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Journal of Clinical Medicine Jan 2024Heart failure (HF) patients often experience persistent fluid overload despite standard diuretic therapy. The adjunctive use of acetazolamide, a carbonic anhydrase... (Review)
Review
Heart failure (HF) patients often experience persistent fluid overload despite standard diuretic therapy. The adjunctive use of acetazolamide, a carbonic anhydrase inhibitor, in combination with loop diuretics has shown promise in improving decongestion and diuretic efficacy. This literature review aims to analyze six studies evaluating the effectiveness of acetazolamide as an additive treatment for acute decompensated heart failure (ADHF) and its impact on various outcomes. We searched the PubMed database using the terms "acetazolamide heart failure". We refined our search with specific filters (as shown our PRISMA flow diagram) and exclusion criteria, narrowing down our results to five studies. We included an extra study via expert recommendation, ultimately including six studies for comprehensive analysis. The review highlights the positive effects of acetazolamide on decongestion, natriuresis, and diuresis in HF patients. However, it also showcases the limitations of these trials. While the reviewed studies demonstrate the potential benefits of acetazolamide in enhancing decongestion and diuretic efficiency, there are limitations to consider, including small sample sizes, lack of blinding, and limited external validity. Further research is needed to confirm these findings, compare acetazolamide with other diuretic combinations, and explore its effects in a broader population of heart failure patients, including those in the United States. The use of acetazolamide in HF management warrants continued investigation to optimize its role in improving decongestion and patient outcomes.
PubMed: 38202295
DOI: 10.3390/jcm13010288 -
The Journal of Headache and Pain Jul 2023In idiopathic intracranial hypertension (IIH), sustained weight loss is the main pillar in modifying disease course, whereby glucagon-like peptide-1 receptor agonists...
BACKGROUND
In idiopathic intracranial hypertension (IIH), sustained weight loss is the main pillar in modifying disease course, whereby glucagon-like peptide-1 receptor agonists (GLP-1-RAs) could present an attractive treatment option.
METHODS
In this open-label, single-center, case-control pilot study, patients with IIH (pwIIH) and a body mass index (BMI) of ≥ 30 kg/m were offered to receive a GLP-1-RA (semaglutide, liraglutide) in addition to the usual care weight management (UCWM). Patients electing for UCWM only served as a control group matched for age-, sex- and BMI (1:2 ratio). The primary endpoint was the percentage weight loss at six months (M6) compared to baseline. Secondary endpoints included the rate of patients with a weight loss of ≥ 10%, monthly headache days (MHD), the rate of patients with a ≥ 30% and ≥ 50% reduction in MHD, visual outcome parameters, and adverse events (AEs).
RESULTS
We included 39 pwIIH (mean age 33.6 years [SD 8.0], 92.3% female, median BMI 36.3 kg/m [IQR 31.4-38.3]), with 13 patients being treated with GLP-1-RAs. At M6, mean weight loss was significantly higher in the GLP-1-RA group (-12.0% [3.3] vs. -2.8% [4.7]; p < 0.001). Accordingly, weight loss of ≥ 10% was more common in this group (69.2% vs. 4.0%; p < 0.001). Median reduction in MHD was significantly higher in the GLP-1-RA group (-4 [-10.5, 0.5] vs. 0 [-3, 1]; p = 0.02), and the 50% responder rate was 76.9% vs. 40.0% (p = 0.04). Visual outcome parameters did not change significantly from baseline to M6. Median reduction in acetazolamide dosage was significantly higher in the GLP-1-RA group (-16.5% [-50, 0] vs. 0% [-25, 50]; p = 0.04). AEs were mild or moderate and attributed to gastrointestinal symptoms in 9/13 patients. None of the AEs led to premature treatment discontinuation.
CONCLUSIONS
This open-label, single-center pilot study suggests that GLP-1-RAs are an effective and safe treatment option for achieving significant weight loss with a favorable effect on headache, leading to reduced acetazolamide dosage in pwIIH.
