Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 6.059
Filter
2.
BMJ Case Rep ; 17(8)2024 Aug 30.
Article in English | MEDLINE | ID: mdl-39214584

ABSTRACT

A woman in her mid-60s who is a high hypermetrope presented with bilateral eye pain and headache approximately 1 hour after taking a single dose of a widely available decongestant containing paracetamol, guaifenesin and phenylephrine hydrochloride for coryzal symptoms. She had previous successful bilateral peripheral iridotomies performed for narrow angles. At presentation, her intraocular pressures (IOPs) were significantly raised at 72 mm Hg and 66 mm Hg in the right and left eye, respectively, with bilateral corneal oedema. Her IOP was normalised with urgent treatment using 500 mg intravenous acetazolamide, pilocarpine 2%, dexamethasone 0.1% and IOP-lowering drops. She was listed for cataract surgery and was advised to avoid the precipitating agent and other over-the-counter decongestants. This is the first reported case of bilateral angle closure triggered by a decongestant with such a combination of ingredients. Clinicians should be aware of this rare side effect for prompt diagnosis and management.


Subject(s)
Acetaminophen , Acetazolamide , Glaucoma, Angle-Closure , Humans , Glaucoma, Angle-Closure/chemically induced , Glaucoma, Angle-Closure/drug therapy , Female , Middle Aged , Acetazolamide/therapeutic use , Acetazolamide/administration & dosage , Acetaminophen/adverse effects , Acetaminophen/administration & dosage , Acetaminophen/therapeutic use , Phenylephrine/adverse effects , Phenylephrine/administration & dosage , Phenylephrine/therapeutic use , Nonprescription Drugs/adverse effects , Nonprescription Drugs/administration & dosage , Guaifenesin/adverse effects , Guaifenesin/administration & dosage , Guaifenesin/therapeutic use , Nasal Decongestants/adverse effects , Nasal Decongestants/administration & dosage , Intraocular Pressure/drug effects , Multi-Ingredient Cold, Flu, and Allergy Medications/adverse effects , Pilocarpine/therapeutic use , Pilocarpine/administration & dosage , Pilocarpine/adverse effects , Dexamethasone/administration & dosage , Dexamethasone/therapeutic use , Dexamethasone/adverse effects , Eye Pain/chemically induced , Eye Pain/etiology , Acute Disease
3.
Pediatr Neurol ; 160: 32-37, 2024 Nov.
Article in English | MEDLINE | ID: mdl-39178652

ABSTRACT

BACKGROUND: Topiramate is often considered as a second-line medication for the treatment of pseudotumor cerebri syndrome (PTCS), but limited studies exist that evaluate its efficacy in children. METHODS: Retrospective study of patients aged <21 years with PTCS who were treated with topiramate alone or in combination with acetazolamide was performed. Data regarding clinical courses and visual outcomes were recorded. RESULTS: A total of 46 patients were identified. Three (6.5%) patients were treated with topiramate alone, 31 (67.4%) transitioned to topiramate from acetazolamide, and 12 (26.1%) took both topiramate and acetazolamide concurrently. The median time to resolution of papilledema on topiramate was 0.57 years (interquartile range 0.32 to 0.84). Among eyes with papilledema graded on the Frisen scale at topiramate initiation, 40 of 57 (70.2%) were grade 1, nine of 57 (15.8%) were grade 2, and eight of 57 (14.0%) were grade 3. Twenty-seven of 46 (58.7%) reported headache improvement after starting topiramate. The mean dose of topiramate was 1.3 ± 0.8 mg/kg/day. The most common side effect was patient report of cognitive slowing (10 of 46 [21.7%]). All patients on topiramate monotherapy who were compliant with treatment and follow-up had resolution of papilledema with no evidence of visual function loss. CONCLUSIONS: Topiramate can effectively treat PTCS in children with mild to moderate papilledema or in those unable to tolerate acetazolamide. More research is needed to assess the efficacy of topiramate for higher grade papilledema.


Subject(s)
Acetazolamide , Pseudotumor Cerebri , Topiramate , Humans , Topiramate/administration & dosage , Topiramate/adverse effects , Topiramate/pharmacology , Pseudotumor Cerebri/drug therapy , Pseudotumor Cerebri/chemically induced , Child , Female , Male , Retrospective Studies , Acetazolamide/adverse effects , Acetazolamide/therapeutic use , Acetazolamide/administration & dosage , Adolescent , Papilledema/drug therapy , Papilledema/chemically induced , Anticonvulsants/adverse effects , Anticonvulsants/administration & dosage , Child, Preschool , Treatment Outcome , Drug Therapy, Combination , Carbonic Anhydrase Inhibitors/adverse effects , Carbonic Anhydrase Inhibitors/administration & dosage , Fructose/analogs & derivatives , Fructose/adverse effects , Fructose/therapeutic use , Fructose/administration & dosage
4.
Heart Fail Rev ; 29(5): 1039-1047, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38985385

