WMD) and its associated 95% confidence interval (95% CI).
MAIN RESULTS
Four trials were included in the review. Of these, two were randomised parallel studies, one was a crossover study and the other had a sequential design. A total of 84 patients were involved. Study quality was mixed and the studies were short (typically two weeks). All studies showed a similar direction and size of effect. In the randomised parallel studies, acetazolamide caused a metabolic acidosis and produced a non-significant fall in PCO2 (WMD -0.41 kPa; 95% CI -0.91, 0.09; N=2) and a significant rise in PO2 (WMD 1.54 kPa; 95% CI 0.97, 2.11; N=2). One study reported an improvement in sleep but there were no data concerning outcomes such as health status, symptoms, exacerbation rate, hospital admissions or deaths. Side effects were reported infrequently.
REVIEWER'S CONCLUSIONS
Acetazolamide can produce a small increase in arterial PO2 and fall in PCO2. These conclusions are drawn from a few small short studies that were not all of high quality. It is not known whether this physiological improvement is associated with clinical benefit.
Topics: Acetazolamide; Carbonic Anhydrase Inhibitors; Clinical Trials as Topic; Female; Humans; Hypercapnia; Male; Pulmonary Disease, Chronic Obstructive; Respiratory Insufficiency
PubMed: 11279770
DOI: 10.1002/14651858.CD002881 -
The Cochrane Database of Systematic... Jun 2017High altitude illness (HAI) is a term used to describe a group of cerebral and pulmonary syndromes that can occur during travel to elevations above 2500 metres (8202... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
High altitude illness (HAI) is a term used to describe a group of cerebral and pulmonary syndromes that can occur during travel to elevations above 2500 metres (8202 feet). Acute hypoxia, acute mountain sickness (AMS), high altitude cerebral oedema (HACE) and high altitude pulmonary oedema (HAPE) are reported as potential medical problems associated with high altitude. In this review, the first in a series of three about preventive strategies for HAI, we assess the effectiveness of six of the most recommended classes of pharmacological interventions.
OBJECTIVES
To assess the clinical effectiveness and adverse events of commonly-used pharmacological interventions for preventing acute HAI.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (OVID), Embase (OVID), LILACS and trial registries in January 2017. We adapted the MEDLINE strategy for searching the other databases. We used a combination of thesaurus-based and free-text terms to search.
SELECTION CRITERIA
We included randomized-controlled and cross-over trials conducted in any setting where commonly-used classes of drugs were used to prevent acute HAI.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures as expected by Cochrane.
MAIN RESULTS
We included 64 studies (78 references) and 4547 participants in this review, and classified 12 additional studies as ongoing. A further 12 studies await classification, as we were unable to obtain the full texts. Most of the studies were conducted in high altitude mountain areas, while the rest used low pressure (hypobaric) chambers to simulate altitude exposure. Twenty-four trials provided the intervention between three and five days prior to the ascent, and 23 trials, between one and two days beforehand. Most of the included studies reached a final altitude of between 4001 and 5000 metres above sea level. Risks of bias were unclear for several domains, and a considerable number of studies did not report adverse events of the evaluated interventions. We found 26 comparisons, 15 of them comparing commonly-used drugs versus placebo. We report results for the three most important comparisons: Acetazolamide versus placebo (28 parallel studies; 2345 participants)The risk of AMS was reduced with acetazolamide (risk ratio (RR) 0.47, 95% confidence interval (CI) 0.39 to 0.56; I = 0%; 16 studies; 2301 participants; moderate quality of evidence). No events of HAPE were reported and only one event of HACE (RR 0.32, 95% CI 0.01 to 7.48; 6 parallel studies; 1126 participants; moderate quality of evidence). Few studies reported side effects for this comparison, and they showed an increase in the risk of paraesthesia with the intake of acetazolamide (RR 5.53, 95% CI 2.81 to 10.88, I = 60%; 5 studies, 789 participants; low quality of evidence). Budenoside versus placebo (2 parallel studies; 132 participants)Data on budenoside showed a reduction in the incidence of AMS compared with placebo (RR 0.37, 95% CI 0.23 to 0.61; I = 0%; 2 studies, 132 participants; low quality of evidence). Studies included did not report events of HAPE or HACE, and they did not find side effects (low quality of evidence). Dexamethasone versus placebo (7 parallel studies; 205 participants)For dexamethasone, the data did not show benefits at any dosage (RR 0.60, 95% CI 0.36 to 1.00; I2 = 39%; 4 trials, 176 participants; low quality of evidence). Included studies did not report events of HAPE or HACE, and we rated the evidence about adverse events as of very low quality.
AUTHORS' CONCLUSIONS
Our assessment of the most commonly-used pharmacological interventions suggests that acetazolamide is an effective pharmacological agent to prevent acute HAI in dosages of 250 to 750 mg/day. This information is based on evidence of moderate quality. Acetazolamide is associated with an increased risk of paraesthesia, although there are few reports about other adverse events from the available evidence. The clinical benefits and harms of other pharmacological interventions such as ibuprofen, budenoside and dexamethasone are unclear. Large multicentre studies are needed for most of the pharmacological agents evaluated in this review, to evaluate their effectiveness and safety.
Topics: Acetazolamide; Adolescent; Adult; Aged; Altitude Sickness; Brain Edema; Budesonide; Carbonic Anhydrase Inhibitors; Dexamethasone; Glucocorticoids; Humans; Hypertension, Pulmonary; Middle Aged; Paresthesia; Publication Bias; Randomized Controlled Trials as Topic
PubMed: 28653390
DOI: 10.1002/14651858.CD009761.pub2 -
PloS One 2020The alternative mechanical theory of glaucoma, in which an increased pressure difference across the lamina cribrosa (difference between intraocular and intracranial...
The alternative mechanical theory of glaucoma, in which an increased pressure difference across the lamina cribrosa (difference between intraocular and intracranial pressure; IOP and ICP), rather than solely an elevated IOP, leads to structural and functional vision loss, is still controversial. If the theory is true, a drug that simultaneously lowers both the IOP and ICP may be ineffective. The aim of this study was to determine how acetazolamide (AAZ; a drug prescribed in glaucoma that aims to lower the IOP) affects both IOP and ICP in glaucoma patients and to compare the magnitude and time course of the induced pressure changes with those of healthy subjects not taking AAZ. IOP and noninvasive ICP (measured through emissions from the ear) were measured in 20 glaucoma patients taking 125 mg of AAZ twice daily. Measurements were taken for 30 minutes before taking the drug and for 2 hours post-ingestion. Comparisons were made with 13 age-similar controls. After 12 hours with no anti-glaucoma medication, AAZ did not further reduce IOP in glaucoma patients compared to controls (P = 0.58) but did reduce ICP compared to controls (P = 0.035), by approximately 4 mmHg. Our findings suggest that there are periods during the day when the pressure difference across the lamina cribrosa is larger in case of AAZ use. Future studies should focus on improving the noninvasive ICP testing, different doses and dosing schedules of AAZ, and the time course of IOP in glaucoma patients not taking AAZ.
Topics: Acetazolamide; Aged; Carbonic Anhydrase Inhibitors; Female; Glaucoma; Humans; Intracranial Pressure; Intraocular Pressure; Male; Middle Aged
PubMed: 32555666
DOI: 10.1371/journal.pone.0234690