Topics: Humans; Female; Adult; Male; Pseudotumor Cerebri; Glucagon-Like Peptide-1 Receptor; Acetazolamide; Pilot Projects; Glucagon-Like Peptide 1; Headache; Weight Loss
PubMed: 37460968
DOI: 10.1186/s10194-023-01631-z -
Acute Myopic Shift after a Single Dose of Acetazolamide: A Case Report and Review of the Literature.Klinische Monatsblatter Fur... Apr 2024We report the case of a 32-year-old male who presented with an acute myopic shift as a result of uveal effusion following a single administration of 250 mg... (Review)
Review
We report the case of a 32-year-old male who presented with an acute myopic shift as a result of uveal effusion following a single administration of 250 mg acetazolamide. The drug was discontinued and following cycloplegia and topical steroid therapy, we observed progressive deepening of the anterior chamber, reopening of the iridocorneal angle, and complete resolution of the myopic shift after 5 days. A literature review since 1956 identified 23 cases, including ours, which developed a myopic shift after a median time of 24 h (3 - 24) following a median dose of 500 mg (125 - 1000) acetazolamide, with about a third complicated by angle closure ocular hypertension. This presumed idiosyncratic reaction can occur without prior drug exposure and independent of the phakic status. Treatment options include systematic drug withdrawal associated with cycloplegia, anti-glaucomatous agents, and/or corticosteroids. Full recovery is achieved within about 5 days (2 - 14). Given the widespread use of acetazolamide, awareness of this idiosyncratic reaction is crucial to avoid complications of acute angle-closure glaucoma.
Topics: Humans; Acetazolamide; Male; Adult; Myopia; Carbonic Anhydrase Inhibitors; Acute Disease; Treatment Outcome
PubMed: 38653306
DOI: 10.1055/a-2244-6160 -
Frontiers in Pharmacology 2023The increase of intracellular Ca concentration, produced principally by its influx through the L-type Ca channels, is one of the major contributors to the... (Review)
Review
The increase of intracellular Ca concentration, produced principally by its influx through the L-type Ca channels, is one of the major contributors to the ischemia-reperfusion injury. The inhibition of those channels in different experimental models was effective to ameliorate the post-ischemic damage. However, at a clinical level, the results were contradictory. Recent results of our group obtained in an ¨¨ heart model demonstrated that a chemical derived from acetazolamide, the N-methylacetazolamide (NMA) protected the heart against ischemia-reperfusion injury, diminishing the infarct size and improving the post-ischemic recovery of myocardial function and mitochondrial dynamic. A significant inhibitory action on L-type Ca channels was also detected after NMA treatment, suggesting this action as responsible for the beneficial effects on myocardium exerted by this compound. Although these results were promising, the effectiveness of NMA in the treatment of ischemic heart disease in humans as well as the advantages or disadvantages in comparison to the classic calcium antagonists needs to be investigated.
PubMed: 37637427
DOI: 10.3389/fphar.2023.1223132 -
Brain Sciences Dec 2023Acetazolamide is a non-competitive inhibitor of carbonic anhydrase, an enzyme expressed in different cells of the central nervous system (CNS) and involved in the... (Review)
Review
BACKGROUND
Acetazolamide is a non-competitive inhibitor of carbonic anhydrase, an enzyme expressed in different cells of the central nervous system (CNS) and involved in the regulation of cerebral blood flow (CBF). The aim of this review was to understand the effects of acetazolamide on CBF, intracranial pressure (ICP) and brain tissue oxygenation (PbtO) after an acute brain injury (ABI).
METHODS
Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA), we performed a comprehensive, computer-based, literature research on the PubMed platform to identify studies that have reported the effects on CBF, ICP, or PbtO of acetazolamide administered either for therapeutic or diagnostic purposes in patients with subarachnoid hemorrhage, intracerebral hemorrhage, traumatic brain injury, and hypoxic-ischemic encephalopathy.
RESULTS
From the initial search, 3430 records were identified and, through data selection, 11 of them were included for the qualitative analysis. No data on the effect of acetazolamide on ICP or PbtO were found. Cerebral vasomotor reactivity (VMR-i.e., the changing in vascular tone due to a vasoactive substance) to acetazolamide tends to change during the evolution of ABI, with the nadir occurring during the subacute stage. Moreover, VMR reduction was correlated with clinical outcome.
CONCLUSIONS
This systematic review showed that the available studies on the effects of acetazolamide on brain hemodynamics in patients with ABI are scarce. Further research is required to better understand the potential role of this drug in ABI patients.
PubMed: 38137126
DOI: 10.3390/brainsci13121678 -
Frontiers in Neurology 2023Cerebral hemodynamics in moyamoya disease (MMD) is complex and needs further elucidation. The primary aim of the study was to determine the association of the...