ABSTRACT

Acute heart failure (AHF) often leads to unfavorable outcomes due to fluid overload. While diuretics are the cornerstone treatment, acetazolamide may enhance diuretic efficiency by reducing sodium reabsorption. We performed a systematic review and meta-analysis on the effects of acetazolamide as an add-on therapy in patients with AHF compared to diuretic therapy. PubMed, Embase, and Cochrane databases were searched for randomized controlled trials (RCT). A random-effects model was employed to compute mean differences and risk ratios. Statistical analysis was performed using R software. The GRADE approach was used to rate the certainty of the evidence. We included 4 RCTs with 634 patients aged 68 to 81 years. Over a mean follow-up of 3 days to 34 months, acetazolamide significantly increased diuresis (MD 899.2 mL; 95% CI 249.5 to 1549; p < 0.01) and natriuresis (MD 72.44 mmol/L; 95% CI 39.4 to 105.4; p < 0.01) after 48 h of its administration. No association was found between acetazolamide use and WRF (RR 2.4; 95% CI 0.4 to 14.2; p = 0.3) or all-cause mortality (RR 1.2; 95% CI 0.8 to 1.9; p = 0.3). Clinical decongestion was significantly higher in the intervention group (RR 1.35; 95% CI 1.09 to 1.68; p = 0.01). Acetazolamide is an effective add-on therapy in patients with AHF, increasing diuresis, natriuresis, and clinical decongestion, but it was not associated with differences in mortality.


Subject(s)
Acetazolamide , Diuretics , Heart Failure , Randomized Controlled Trials as Topic , Acetazolamide/therapeutic use , Humans , Heart Failure/drug therapy , Heart Failure/physiopathology , Heart Failure/mortality , Acute Disease , Diuretics/therapeutic use , Carbonic Anhydrase Inhibitors/therapeutic use , Treatment Outcome , Aged
5.
Rev Neurol ; 79(3): 89-93, 2024 Aug 01.
Article in Spanish | MEDLINE | ID: mdl-39007860

ABSTRACT

INTRODUCTION: Idiopathic intracranial hypertension (IIH) or benign intracranial hypertension is a rare disease in childhood. The clinical presentation in pediatric patients can be very variable, being more unespecific in younger patients. PATIENTS AND METHODS: A retrospective descriptive study was carried out on patients diagnosed of IIH in the last eight years (2016-2023) in the neuropediatrics unit of a tertiary hospital. In the present study, the clinical-epidemiological characteristics and the diagnostic-therapeutic procedure carried out in each case were analyzed. RESULTS: We studied 14 patients, 57% were women. The average age at diagnosis was 9 years, headache was the most common reason for consultation. In all patients, papilledema was found in the fundus and neuroimaging didn´t find alterations. Optical coherence tomography has been carried out in 78.5% of the sample, > 80% of patients showed thickening of the retinal nerve fiber layer. All patients had a high cerebrospinal fluid opening pressure (>25 cmH2O). 57% of patients required treatment with acetazolamide, a carbonic anhydrase inhibito. In all patients the resolution was complete, however almost 30% of them have presented recurrences during follow-up. CONCLUSIONS: In recent years there has been an increase in the incidence of this entity, making early diagnosis and treatment essential to avoid possible irreversible damage.


TITLE: Hipertensión intracraneal idiopática. Revisión de nuestra experiencia en los últimos ocho años (2016-2023).Introducción. La hipertensión intracraneal idiopática (HII), o hipertensión intracraneal benigna, es una enfermedad poco frecuente en la infancia. La presentación clínica en pacientes pediátricos puede ser muy variable, y es más inespecífica a menor edad. Pacientes y métodos. Se ha realizado un estudio descriptivo retrospectivo de los pacientes diagnosticados de HII en los últimos ocho años (2016-2023) en la consulta de neuropediatría de un hospital de tercer nivel. En el presente estudio se analizaron las características clinicoepidemiológicas y el procedimiento diagnosticoterapéutico llevado a cabo en cada caso. Resultados. Se estudió a 14 pacientes, de los cuales el 57% eran mujeres. La edad media en el momento del diagnóstico fue de 9 años, y la cefalea fue el motivo de consulta más habitual. En todos los pacientes se constató papiledema en el fondo de ojo y una prueba de neuroimagen sin alteraciones. Se llevó a cabo una tomografía de coherencia óptica en el 78,5% de la muestra, y >80% de los pacientes presentaba engrosamiento de la capa de fibras nerviosas retiniana. La totalidad de los pacientes presentaba una presión de apertura de líquido cefalorraquídeo elevada (> 25 cmH2O). El 57% de los pacientes precisó como tratamiento acetazolamida, un inhibidor de la anhidrasa carbónica. En todos los pacientes la resolución fue completa; sin embargo, casi el 30% de ellos presentó recurrencias durante el seguimiento. Conclusiones. En los últimos años se ha mostrado un aumento en la incidencia de esta entidad, y es fundamental un diagnóstico y un tratamiento precoces para evitar posibles secuelas irreversibles.


