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Cardiology Research Apr 2024Acetazolamide and thiazide diuretics have been combined with loop diuretics to overcome diuretic resistance in heart failure patients. However, recent studies have... (Review)
Review
Acetazolamide and thiazide diuretics have been combined with loop diuretics to overcome diuretic resistance in heart failure patients. However, recent studies have assessed the upfront combination of acetazolamide and hydrochlorothiazide with loop diuretics in hospitalized patients with acute decompensated heart failure without loop diuretic resistance. We reviewed two recent randomized controlled trials on the upfront use of acetazolamide and thiazide diuretics in acute decompensated heart failure, respectively. When the two trials on acetazolamide are considered together, adding oral or intravenous acetazolamide to loop diuretics in decompensated heart failure patients resulted in increased diuresis and natriuresis. However, the effects were significantly higher in patients with serum bicarbonate ≥ 27 mmol/L and those with higher baseline glomerular filtration rate (GFR). Similarly, when the two trials on thiazide diuretics are considered together, adding hydrochlorothiazide to loop diuretics in decompensated heart failure patients resulted in increased diuresis and weight loss. However, it increases the risk of impaired renal function. When all the trials are considered together, the upfront use of acetazolamide may be helpful in carefully selected patients, including patients with underlying elevated bicarbonate levels (≥ 27 mmol/L) and those with good renal function (GFR > 50). Conversely, though the upfront use of thiazide diuretic added to intravenous furosemide improved diuretic response in acute decompensated heart failure, it causes an increased risk of worsening renal function and lack of clear evidence of reducing hospital length of stay.
PubMed: 38645830
DOI: 10.14740/cr1627 -
Circulation Jan 2023Acetazolamide inhibits proximal tubular sodium reabsorption and improved decongestion in the ADVOR (Acetazolamide in Decompensated Heart Failure with Volume Overload)... (Randomized Controlled Trial)
Randomized Controlled Trial
Decongestion With Acetazolamide in Acute Decompensated Heart Failure Across the Spectrum of Left Ventricular Ejection Fraction: A Prespecified Analysis From the ADVOR Trial.
BACKGROUND
Acetazolamide inhibits proximal tubular sodium reabsorption and improved decongestion in the ADVOR (Acetazolamide in Decompensated Heart Failure with Volume Overload) trial. It remains unclear whether the decongestive effects of acetazolamide differ across the spectrum of left ventricular ejection fraction (LVEF).
METHODS
This is a prespecified analysis of the randomized, double-blind, placebo-controlled ADVOR trial that enrolled 519 patients with acute heart failure (HF), clinical signs of volume overload (eg, edema, pleural effusion, or ascites), NTproBNP (N-terminal pro-B-type natriuretic peptide) >1000 ng/L, or BNP (B-type natriuretic peptide) >250 ng/mL to receive intravenous acetazolamide (500 mg once daily) or placebo in addition to standardized intravenous loop diuretics (twice that of the oral home maintenance dose). Randomization was stratified according to LVEF (≤40% or >40%). The primary end point was successful decongestion, defined as the absence of signs of volume overload within 3 days from randomization without the need for mandatory escalation of decongestive therapy because of poor urine output.
RESULTS
Median LVEF was 45% (25th to 75th percentile; 30% to 55%), and 43% had an LVEF ≤40%. Patients with lower LVEF were younger and more likely to be male with a higher prevalence of ischemic heart disease, higher NTproBNP, less atrial fibrillation, and lower estimated glomerular filtration rate. No interaction on the overall beneficial treatment effect of acetazolamide to the primary end point of successful decongestion (OR, 1.77 [95% CI, 1.18-2.63]; =0.005; all values for interaction >0.401) was found when LVEF was assessed per randomization stratum (≤40% or >40%), or as HF with reduced ejection fraction, HF with mildly reduced ejection fraction, and HF with preserved ejection fraction, or on a continuous scale. Acetazolamide resulted in improved diuretic response measured by higher cumulative diuresis and natriuresis and shortened length of stay without treatment effect modification by baseline LVEF (all values for interaction >0.160).
CONCLUSIONS
When added to treatment with loop diuretics in patients with acute decompensated HF, acetazolamide improves the incidence of successful decongestion and diuretic response, and shortens length of stay without treatment effect modification by baseline LVEF.
REGISTRATION
URL: https://www.
CLINICALTRIALS
gov; Unique identifier: NCT03505788.
Topics: Humans; Male; Female; Acetazolamide; Stroke Volume; Natriuretic Peptide, Brain; Ventricular Function, Left; Sodium Potassium Chloride Symporter Inhibitors; Treatment Outcome; Heart Failure; Diuretics; Ventricular Dysfunction, Left
PubMed: 36335479
DOI: 10.1161/CIRCULATIONAHA.122.062486 -
World Neurosurgery Nov 2022Dural venous sinus stenting (VSS) is an effective intervention for patients with idiopathic intracranial hypertension (IIH) refractory to medical treatment. Our goal was...