BACKGROUND
Cerebral hemodynamics in moyamoya disease (MMD) is complex and needs further elucidation. The primary aim of the study was to determine the association of the cerebrovascular reserve (CVR) with cerebral blood flow (CBF) disturbances, oxygen extraction fraction (OEF), and energy metabolism () in MMD, using arterial spin label magnetic resonance imaging (ASL-MRI) before and after acetazolamide administration.
METHODS
Thirty-nine ASL-MRI scans with a concurrent acetazolamide challenge from 16 MMD patients at the Uppsala University Hospital, Sweden, 2016-2021, were retrospectively analyzed. CBF was assessed before and 5, 15, and 25 min after acetazolamide administration, and the maximal response CVR was used for further analyses. Dynamic susceptibility contrast (DSC) MRI was performed 30 min after acetazolamide injection, and the data were analyzed using the Cercare Medical Neurosuite to assess capillary transit time heterogeneity (CTTH; indicating microvascular function), OEF, and .
RESULTS
In the ACA territory, a lower CVR was associated with lower baseline CBF, higher CTTH, and higher OEF but not with in generalized estimating equation models. In the MCA territory, lower CVR was associated with lower baseline CBF and higher but not with CTTH and OEF.
CONCLUSION
Altogether, a compromised CVR in MMD patients reflected disturbances in macro-/microvascular blood flow, oxygenation, and CMRO. ASL-MRI with acetazolamide challenge is a feasible and radiation-free alternative to positron emission tomography (PET) imaging in MMD.
PubMed: 37545732
DOI: 10.3389/fneur.2023.1190309 -
Neurology. Genetics Feb 2024Paroxysmal ataxia is typically characterized by early-onset attacks of cerebellar ataxia. Late-onset cerebellar ataxia (LOCA) comprises a group of neurodegenerative...
OBJECTIVES
Paroxysmal ataxia is typically characterized by early-onset attacks of cerebellar ataxia. Late-onset cerebellar ataxia (LOCA) comprises a group of neurodegenerative disorders mainly characterized by adult-onset progressive cerebellar ataxia. A deep intronic expansion of a GAA triplet in the gene encoding fibroblast growth factor 14 has recently been identified as a frequent cause of LOCA.
METHODS
We describe a patient with paroxysmal ataxia/dysarthria due to a repeat expansion and 3 affected family members.
RESULTS
The 4 patients had paroxysmal ataxia/dysarthria occurring between 45 and 50 years as the initial manifestation of a repeat expansion. The index case was investigated in detail. We have provided a video showing one of her paroxysmal episodes that could be triggered by alcohol, coffee, exertion, emotion, or cigarette smoking. Brain MRI revealed mild cerebellar atrophy, and oculography showed a subclinical downbeat nystagmus. Treatment with acetazolamide resulted in remarkable improvement.
DISCUSSION
Paroxysmal dysarthria/ataxia should prompt the clinician to test for repeat expansion/SCA27B, especially when the paroxysmal attacks are associated with late-onset cerebellar ataxia and/or a family history consistent with a dominant disorder.
PubMed: 38170134
DOI: 10.1212/NXG.0000000000200118 -
Hellenic Journal of Cardiology : HJC =... 2023The treatment of congestion in heart failure (HF) is a challenge despite the therapeutic arsenal available. The aim of this study was to analyze different combinations...
BACKGROUND
The treatment of congestion in heart failure (HF) is a challenge despite the therapeutic arsenal available. The aim of this study was to analyze different combinations of diuretics used to resolve congestion in patients admitted for decompensated HF and to define clinical profiles according to these treatments.
METHODS
Single-center study of 1,559 patients admitted for decompensated HF was done between 2016 and 2020. Patients were grouped according to the diuretic combination that led to clinical stabilization and discharge from the hospital: (1) Loop diuretic. (2) Loop diuretic + distal tubule (antialdosterone ± thiazides). (3) Loop diuretic + distal + proximal tubule (acetazolamide ± SGLT2 inhibitor). (4) Loop diuretic + distal tubule + collecting duct (tolvaptan). (5) Loop diuretic + distal + proximal + collecting duct. Based on these diuretic combinations, profiles with clinical, analytical, and echocardiographic differences were established.
RESULTS
There were more previous hospitalizations in groups 4 and 5 (p = 0.001) with a predominance of pulmonary congestion in profiles 1 and 2 and systemic congestion in 3, 4, and 5. Creatinine and CA125 were higher in profiles 4 and 5 (p = 0.01 and p = 0.0001), with no differences in NT-proBNP. Profiles 4 and 5 had a higher proportion of dilatation and depression of right ventricular (p = 0.0001) and left ventricular (p = 0.003) function. Diuretic therapy-defined groups showed difference in clinical characteristics.