Subject(s)
Pseudotumor Cerebri , Humans , Female , Retrospective Studies , Male , Pseudotumor Cerebri/diagnosis , Pseudotumor Cerebri/complications , Child , Adolescent , Child, Preschool , Acetazolamide/therapeutic use , Time Factors , Tomography, Optical Coherence , Papilledema/etiology , Papilledema/diagnosis
6.
Int J Pharm ; 661: 124391, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38936444

ABSTRACT

The complex structure of the eye poses challenges in delivering drugs effectively, which can be circumvented by employing nanotechnologies. The present study aimed to prepareacetazolamide-loadedleciplex (ACZ - LP) using a simple one-step fabrication approach followed byoptimization employing a 32 Full Factorial Design. The ACZ - LP demonstrated high entrapment efficiency (93.25 ± 2.32 %), average diameter was recorded around 171.03 ± 3.32 with monodisperse size distribution and zeta potential of 41.33 ± 2.10 mV. Invitro release and ex vivo permeation studies of prepared formulation demonstrated an initial burst release in 1 h followed by sustained release pattern as compared to plain acetazolamide solution. Moreover, an ex vivo corneal drug retention (27.05 ± 1.20 %) and in vitro mucoadhesive studies with different concentration of mucin indicated strong electrostatic bonding confirming the mucoadhesive characteristics of the formulation. Additionally, the histopathological studies ensured that the formulation was non-irritant and nontoxic while and HET-CAM ensured substantial tolerability of the formulation. The in vivo pharmacodynamic investigation carried out on a rabbit model demonstrated that treatment with ACZ - LP resulted in a significant and prolonged reduction in intraocular pressure as compared to plain acetazolamide solution, acetazolamide oral tablet, and Brinzox®. In summary, the ACZ - LP is anefficient and versatile drug delivery approach which demonstrates significant potential in controlling glaucoma.


Subject(s)
Acetazolamide , Carbonic Anhydrase Inhibitors , Drug Delivery Systems , Drug Liberation , Intraocular Pressure , Acetazolamide/administration & dosage , Acetazolamide/pharmacokinetics , Acetazolamide/chemistry , Acetazolamide/pharmacology , Animals , Rabbits , Carbonic Anhydrase Inhibitors/administration & dosage , Carbonic Anhydrase Inhibitors/pharmacokinetics , Carbonic Anhydrase Inhibitors/chemistry , Carbonic Anhydrase Inhibitors/pharmacology , Intraocular Pressure/drug effects , Cornea/metabolism , Cornea/drug effects , Male , Administration, Ophthalmic , Particle Size , Drug Carriers/chemistry
7.
Mol Pharm ; 21(7): 3383-3394, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38831541

ABSTRACT

Carbonic anhydrase IX (CAIX), a zinc metal transmembrane protein, is highly expressed in 95% of clear cell renal cell carcinomas (ccRCCs). A positron emission tomography (PET) probe designed to target CAIX in nuclear medicine imaging technology can achieve precise positioning, is noninvasive, and can be used to monitor CAIX expression in lesions in real time. In this study, we constructed a novel acetazolamide dual-targeted small-molecule probe [68Ga]Ga-LF-4, which targets CAIX by binding to a specific amino acid sequence. After attenuation correction, the radiolabeling yield reached 66.95 ± 0.57% (n = 5) after 15 min of reaction and the radiochemical purity reached 99% (n = 5). [68Ga]Ga-LF-4 has good in vitro and in vivo stability, and in vivo safety and high affinity for CAIX, with a Kd value of 6.62 nM. Moreover, [68Ga]Ga-LF-4 could be quickly cleared from the blood in vivo. The biodistribution study revealed that the [68Ga]Ga-LF-4 signal was concentrated in the heart, lung, and kidney after administration, which was the same as that observed in the micro-PET/CT study. In a ccRCC patient-derived xenograft (PDX) model, the signal significantly accumulated in the tumor after administration, where it was retained for up to 4 h. After competitive blockade with LF-4, uptake at the tumor site was significantly reduced. The SUVmax of the probe [68Ga]Ga-LF-4 at the ccRCC tumor site was three times greater than that in the PC3 group with low CAIX expression at 30 min (ccRCC vs PC3:1.86 ± 0.03 vs 0.62 ± 0.01, t = 48.2, P < 0.0001). These results indicate that [68Ga]Ga-LF-4 is a novel small-molecule probe that targets CAIX and can be used to image localized and metastatic ccRCC lesions.


