scholarly journals Topiramate is more effective than acetazolamide at lowering intracranial pressure

Cephalalgia ◽  
2018 ◽  
Vol 39 (2) ◽  
pp. 209-218 ◽  
Author(s):  
William J Scotton ◽  
Hannah F Botfield ◽  
Connar SJ Westgate ◽  
James L Mitchell ◽  
Andreas Yiangou ◽  
...  
Keyword(s):  
Intracranial Pressure ◽  
Oral Administration ◽  
Intracranial Hypertension ◽  
Idiopathic Intracranial Hypertension ◽  
Subcutaneous Administration ◽  
Female Rats ◽  
In Vivo Studies ◽  
Human Dose ◽  
High Doses

Background The management of idiopathic intracranial hypertension focuses on reducing intracranial pressure to preserve vision and reduce headaches. There is sparse evidence to support the use of some of the drugs commonly used to manage idiopathic intracranial hypertension, therefore we propose to evaluate the efficacy of these drugs at lowering intracranial pressure in healthy rats. Methods We measured intracranial pressure in female rats before and after subcutaneous administration of acetazolamide, topiramate, furosemide, amiloride and octreotide at clinical doses (equivalent to a single human dose) and high doses (equivalent to a human daily dose). In addition, we measured intracranial pressure after oral administration of acetazolamide and topiramate. Results At clinical and high doses, subcutaneous administration of topiramate lowered intracranial pressure by 32% ( p = 0.0009) and 21% ( p = 0.015) respectively. There was no significant reduction in intracranial pressure noted with acetazolamide, furosemide, amiloride or octreotide at any dose. Oral administration of topiramate significantly lowered intracranial pressure by 22% ( p = 0.018), compared to 5% reduction with acetazolamide ( p = >0.999). Conclusion Our in vivo studies demonstrated that both subcutaneous and oral administration of topiramate significantly lowers intracranial pressure. Other drugs tested, including acetazolamide, did not significantly reduce intracranial pressure. Future clinical trials evaluating the efficacy and side effects of topiramate in idiopathic intracranial hypertension patients would be of interest.

scholarly journals Characterization of PCL and Chitosan Nanoparticles as Carriers of Enoxaparin and Its Antithrombotic Effect in Animal Models of Venous Thrombosis

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Lucas Bessa Prado ◽  
Stephany Cares Huber ◽  
Aline Barnabé ◽  
Fernanda Dutra Santiago Bassora ◽  
Devanira Souza Paixão ◽  
...  
Keyword(s):  
Oral Administration ◽  
Encapsulation Efficiency ◽  
Anticoagulant Activity ◽  
Chitosan Nanoparticles ◽  
Subcutaneous Administration ◽  
Double Emulsion ◽  
In Vivo Studies ◽  
Control Group ◽  
Antithrombotic Effect

This study was based on the preparation, characterization, and animal in vivo experiments performed to evaluate nanoparticles of poly(ɛ-caprolactone) (PCL) and chitosan as carriers of enoxaparin. The nanoparticles were characterized and presented satisfactory results in terms of size, polydispersity, and encapsulation efficiency. Anticoagulant activity of the nanoparticles was maintained for 14 hours when the administration was subcutaneous; however no activity was observed after oral administration. There was a significant reduction in thrombus size, in vivo, for both free and encapsulated enoxaparin in comparison with the control group after subcutaneous administration. Oral administration results however were indifferent. In conclusion, the double emulsion method w/o/w was efficient for enoxaparin encapsulation, producing spherical nanoparticles with high encapsulation efficiency. For in vivo studies, the encapsulated enoxaparin showed a sustained anticoagulant activity for a higher period of time compared to free enoxaparin, with an antithrombotic effect when administered subcutaneously.

scholarly journals Preclinical update on regulation of intracranial pressure in relation to idiopathic intracranial hypertension

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Sajedeh Eftekhari ◽  
Connar Stanley James Westgate ◽  
Maria Schmidt Uldall ◽  
Rigmor Hoejland Jensen
Keyword(s):  
Intracranial Pressure ◽  
Intracranial Hypertension ◽  
Idiopathic Intracranial Hypertension ◽  
Drug Targets ◽  
Molecular Mechanisms ◽  
Special Focus ◽  
Icp Monitoring ◽  
Preclinical Research ◽  
New Drug