CONCLUSIONS
The diuretic treatment used identifies five clinical profiles according to the degree of congestion, renal function, CA125, and right ventricular functionality. These profiles would guide the best diuretic treatment on admission.
Topics: Humans; Diuretics; Sodium Potassium Chloride Symporter Inhibitors; Treatment Outcome; Heart Failure; Phenotype
PubMed: 37068639
DOI: 10.1016/j.hjc.2023.03.009 -
Neurology Nov 2023Idiopathic intracranial hypertension (IIH) is associated with obesity; however, there is a lack of clinical consensus on how to manage weight in IIH. The aim of this...
BACKGROUND AND OBJECTIVES
Idiopathic intracranial hypertension (IIH) is associated with obesity; however, there is a lack of clinical consensus on how to manage weight in IIH. The aim of this systematic review was to evaluate weight loss interventions in people with IIH to determine which intervention is superior in terms of weight loss, reduction in intracranial pressure (ICP), benefit to visual and headache outcomes, quality of life, and mental health.
METHODS
A systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered with PROSPERO (CRD42023339569). MEDLINE and CINAHL were searched for relevant literature published from inception until December 15, 2022. Screening and quality appraisal was conducted by 2 independent reviewers. Recommendations were graded using Scottish Intercollegiate Guidelines Network methodology.
RESULTS
A total of 17 studies were included. Bariatric surgery resulted in 27.2-27.8 kg weight loss at 24 months (Level 1- to 1++). Lifestyle weight management interventions resulted in between 1.4 and 15.7 kg weight loss (Level 2+ to 1++). Bariatric surgery resulted in the greatest mean reduction in ICP (-11.9 cm HO) at 24 months (Level 1++), followed by multicomponent lifestyle intervention + acetazolamide (-11.2 cm HO) at 6 months (Level 1+) and then a very low-energy diet intervention (-8.0 cm HO) at 3 months (Level 2++). The least ICP reduction was shown at 24 months after completing a 12-month multicomponent lifestyle intervention (-3.5 cm HO) (Level 1++). Reduction in body weight was shown to be highly correlated with reduction in ICP (Level 2++ to 1++).
DISCUSSION
Bariatric surgery should be considered for women with IIH and a body mass index (BMI) ≥35 kg/m since this had the most robust evidence for sustained weight management (grade A). A multicomponent lifestyle intervention (diet + physical activity + behavior) had the most robust evidence for modest weight loss with a BMI <35 kg/m (grade B). Longer-term outcomes for weight management interventions in people with IIH are required to determine whether there is a superior weight loss intervention for IIH.
Topics: Humans; Adult; Female; Pseudotumor Cerebri; Quality of Life; Obesity; Weight Loss; Bariatric Surgery; Intracranial Hypertension
PubMed: 37813577
DOI: 10.1212/WNL.0000000000207866 -
Journal of Enzyme Inhibition and... Dec 2023A series of phthalimide-capped benzene sulphonamides (-) reported by our group for dengue protease inhibitory activity have been evaluated for their carbonic anhydrase...
A series of phthalimide-capped benzene sulphonamides (-) reported by our group for dengue protease inhibitory activity have been evaluated for their carbonic anhydrase (hCA, EC 4.2.1.1) inhibitory activity against hCA I, hCA II. Compounds , , , and showed hCA I inhibition, whereas , , and showed hCA II inhibition at nanomolar concentrations. Among these compounds, displayed potent inhibitory activity against the hCA I (Ki = 28.5 nM) and hCA II (Ki = 2.2 nM), being 10 and 6 times more potent than acetazolamide, a standard inhibitor (Ki = 250 nM and 12 nM), respectively. Furthermore, this compound displayed 14-fold selectivity towards the hCA II isoform compared to hCA I. Molecular docking and MD simulations were performed to understand the atomic level interactions responsible for the selectivity of compound towards hCA II.
Topics: Molecular Structure; Structure-Activity Relationship; Benzene; Carbonic Anhydrase I; Carbonic Anhydrase II; Molecular Docking Simulation; Benzene Derivatives; Carbonic Anhydrase Inhibitors; Carbonic Anhydrases; Sulfonamides; Phthalimides
PubMed: 37439360
DOI: 10.1080/14756366.2023.2235089