Subject(s)
Carbonic Anhydrase IX , Carcinoma, Renal Cell , Gallium Radioisotopes , Kidney Neoplasms , Animals , Carbonic Anhydrase IX/metabolism , Carbonic Anhydrase IX/antagonists & inhibitors , Humans , Mice , Carcinoma, Renal Cell/diagnostic imaging , Carcinoma, Renal Cell/metabolism , Kidney Neoplasms/diagnostic imaging , Kidney Neoplasms/metabolism , Tissue Distribution , Cell Line, Tumor , Radiopharmaceuticals/pharmacokinetics , Radiopharmaceuticals/chemistry , Mice, Nude , Antigens, Neoplasm/metabolism , Molecular Probes/pharmacokinetics , Molecular Probes/chemistry , Positron Emission Tomography Computed Tomography/methods , Acetazolamide/pharmacokinetics , Female , Mice, Inbred BALB C , Positron-Emission Tomography/methods , Male , Xenograft Model Antitumor Assays
8.
Ophthalmic Surg Lasers Imaging Retina ; 55(7): 415-417, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38917399

ABSTRACT

Morning glory disc anomaly is a rare congenital anomaly affecting the optic disc and is frequently associated with retinal detachment. This report presents a unique case of a 10-year-old boy with morning glory disc anomaly and serous retinal detachment, treated with oral acetazolamide. Remarkably, half of the retina exhibiting bullous detachment was reattached leading to full recovery of vision within a few days after starting acetazol-amide treatment. There was no recurrence after discontinuation of medication. Oral acetazolamide can be considered an alternative treatment option for retinal detachment associated with morning glory disc anomaly of non-rhegmatogenous origin. [Ophthalmic Surg Lasers Imaging Retina 2024;55:415-417.].


Subject(s)
Acetazolamide , Carbonic Anhydrase Inhibitors , Optic Disk , Retinal Detachment , Tomography, Optical Coherence , Humans , Acetazolamide/therapeutic use , Acetazolamide/administration & dosage , Male , Child , Retinal Detachment/diagnosis , Retinal Detachment/drug therapy , Retinal Detachment/etiology , Administration, Oral , Optic Disk/abnormalities , Carbonic Anhydrase Inhibitors/therapeutic use , Carbonic Anhydrase Inhibitors/administration & dosage , Tomography, Optical Coherence/methods , Visual Acuity , Fluorescein Angiography/methods
9.
Int J Mol Sci ; 25(9)2024 Apr 27.
Article in English | MEDLINE | ID: mdl-38732005

ABSTRACT

In calcium nephrolithiasis (CaNL), most calcium kidney stones are identified as calcium oxalate (CaOx) with variable amounts of calcium phosphate (CaP), where CaP is found as the core component. The nucleation of CaP could be the first step of CaP+CaOx (mixed) stone formation. High urinary supersaturation of CaP due to hypercalciuria and an elevated urine pH have been described as the two main factors in the nucleation of CaP crystals. Our previous in vivo findings (in mice) show that transient receptor potential canonical type 3 (TRPC3)-mediated Ca2+ entry triggers a transepithelial Ca2+ flux to regulate proximal tubular (PT) luminal [Ca2+], and TRPC3-knockout (KO; -/-) mice exhibited moderate hypercalciuria and microcrystal formation at the loop of Henle (LOH). Therefore, we utilized TRPC3 KO mice and exposed them to both hypercalciuric [2% calcium gluconate (CaG) treatment] and alkalineuric conditions [0.08% acetazolamide (ACZ) treatment] to generate a CaNL phenotype. Our results revealed a significant CaP and mixed crystal formation in those treated KO mice (KOT) compared to their WT counterparts (WTT). Importantly, prolonged exposure to CaG and ACZ resulted in a further increase in crystal size for both treated groups (WTT and KOT), but the KOT mice crystal sizes were markedly larger. Moreover, kidney tissue sections of the KOT mice displayed a greater CaP and mixed microcrystal formation than the kidney sections of the WTT group, specifically in the outer and inner medullary and calyceal region; thus, a higher degree of calcifications and mixed calcium lithiasis in the kidneys of the KOT group was displayed. In our effort to find the Ca2+ signaling pathophysiology of PT cells, we found that PT cells from both treated groups (WTT and KOT) elicited a larger Ca2+ entry compared to the WT counterparts because of significant inhibition by the store-operated Ca2+ entry (SOCE) inhibitor, Pyr6. In the presence of both SOCE (Pyr6) and ROCE (receptor-operated Ca2+ entry) inhibitors (Pyr10), Ca2+ entry by WTT cells was moderately inhibited, suggesting that the Ca2+ and pH levels exerted sensitivity changes in response to ROCE and SOCE. An assessment of the gene expression profiles in the PT cells of WTT and KOT mice revealed a safeguarding effect of TRPC3 against detrimental processes (calcification, fibrosis, inflammation, and apoptosis) in the presence of higher pH and hypercalciuric conditions in mice. Together, these findings show that compromise in both the ROCE and SOCE mechanisms in the absence of TRPC3 under hypercalciuric plus higher tubular pH conditions results in higher CaP and mixed crystal formation and that TRPC3 is protective against those adverse effects.