BACKGROUND
Dural venous sinus stenting (VSS) is an effective intervention for patients with idiopathic intracranial hypertension (IIH) refractory to medical treatment. Our goal was to evaluate the efficacy by utilizing a large multi-institutional sample.
METHODS
Five hundred forty-one patients >18 years old who underwent VSS within 3 years of IIH diagnosis were queried using Current Procedural Terminology and International Classification of Diseases, Tenth Revision codes from the TriNetX Analytics Network. Patient demographics, baseline symptoms, procedures, and clinical outcomes were evaluated within 1 year postoperatively. Outcomes examined were headache, tinnitus, blindness/low vision, optic nerve sheath fenestration (ONSF), cerebrospinal fluid (CSF) shunt, and use of medications (acetazolamide, methazolamide, furosemide, topiramate, tricyclic antidepressants, and valproate) for IIH. Prestent and poststent data were compared using Fisher exact test, and the odds ratios were computed using the Baptista-Pike method.
RESULTS
The mean age at VSS was 36.7 ± 10.6; 92% were female, 65% of patients were Caucasian, 25% were Black/African American, 1% were Asian, and 9% were of other/unknown race. Within the 1-year follow-up, acetazolamide and topiramate use were significantly reduced post-VSS (P < 0.0001∗; odds ratio, 0.45; confidence interval, 0.35-0.57 and P = 0.03∗; odds ratio, 0.71; confidence interval, 0.52-0.95, respectively). Also, headaches, visual disturbance, dizziness/giddiness, and tinnitus significantly improved post-VSS (P < 0.005∗). Finally, the number of CSF shunt procedures and ONSF procedures demonstrated no significant change post-VSS (P > 0.05).
CONCLUSIONS
VSS is an effective and safe procedure resulting in significant improvement of headaches, visual impairment, dizziness, and tinnitus, acetazolamide and topiramate usage were lower after VSS in patients with IIH. The paucity of pre-VSS and post-VSS CSF shunt and ONSF procedure data does not provide enough evidence to establish significance.
Topics: Female; Male; Humans; Pseudotumor Cerebri; Topiramate; Acetazolamide; Tinnitus; Dizziness; Cranial Sinuses; Headache; Stents; Intracranial Hypertension
PubMed: 35973522
DOI: 10.1016/j.wneu.2022.08.035 -
British Journal of Pharmacology Jan 2024Diseases of raised intracranial pressure (ICP) cause severe morbidity and mortality. Multiple drugs are utilised to lower ICP including acetazolamide and topiramate....
BACKGROUND AND PURPOSE
Diseases of raised intracranial pressure (ICP) cause severe morbidity and mortality. Multiple drugs are utilised to lower ICP including acetazolamide and topiramate. However, the evidence for their use is unclear. We aimed to assess the ICP modulatory effects and molecular effects at the choroid plexus (CP) of acetazolamide and topiramate.
EXPERIMENTAL APPROACH
Female rats were implanted with telemetric ICP probes for physiological, freely moving 24/7 ICP recordings. Randomised cross-over studies were performed, where rats received acute (24 h) high doses of acetazolamide and topiramate, and chronic (10 days) clinically equivalent doses of acetazolamide and topiramate, all via oral gavage. Cerebrospinal fluid (CSF) secretion assays, and RT-qPCR and western blots on in vitro and in vivo CP, were used to investigate drug actions.
KEY RESULTS
We demonstrate that acetazolamide and topiramate achieved maximal ICP reduction within 120 min of administration, and in combination doubled the ICP reduction over a 24-h period. Chronic administration of acetazolamide or topiramate lowered ICP by 25%. Topiramate decreased CSF secretion by 40%. Chronic topiramate increased the gene expression of Slc12a2 and Slc4a10 and protein expression of the sodium-dependent chloride/bicarbonate exchanger (NCBE), whereas chronic acetazolamide did not affect the expression of assessed genes.
CONCLUSIONS AND IMPLICATIONS
Acetazolamide and topiramate are effective at lowering ICP at therapeutic levels. We provide the first evidence that topiramate lowers CSF secretion and that acetazolamide and topiramate may lower ICP via distinct molecular mechanisms. Thus, the combination of acetazolamide and topiramate may have utility for treating raised ICP.
Topics: Female; Rats; Animals; Acetazolamide; Intracranial Pressure; Topiramate
PubMed: 37553842
DOI: 10.1111/bph.16213 -
Archives of Oral Biology Nov 2020To investigate whether combination of acetazolamide and cisplatin can enhance the chemosensitivity of human head and neck squamous cell carcinoma (HNSCC) cell line TU868.