Abstract Background Elevated intracranial pressure (ICP) is observed in association with a range of brain disorders. One of these challenging disorders is idiopathic intracranial hypertension (IIH), characterized by raised ICP of unknown cause with significant morbidity and limited therapeutic options. In this review, special focus is put on the preclinical research performed in order to understand the pathophysiology behind ICP regulation and IIH. This includes cerebrospinal fluid dynamics, molecular mechanisms underlying disturbances in brain fluids leading to elevated ICP, role of obesity in IIH, development of an IIH model and ICP measurements in rodents. The review also discusses existing and new drug targets for IIH that have been evaluated in vivo. Conclusions ICP monitoring in rodents is challenging and different methods have been applied. Some of these methods are invasive, depend on use of anesthesia and only allow short-term monitoring. Long-term ICP recordings are needed to study IIH but existing methods are hampered by several limitations. As obesity is one of the most common risk factors for IIH, a rodent obese model has been developed that mimics some key aspects of IIH. The most commonly used drugs for IIH have been evaluated in vivo for their efficacy at lowering ICP in the existing animal models. These studies suggest these drugs, including acetazolamide, might have limited or no reducing effect on ICP. Two drug targets that can impact ICP in healthy rodents are topiramate and a glucagon-like peptide-1 receptor (GLP-1R) agonist. However, it remains to evaluate their effect in an IIH model with more precise and valid ICP monitoring system. Therefore, continued evaluation in the preclinical research with refined tools is of great importance to further understand the pathophysiology behind disorders with raised ICP and to explore new drug targets.

scholarly journals Evaluation of cerebrovascular hemodynamics in patients with idiopathic intracranial hypertension using transcranial Doppler

2020 ◽  
Vol 56 (1) ◽  
Author(s):  
Mahmoud M. Allam ◽  
Hatem A. Almasry ◽  
Sandra M. Ahmed ◽  
Youssuf G. Taha ◽  
Mohammed I. Oraby
Keyword(s):  
Intracranial Pressure ◽  
Intracranial Hypertension ◽  
Lumbar Puncture ◽  
Transcranial Doppler ◽  
Idiopathic Intracranial Hypertension ◽  
Pulsatility Index ◽  
Research Work ◽  
Increased Intracranial Pressure ◽  
Significant Relation ◽  
Before And After

Abstract Background Idiopathic intracranial hypertension (IIH) is a disorder of increased intracranial pressure without a clear cause and can have serious visual effects. Previous research work suggests that transcranial Doppler measurements of pulsatility index correlate accurately with elevated intracranial pressure. Objective To assess the cerebrovascular hemodynamic changes in patients with IIH using transcranial Doppler before and after lumbar puncture and CSF withdrawal. Methods An interventional study conducted on 40 patients (31 females and 9 males) fulfilling the modified Dandy criteria for diagnosis of idiopathic intracranial hypertension, MRI brain, and MRV was done to the patients. Lumbar puncture was done for all included patients to measure intracranial pressure and CSF withdrawal. Transcranial Doppler was performed for all included before and after lumbar puncture and CSF withdrawal and the following parameters were measured: peak systolic velocity (PSV), end diastolic velocity (EDV), resistivity index (RI), and pulsatility index (PI). Results Significant relation was found between grades of papilledema and PSV, RI, and PI (p value 0.012, 0.025, 0.016) but no significant relation was found between grades of papilledema and EDV (0.102). Significant changes occurred in parameters of TCD pre- and post-CSF withdrawal including PSV, EDV, and PI (p value 0.001, 0.015, 0.019) denoting a significant change in cerebral hemodynamics after CSF withdrawal which denotes a decrease in intracranial pressure. Conclusion Increased intracranial pressure significantly affects cerebral blood flow. A normalization of transcranial Doppler parameters occurs following lowering of intracranial pressure through lumbar puncture and CSF withdrawal.

scholarly journals 11β-Hydroxysteroid dehydrogenase type 1 inhibition in idiopathic intracranial hypertension: a double-blind randomized controlled trial