Subject(s)
Calcium Oxalate , Hypercalciuria , Kidney Calculi , Mice, Knockout , Animals , Hypercalciuria/metabolism , Hypercalciuria/genetics , Hydrogen-Ion Concentration , Mice , Calcium Oxalate/metabolism , Kidney Calculi/metabolism , Kidney Calculi/etiology , Kidney Calculi/pathology , Calcium Phosphates/metabolism , Nephrolithiasis/metabolism , Nephrolithiasis/genetics , Nephrolithiasis/pathology , Calcium/metabolism , TRPC Cation Channels/metabolism , TRPC Cation Channels/genetics , Kidney Tubules, Proximal/metabolism , Kidney Tubules, Proximal/pathology , Male , Disease Models, Animal , Mice, Inbred C57BL , Acetazolamide/pharmacology
11.
Br J Clin Pharmacol ; 90(7): 1751-1755, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38770584

ABSTRACT

To our knowledge, no prior study has analysed a possible association between acetazolamide and pulmonary oedema. The aim of this study was to use data from the EudraVigilance to detect a safety signal for acetazolamide-induced pulmonary oedema. We performed a disproportionality analysis (case-noncase method), calculating reporting odds ratios (RORs) up to 22 February 2024. Among 11 684 208 spontaneous cases of adverse reactions registered in EudraVigilance, 38 275 were pulmonary oedemas. Acetazolamide was involved in 31 cases. In more than half of those cases, the patients received a single dose of acetazolamide after undergoing cataract surgery: latency was 10-90 min. Remarkably, there were five cases of positive rechallenge and six cases resulted in death. The ROR for acetazolamide was 3.63 (95% CI 2.55-5.17). Disproportionality was also observed in VigiBase®: ROR 4.44 (95% CI 3.34-5.90). Our study confirms a signal that suggests a risk of serious pulmonary oedema associated with acetazolamide.


Subject(s)
Acetazolamide , Databases, Factual , Pulmonary Edema , Humans , Acetazolamide/adverse effects , Pulmonary Edema/chemically induced , Pulmonary Edema/epidemiology , Male , Female , Middle Aged , Aged , Databases, Factual/statistics & numerical data , Adverse Drug Reaction Reporting Systems/statistics & numerical data , Adult , Carbonic Anhydrase Inhibitors/adverse effects , Carbonic Anhydrase Inhibitors/administration & dosage , Pharmacovigilance , Aged, 80 and over
12.
Neurosurg Clin N Am ; 35(3): 287-291, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38782521

ABSTRACT

Idiopathic intracranial hypertension is defined by headaches and a decline in visual acuity due to increased intracranial pressure. Treatment options historically included weight loss, acetazolamide, and/or cerebrospinal fluid diversion surgery. Recent understanding of the contributions of dural venous sinus hypertension and stenosis has led to venous sinus stenting as a treatment option.


Subject(s)
Pseudotumor Cerebri , Humans , Acetazolamide/therapeutic use , Cranial Sinuses/surgery , Intracranial Hypertension/therapy , Pseudotumor Cerebri/surgery , Pseudotumor Cerebri/therapy , Stents
13.
Exp Physiol ; 109(7): 1080-1098, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38747161

ABSTRACT

High altitude (HA) ascent imposes systemic hypoxia and associated risk of acute mountain sickness. Acute hypoxia elicits a hypoxic ventilatory response (HVR), which is augmented with chronic HA exposure (i.e., ventilatory acclimatization; VA). However, laboratory-based HVR tests lack portability and feasibility in field studies. As an alternative, we aimed to characterize area under the curve (AUC) calculations on Fenn diagrams, modified by plotting portable measurements of end-tidal carbon dioxide ( P ETC O 2 ${P_{{\mathrm{ETC}}{{\mathrm{O}}_{\mathrm{2}}}}}$ ) against peripheral oxygen saturation ( S p O 2 ${S_{{\mathrm{p}}{{\mathrm{O}}_{\mathrm{2}}}}}$ ) to characterize and quantify VA during incremental ascent to HA (n = 46). Secondarily, these participants were compared with a separate group following the identical ascent profile whilst self-administering a prophylactic oral dose of acetazolamide (Az; 125 mg BID; n = 20) during ascent. First, morning P ETC O 2 ${P_{{\mathrm{ETC}}{{\mathrm{O}}_{\mathrm{2}}}}}$ and S p O 2 ${S_{{\mathrm{p}}{{\mathrm{O}}_{\mathrm{2}}}}}$ measurements were collected on 46 acetazolamide-free (NAz) lowland participants during an incremental ascent over 10 days to 5160 m in the Nepal Himalaya. AUC was calculated from individually constructed Fenn diagrams, with a trichotomized split on ranked values characterizing the smallest, medium, and largest magnitudes of AUC, representing high (n = 15), moderate (n = 16), and low (n = 15) degrees of acclimatization. After characterizing the range of response magnitudes, we further demonstrated that AUC magnitudes were significantly smaller in the Az group compared to the NAz group (P = 0.0021), suggesting improved VA. These results suggest that calculating AUC on modified Fenn diagrams has utility in assessing VA in large groups of trekkers during incremental ascent to HA, due to the associated portability and congruency with known physiology, although this novel analytical method requires further validation in controlled experiments. HIGHLIGHTS: What is the central question of this study? What are the characteristics of a novel methodological approach to assess ventilatory acclimatization (VA) with incremental ascent to high altitude (HA)? What is the main finding and its importance? Area under the curve (AUC) magnitudes calculated from modified Fenn diagrams were significantly smaller in trekkers taking an oral prophylactic dose of acetazolamide compared to an acetazolamide-free group, suggesting improved VA. During incremental HA ascent, quantifying AUC using modified Fenn diagrams is feasible to assess VA in large groups of trekkers with ascent, although this novel analytical method requires further validation in controlled experiments.