AIMS
To investigate whether combination of acetazolamide and cisplatin can enhance the chemosensitivity of human head and neck squamous cell carcinoma (HNSCC) cell line TU868.
METHODS
MTT assay was performed to determine the effect of acetazolamide, cisplatin and their combination on the proliferation of TU868 cells. Then the effect of these 2 drugs on the expression of proliferation-related and apoptosis-related proteins was detected by Western blot. Moreover, the effect of acetazolamide and cisplatin on the expression of aquaporin-1 was detected by RT-qPCR. Loss-of-function assays was performed to assess whether the effect of acetazolamide and cisplatin on TU868 cells was mediated by aquaporin-1. The effect of acetazolamide and cisplatin on tumor cell growth was confirmed in mice by testing the tumor growth size.
RESULTS
Acetazolamide and cisplatin treatment displayed synergistic effects on the inhibition of TU868 cell growth compared with the drugs used alone. Moreover, the acetazolamide/cisplatin combination could decrease the level of PCNA but increase the level of p53; decrease the ratio of Bcl-2/Bax and increase the expression of caspase-3 compared with the single drug treated group. Moreover, we found that the combination also significantly inhibits aquaporin-1 expression. Loss-of-function assays suggested that the anti-tumor effect of these 2 drugs was achieved via affecting aquaporin-1. Consistent with the in vitro assays, combined treatment with acetazolamide and cisplatin significantly inhibits the tumor growth in mice compared with the single drug treated group.
CONCLUSION
These results demonstrated that combined treatment with acetazolamide and cisplatin could synergistically inhibit the malignant development of HNSCC cells.
Topics: Acetazolamide; Animals; Antineoplastic Agents; Apoptosis; Aquaporin 1; Cell Line, Tumor; Cisplatin; Drug Therapy, Combination; Head and Neck Neoplasms; Humans; Mice; Squamous Cell Carcinoma of Head and Neck; Xenograft Model Antitumor Assays
PubMed: 32947166
DOI: 10.1016/j.archoralbio.2020.104905 -
Osteoporosis International : a Journal... Jan 2022Tumoral calcinosis (TC) is a rare disease characterized by periarticular soft tissue calcification. Some cases were reported in Africa and the Middle East. We report an...
Tumoral calcinosis (TC) is a rare disease characterized by periarticular soft tissue calcification. Some cases were reported in Africa and the Middle East. We report an 11-year-old Chinese girl presenting with recurrent multiple subcutaneous masses around the right elbow and hip regions. Although we found abnormalities in FGF23, a protein associated with phosphate metabolism, no positive results were observed in gene sequencing and analysis. The imaging features, laboratory examination, and pathology results confirmed our diagnosis. By using oral phosphorus-lowering drugs (acetazolamide) combined with complete surgical excision, good results were achieved, and no recurrence was reported during the follow-up of 18 months. We report a case of primary hyperphosphatemic TC. The combined use of oral phosphorus-lowering drugs (acetazolamide) and complete surgical excision produced good results, and no recurrence was reported during the follow-up of 18 months.
Topics: Calcinosis; Child; Female; Fibroblast Growth Factors; Humans; Hyperostosis, Cortical, Congenital; Hyperphosphatemia
PubMed: 34245344
DOI: 10.1007/s00198-021-06056-5 -
The Annals of Pharmacotherapy Nov 2023Acetazolamide has been used for diuretic-induced metabolic alkalosis, but the preferred dose, route, and frequency of administration remain unknown.
BACKGROUND
Acetazolamide has been used for diuretic-induced metabolic alkalosis, but the preferred dose, route, and frequency of administration remain unknown.
OBJECTIVE
The purpose of this study was to characterize dosing strategies and determine the effectiveness of intravenous (IV) and oral (PO) acetazolamide for patients with heart failure (HF) with diuretic-induced metabolic alkalosis.
METHODS
This was a multicenter, retrospective cohort study comparing the use of IV versus PO acetazolamide in patients with HF receiving at least 120 mg of furosemide for the treatment of metabolic alkalosis (serum bicarbonate CO ≥32). The primary outcome was the change in CO on the first basic metabolic panel (BMP) within 24 hours of the first dose of acetazolamide. Secondary outcomes included laboratory outcomes, such as change in bicarbonate, chloride, and incidence of hyponatremia and hypokalemia. This study was approved by the local institutional review board.
RESULTS
IV acetazolamide was given in 35 patients and PO acetazolamide was given in 35 patients. Patients in both groups were given a median of 500 mg of acetazolamide in the first 24 hours. For the primary outcome, there was a significant decrease in CO on the first BMP within 24 hours after patients received the IV acetazolamide (-2 [interquartile range, IQR: -2, 0] vs 0 [IQR: -3, 1], = 0.047). There were no differences in secondary outcomes.