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Keira Markey ◽  
James Mitchell ◽  
Hannah Botfield ◽  
Ryan S Ottridge ◽  
Tim Matthews ◽  
...  
Keyword(s):  
Intracranial Hypertension ◽  
Lumbar Puncture ◽  
Idiopathic Intracranial Hypertension ◽  
Controlled Trial ◽  
Hydroxysteroid Dehydrogenase ◽  
Opening Pressure ◽  
Double Blind ◽  
Randomized Controlled

Abstract Treatment options for idiopathic intracranial hypertension are limited. The enzyme 11β-hydroxysteroid dehydrogenase type 1 has been implicated in regulating cerebrospinal fluid secretion, and its activity is associated with alterations in intracranial pressure in idiopathic intracranial hypertension. We assessed therapeutic efficacy, safety and tolerability and investigated indicators of in vivo efficacy of the 11β-hydroxysteroid dehydrogenase type 1 inhibitor AZD4017 compared with placebo in idiopathic intracranial hypertension. A multicenter, UK, 16-week phase II randomized, double-blind, placebo-controlled trial of 12-week treatment with AZD4017 or placebo was conducted. Women aged 18–55 years with active idiopathic intracranial hypertension (>25 cmH2O lumbar puncture opening pressure and active papilledema) were included. Participants received 400 mg of oral AZD4017 twice daily compared with matching placebo over 12 weeks. The outcome measures were initial efficacy, safety and tolerability. The primary clinical outcome was lumbar puncture opening pressure at 12 weeks analysed by intention-to-treat. Secondary clinical outcomes were symptoms, visual function, papilledema, headache and anthropometric measures. In vivo efficacy was evaluated in the central nervous system and systemically. A total of 31 subjects [mean age 31.2 (SD = 6.9) years and body mass index 39.2 (SD = 12.6) kg/m2] were randomized to AZD4017 (n = 17) or placebo (n = 14). At 12 weeks, lumbar puncture pressure was lower in the AZD4017 group (29.7 cmH2O) compared with placebo (31.3 cmH2O), but the difference between groups was not statistically significant (mean difference: −2.8, 95% confidence interval: −7.1 to 1.5; P = 0.2). An exploratory analysis assessing mean change in lumbar puncture pressure within each group found a significant decrease in the AZD4017 group [mean change: −4.3 cmH2O (SD = 5.7); P = 0.009] but not in the placebo group [mean change: −0.3 cmH2O (SD = 5.9); P = 0.8]. AZD4017 was safe, with no withdrawals related to adverse effects. Nine transient drug-related adverse events were reported. One serious adverse event occurred in the placebo group (deterioration requiring shunt surgery). In vivo biomarkers of 11β-hydroxysteroid dehydrogenase type 1 activity (urinary glucocorticoid metabolites, hepatic prednisolone generation, serum and cerebrospinal fluid cortisol:cortisone ratios) demonstrated significant enzyme inhibition with the reduction in serum cortisol:cortisone ratio correlating significantly with reduction in lumbar puncture pressure (P = 0.005, R = 0.70). This is the first phase II randomized controlled trial in idiopathic intracranial hypertension evaluating a novel therapeutic target. AZD4017 was safe and well tolerated and inhibited 11β-hydroxysteroid dehydrogenase type 1 activity in vivo. Reduction in serum cortisol:cortisone correlated with decreased intracranial pressure. Possible clinical benefits were noted in this small cohort. A longer, larger study would now be of interest.

Intracranial hypertension and papilloedema as a complication to low antiretroviral therapy adherence in a man living with chronic HIV

2021 ◽  
Vol 14 (3) ◽  
pp. e237504
Author(s):  
Rosa Maja Møhring Gynthersen ◽  
Helene Mens ◽  
Marianne Wegener ◽  
Neval Ete Wareham
Keyword(s):  
Antiretroviral Therapy ◽  
Intracranial Pressure ◽  
Intracranial Hypertension ◽  
Idiopathic Intracranial Hypertension ◽  
Ventricular Volume ◽  
Art Adherence ◽  
Hiv Viral Load ◽  
Blurred Vision ◽  
Antiretroviral Therapy Adherence ◽  
Acute Retroviral Syndrome