Subject(s)
Acclimatization , Acetazolamide , Altitude Sickness , Altitude , Hypoxia , Acetazolamide/pharmacology , Humans , Acclimatization/physiology , Male , Adult , Altitude Sickness/physiopathology , Female , Hypoxia/physiopathology , Carbonic Anhydrase Inhibitors/pharmacology , Young Adult , Carbon Dioxide/metabolism , Oxygen Saturation/physiology , Oxygen Saturation/drug effects , Pulmonary Ventilation/drug effects , Pulmonary Ventilation/physiology
14.
Am J Otolaryngol ; 45(4): 104317, 2024.
Article in English | MEDLINE | ID: mdl-38729011

ABSTRACT

OBJECTIVES: Tegmen and superior semicircular canal defects have been well studied, yet the factors contributing to their onset and progression are widely debated. The clinical utility of intraoperative intracranial pressure measurements has yet to be tested. This report aims to use intraoperative opening pressure and concurrent superior semicircular canal dehiscence (SSCD) to analyze factors influencing disease course and clinical outcomes in patients with tegmen dehiscence. METHODS: A retrospective analysis of 61 patients who underwent tegmen defect repair was performed. Multiple variables of interest including body mass index (BMI), presence of SSCD, presence of dural venous sinus stenosis, opening pressure, and acetazolamide therapy use were recorded. The cohort was divided into those with or without concurrent SSCD and those presenting with or without cerebrospinal fluid (CSF) leak for analysis. RESULTS: A linear relationship between opening pressure and BMI (p = 0.009) was noted; however, intraoperative opening pressure was not associated with disease outcome. Concurrent SSCD was present in 25 % of patients, while 62 % presented with CSF leak. The concurrent SSCD group exhibited higher opening pressure, higher likelihood of having dural sinus stenosis, and higher likelihood of being discharged on acetazolamide. The CSF leak group had higher likelihood of obstructive sleep apnea and persistent symptoms. CONCLUSIONS: In patients undergoing tegmen defect repair, concurrent SSCD suggests increased disease severity. The presence of preoperative CSF leak predicts persistent symptoms following repair. BMI is linearly correlated with intracranial pressure in these patients.


Subject(s)
Cerebrospinal Fluid Leak , Semicircular Canal Dehiscence , Semicircular Canals , Humans , Male , Female , Retrospective Studies , Middle Aged , Cerebrospinal Fluid Leak/etiology , Cerebrospinal Fluid Leak/surgery , Semicircular Canals/surgery , Semicircular Canal Dehiscence/surgery , Semicircular Canal Dehiscence/complications , Treatment Outcome , Adult , Body Mass Index , Aged , Intracranial Pressure , Postoperative Complications/etiology , Acetazolamide
15.
Wilderness Environ Med ; 35(3): 328-331, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38725416

ABSTRACT

Prophylactic use of acetazolamide (ACZ) to prevent acute mountain sickness (AMS) is a common practice among high altitude travelers and mountaineers. With its use comes a possible risk of acute kidney injury (AKI). We present a case in which a 56-year-old male hiker in Grand Canyon National Park developed acute exertional rhabdomyolysis and subsequent AKI while taking prophylactic ACZ to prevent AMS. This medication was prescribed despite the hiker encountering only moderate altitude at Grand Canyon with a planned descent within <24 h. The resulting AKI was determined to be the combined result of acute exertional rhabdomyolysis and dehydration/hypovolemia, with the ACZ, a diuretic, as a contributing factor. Medical providers need to recognize the risks/benefits with ACZ use for AMS prophylaxis and avoid prescribing it to individuals whose altitude exposure and activity fall outside the clinical practice guidelines recommended for use.