CONCLUSION AND RELEVANCE
IV acetazolamide resulted in significantly decreased bicarbonate within 24 hours of administration. IV acetazolamide may be preferred to treat diuretic-induced metabolic alkalosis in patients with HF.
Topics: Humans; Acetazolamide; Diuretics; Carbonic Anhydrase Inhibitors; Bicarbonates; Retrospective Studies; Carbon Dioxide; Alkalosis; Heart Failure
PubMed: 36803069
DOI: 10.1177/10600280231154603 -
The New England Journal of Medicine Dec 2022
Topics: Humans; Acetazolamide; Heart Failure; Acid-Base Imbalance; Water-Electrolyte Imbalance; Urologic Diseases
PubMed: 36577116
DOI: 10.1056/NEJMc2214165 -
European Journal of Medicinal Chemistry Jan 2021Carbonic anhydrase (CA, EC 4.2.1.1) is an enzyme and a very omnipresent zinc metalloenzyme which catalyzed the reversible hydration and dehydration of carbon dioxide and... (Review)
Review
Carbonic anhydrase (CA, EC 4.2.1.1) is an enzyme and a very omnipresent zinc metalloenzyme which catalyzed the reversible hydration and dehydration of carbon dioxide and bicarbonate; a reaction which plays a crucial role in many physiological and pathological processes. Carbonic anhydrase is present in human (h) with sixteen different isoforms ranging from hCA I-hCA XV. All these isoforms are widely distributed in different tissues/organs and are associated with a range of pivotal physiological activities. Due to their involvement in various physiological roles, inhibitors of different human isoforms of carbonic anhydrase have found clinical applications for the treatment of various diseases including glaucoma, retinopathy, hemolytic anemia, epilepsy, obesity, and cancer. However, clinically used inhibitors of CA (acetazolamide, brinzolamide, dorzolamide, etc.) are not selective causing the undesirable side effects. One of the major hurdles in the design and development of carbonic anhydrase inhibitors is the lack of balanced isoform selectivity which thrived to new chemotypes. In this review, we have compiled the recent strategies of various researchers related to the development of carbonic anhydrase inhibitors belonging to different structural classes like pyrimidine, pyrazoline, selenourea, isatin, indole, etc. This review also summarizes the structure-activity relationships, analysis of isoform selectivity including mechanistic and in silico studies to afford ideas and to provide focused direction for the design and development of novel isoform-selective carbonic anhydrase inhibitors with therapeutic implications.
Topics: Acetazolamide; Animals; Antineoplastic Agents; Antioxidants; Carbonic Anhydrase Inhibitors; Carbonic Anhydrases; Humans; Indoles; Isatin; Molecular Docking Simulation; Organoselenium Compounds; Oxadiazoles; Protein Binding; Protein Isoforms; Pyrimidines; Structure-Activity Relationship; Sulfonamides; Thiazines; Thiophenes; Urea; Benzenesulfonamides
PubMed: 33121862
DOI: 10.1016/j.ejmech.2020.112923 -
Chest Feb 2020Sleep-disordered breathing (SDB), including OSA and central sleep apnea, is highly prevalent in patients with heart failure (HF). Multiple studies have reported this... (Review)
Review
Sleep-disordered breathing (SDB), including OSA and central sleep apnea, is highly prevalent in patients with heart failure (HF). Multiple studies have reported this high prevalence in asymptomatic as well as symptomatic patients with reduced left ventricular ejection fraction (HFrEF), as well as in those with HF with preserved ejection fraction. The acute pathobiologic consequences of OSA, including exaggerated sympathetic activity, oxidative stress, and inflammation, eventually could lead to progressive left ventricular dysfunction, repeated hospitalization, and excessive mortality. Large numbers of observational studies and a few small randomized controlled trials have shown improvement in various cardiovascular consequences of SDB with treatment. There are no long-term randomized controlled trials to show improved survival of patients with HF and treatment of OSA. One trial of positive airway pressure treatment of OSA included patients with HF and showed no improvement in clinical outcomes. However, any conclusions derived from this trial must take into account several important pitfalls that have been extensively discussed in the literature. With the role of positive airway pressure as the sole therapy for SDB in HF increasingly questioned, a critical examination of long-accepted concepts in this field is needed. The objective of this review was to incorporate recent advances in the field into a phenotype-based approach to the management of OSA in HF.
Topics: Acetazolamide; Carbon Dioxide; Carbonic Anhydrase Inhibitors; Continuous Positive Airway Pressure; Electric Stimulation Therapy; Exercise; Heart Failure; Humans; Hypoglossal Nerve; Muscle Hypotonia; Oxygen Inhalation Therapy; Pharyngeal Muscles; Phenotype; Sleep Apnea, Obstructive
PubMed: 31047953
DOI: 10.1016/j.chest.2019.02.407