We describe a 61-year-old man living with HIV on antiretroviral therapy (ART), who presented with headache, dizziness and blurred vision. Latest CD4+ cell count 3 months prior to admission was 570×106 cells/mL and HIV viral load <20 copies/mL. The patient was diagnosed with cerebrospinal fluid (CSF) lymphocytic pleocytosis, raised intracranial pressure and papilloedema. Neuroimaging showed normal ventricular volume and no mass lesions, suggesting (1) neuroinfection (2) idiopathic intracranial hypertension or (3) retroviral rebound syndrome (RRS) as possible causes. Neuroinfection was ruled out and idiopathic intracranial hypertension seemed unlikely. Elevated plasma HIV RNA level was detected consistent with reduced ART adherence prior to admission. RRS is a virological rebound after ART interruption, which can mimic the acute retroviral syndrome of acute primary infection. To the best of our knowledge, we describe the second case of RRS presenting as CSF lymphocytic pleocytosis and elevated intracranial pressure after low ART adherence.

The Potentially Modifiable Risk Factor in Idiopathic Intracranial Hypertension: Body Weight

2021 ◽  
pp. 10.1212/CPJ.0000000000001063
Author(s):  
Susan P Mollan ◽  
Abd A Tahrani ◽  
Alexandra J Sinclair
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Risk Factor ◽  
Intracranial Pressure ◽  
Intracranial Hypertension ◽  
Treatment Strategy ◽  
Idiopathic Intracranial Hypertension ◽  
Potential Treatment ◽  
Distal Small Intestine

AbstractPurpose of review:Idiopathic intracranial hypertension (IIH) prevalence increased in conjunction with rising obesity rates. Here, we highlight the importance of weigh management in IIH, and introduce glucagon-like peptide 1 (GLP-1) receptor agonists (RA) as potential treatment strategy for IIH.Recent findings:Weight gain is a risk factor for IIH; and weight loss (via any treatment strategy) plays a key role in IIH management. GLP-1 is an incretin secreted by the distal small intestine in response to a meal. GLP-1 RA have been shown to improve glycaemic control (no. hypoglycaemia) and lower body weight in patients with and without type 2 diabetes. The choroid plexus has been found to express GLP-1 receptors and treatment with a GLP-1 RA significantly reduces cerebrospinal fluid secretion in vitro and intracranial pressure in rodents.Summary:New research evaluating the pathophysiology of IIH supports GLP-1 RA as a potential treatment for IIH via weight loss dependant and independent mechanism to directly reduce intracranial pressure.

scholarly journals Design and Characterization of Combinational Domperidone-Famotidine Floating Drug Delivery System - In vitro and In vivo studies

2021 ◽  
Vol 62 (2) ◽  
pp. 144-162
Author(s):  
Mounika Chidurala ◽  
Raveendra Reddy J
Keyword(s):  
Drug Release ◽  
Oral Administration ◽  
Quality By Design ◽  
Release Kinetics ◽  
Cost Effective ◽  
Fickian Diffusion ◽  
In Vivo Studies ◽  
Pharmacokinetic Studies

Introduction: The drawbacks assosiated with oral administration of drugscan be controlled or minimized by gastro retentive formulations that remain buoyant within the stomach for an extended time by providing prolonged gastric retention and releasethe drug in an exceedingly extended manner thereby improving bioavailability. The current research was to develop and optimize Domperidone and Famotidine floating tablets with extended release by Quality by Design approach. Method: Based on QTPP (Quality Target Product Profile), CQAs (Critical Quality Attributes)wereidentified. Risk analysis by the evaluation of formulation and process parameters showed that optimizing the levels of polymers could reduce high risk to achieve the target profile. A 23factor experimental design with midpoints was selected for statistical analysis and optimization. Results: HPMC K100 and Carbopol 934P had a positive effect while ethyl cellulose demonstrated a negative effect on the selected responses. Drug release kinetics followed the first-order release with Higuchi diffusion and Fickian diffusion. Optimized formula satisfying all the required parameters was selected and evaluated. The predicted response values were in close agreement with experimental response values. Abdominal X-ray imaging after oral administration of the tablets on a healthy rabbit’s stomach confirmed the extended floating behavior with shorter lag time. In vivo, pharmacokinetic studies in rabbits revealed that the optimized formulation exhibited prolonged drug release with enhanced Cmax, tmax, AUCo-t, and t1/2 of an optimized product when compared to the marketed product. Conclusions: It has been concluded that the application of Quality by Design in the formulation and optimization reduced the number of trials to produce a cost-effective formula.

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