Subject(s)
Acetazolamide , Acute Kidney Injury , Altitude Sickness , Mountaineering , Humans , Acetazolamide/adverse effects , Acetazolamide/therapeutic use , Male , Acute Kidney Injury/chemically induced , Acute Kidney Injury/prevention & control , Middle Aged , Altitude Sickness/drug therapy , Altitude Sickness/prevention & control , Mountaineering/injuries , Rhabdomyolysis/chemically induced , Carbonic Anhydrase Inhibitors/adverse effects , Carbonic Anhydrase Inhibitors/therapeutic use
16.
JACC Heart Fail ; 12(8): 1396-1405, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38739124

ABSTRACT

BACKGROUND: Limited evidence exists regarding efficacy and safety of diuretic regimens in ambulatory, congestion-refractory, chronic heart failure (CHF) patients. OBJECTIVES: The authors sought to compare the potency and safety of commonly used diuretic regimens in CHF patients. METHODS: A prospective, randomized, open-label, crossover study conducted in NYHA functional class II to IV CHF patients, treated in an ambulatory day-care unit. Each patient received 3 different diuretic regimens: intravenous (IV) furosemide 250 mg; IV furosemide 250 mg plus oral metolazone 5 mg; and IV furosemide 250 mg plus IV acetazolamide 500 mg. Treatments were administered once a week, in 1 of 6 randomized sequences. The primary endpoint was total sodium excretion, and the secondary was total urinary volume excreted, both measured for 6 hours post-treatment initiation. RESULTS: A total of 42 patients were recruited. Administration of furosemide plus metolazone resulted in the highest weight of sodium excreted, 4,691 mg (95% CI: 4,153-5,229 mg) compared with furosemide alone, 3,835 mg (95% CI: 3,279-4,392 mg; P = 0.015) and to furosemide plus acetazolamide 3,584 mg (95% CI: 3,020-4,148 mg; P = 0.001). Furosemide plus metolazone resulted in 1.84 L of urine (95% CI: 1.63-2.05 L), compared with 1.58 L (95% CI: 1.37-1.8); P = 0.039 collected following administration of furosemide plus acetazolamide and 1.71 L (95% CI: 1.49-1.93 L) following furosemide alone. The incidence of worsening renal function was significantly higher when adding metolazone (39%) to furosemide compared with furosemide alone (16%) and to furosemide plus acetazolamide (2.6%) (P < 0.001). CONCLUSIONS: In ambulatory CHF patients, furosemide plus metolazone resulted in a significantly higher natriuresis compared with IV furosemide alone or furosemide plus acetazolamide.


Subject(s)
Acetazolamide , Cross-Over Studies , Diuretics , Furosemide , Heart Failure , Metolazone , Humans , Heart Failure/drug therapy , Heart Failure/physiopathology , Furosemide/administration & dosage , Furosemide/therapeutic use , Male , Female , Diuretics/administration & dosage , Diuretics/therapeutic use , Acetazolamide/administration & dosage , Acetazolamide/therapeutic use , Metolazone/administration & dosage , Aged , Prospective Studies , Middle Aged , Drug Therapy, Combination , Diuresis/drug effects , Treatment Outcome
17.
Eye (Lond) ; 38(12): 2472-2481, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38789788

ABSTRACT

Idiopathic intracranial hypertension (IIH) is a neuro-ophthalmological condition characterised by a raised intracranial pressure and papilloedema that causes disabling headaches. The main risk factors of female sex and living with obesity have been known for some time, however the knowledge of the underlying pathophysiology is evolving. Papilloedema can impact the visual function, and the majority of people are offered acetazolamide. Those with sight threatening disease need urgent management, though there is little high quality evidence to recommend any particular surgical intervention. Headache treatment is an unmet clinical need and simple medication overuse advice has the potential to reduce the chronification of migraine-like headaches. IIH is emerging as a systemic metabolic disease distinct from people living with obesity alone. While weight loss is the main stay of disease modifying therapy this is challenging to access and many healthcare professionals that manage the condition have no formal training or accessible pathways for weight management. The aim of this "how to do it" article is to present the latest advances in knowledge of IIH that we pragmatically included in routine clinical care for people living with the condition.


Subject(s)
Papilledema , Pseudotumor Cerebri , Humans , Pseudotumor Cerebri/physiopathology , Pseudotumor Cerebri/therapy , Pseudotumor Cerebri/diagnosis , Pseudotumor Cerebri/complications , Papilledema/diagnosis , Papilledema/physiopathology , Papilledema/therapy , Papilledema/etiology , Acetazolamide/therapeutic use , Risk Factors , Obesity/complications , Obesity/physiopathology , Carbonic Anhydrase Inhibitors/therapeutic use , Disease Management
18.
Magn Reson Imaging ; 110: 35-42, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38574981

ABSTRACT

BACKGROUND: Paired cerebral blood flow (CBF) measurement is usually acquired before and after vasoactive stimulus to estimate cerebrovascular reserve (CVR). However, CVR may be confounded because of variations in time-to-maximum CBF response (tmax) following acetazolamide injection. With a mathematical model, CVR can be calculated insensitive to variations in tmax, and a model offers the possibility to calculate additional model-derived parameters. A model that describes the temporal CBF response following a vasodilating acetazolamide injection is proposed and evaluated. METHODS: A bi-exponential model was adopted and fitted to four CBF measurements acquired using arterial spin labelling before and initialised at 5, 15 and 25 min after acetazolamide injection in a total of fifteen patients with Moyamoya disease. Curve fitting was performed using a non-linear least squares method with a priori constraints based on simulations. RESULTS: Goodness of fit (mean absolute error) varied between 0.30 and 0.62 ml·100 g-1·min-1. Model-derived CVR was significantly higher compared to static CVR measures. Maximum CBF increase occurred earlier in healthy- compared to diseased vascular regions. CONCLUSIONS: The proposed mathematical model offers the possibility to calculate CVR insensitive to variations in time to maximum CBF response which gives a more detailed characterisation of CVR compared to static CVR measures. Although the mathematical model adapts generally well to this dataset of patients with MMD it should be considered as experimental; hence, further studies in healthy populations and other patient cohorts are warranted.


Subject(s)
Acetazolamide , Cerebrovascular Circulation , Moyamoya Disease , Humans , Moyamoya Disease/diagnostic imaging , Moyamoya Disease/physiopathology , Moyamoya Disease/drug therapy , Acetazolamide/pharmacology , Cerebrovascular Circulation/drug effects , Female , Male , Adult , Middle Aged , Models, Theoretical , Young Adult , Vasodilator Agents/pharmacology , Magnetic Resonance Imaging , Brain/diagnostic imaging , Brain/blood supply
19.
Klin Monbl Augenheilkd ; 241(4): 554-558, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38653306

ABSTRACT

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.


Subject(s)
Acetazolamide , Myopia , Humans , Acetazolamide/therapeutic use , Acetazolamide/adverse effects , Acetazolamide/administration & dosage , Male , Adult , Myopia/chemically induced , Myopia/drug therapy , Carbonic Anhydrase Inhibitors/adverse effects , Carbonic Anhydrase Inhibitors/administration & dosage , Carbonic Anhydrase Inhibitors/therapeutic use , Acute Disease , Treatment Outcome
20.
Toxicol Appl Pharmacol ; 486: 116919, 2024 May.
Article in English | MEDLINE | ID: mdl-38580201

ABSTRACT

BACKGROUND: Idiopathic intracranial hypertension (IIH) is a disease characterized by elevated intracranial pressure (ICP) and is a disease of young females. The first line pharmacological treatments include acetazolamide and topiramate and given the nature of IIH patients and the dosing regimen of these drugs, their effect on the endocrine system is important to evaluate. We aimed to assess the effects of acetazolamide and topiramate on steroid profiles in relevant endocrine tissues. METHODS: Female Sprague Dawley rats received chronic clinically equivalent doses of acetazolamide or topiramate by oral gavage and were sacrificed in estrus. Tissue specific steroid profiles of lateral ventricle CP, 4th ventricle CP, CSF, serum, uterine horn and fundus, ovaries, adrenal glands and pituitary glands were assessed by quantitative targeted LC-MS/MS. We determined luteinizing hormone (LH) and follicle stimulating hormones (FSH) levels in paired serum by ELISA. RESULTS: Topiramate increased the concentration of estradiol and decreased the concentration of DHEA in lateral choroid plexus. Moreover, it decreased the concentration of androstenediol in the pituitary gland. Topiramate increased serum LH. Acetazolamide decreased progesterone levels in serum and uterine fundus and increased corticosteroid levels in the adrenal glands. CONCLUSION: These results demonstrate that both acetazolamide and topiramate have endocrine disrupting effects in rats. Topiramate primarily targeted the choroid plexus and the pituitary gland while acetazolamide had broader systemic effects. Furthermore, topiramate predominantly targeted sex hormones, whereas acetazolamide widely affected all classes of hormones. A similar effect in humans has not yet been documented but these concerning findings warrants further investigations.


Subject(s)
Acetazolamide , Endocrine Disruptors , Estrus , Rats, Sprague-Dawley , Topiramate , Animals , Female , Topiramate/pharmacology , Acetazolamide/pharmacology , Acetazolamide/toxicity , Endocrine Disruptors/toxicity , Rats , Estrus/drug effects , Luteinizing Hormone/blood , Fructose/toxicity , Fructose/analogs & derivatives , Pituitary Gland/drug effects , Pituitary Gland/metabolism , Progesterone/blood , Follicle Stimulating Hormone/blood , Gonadal Steroid Hormones/blood , Estradiol/blood , Ovary/drug effects , Ovary/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL