scholarly journals Clinical Models to Compare the Safety and Efficacy of Inhaled Corticosteroids in Patients with Asthma

2003 ◽  
Vol 10 (1) ◽  
pp. 27-34 ◽  
Author(s):  
Krishnan Parameswaran ◽  
Richard Leigh ◽  
Paul M O'Byrne ◽  
Margaret M Kelly ◽  
Charlie H Goldsmith ◽  
...  
Keyword(s):  
Dose Response ◽  
Inhaled Corticosteroids ◽  
Adenosine Monophosphate ◽  
Relative Potency ◽  
Pharmaceutical Equivalence ◽  
Inhaled Steroids ◽  
Advantages And Disadvantages ◽  
Flat Dose ◽  
Clinical Models ◽  
Airway Responses

There is no consensus on the methods to compare the clinical efficacy of different inhaled corticosteroids. A comparison needs to be made in terms of relative potency, and studies should include two-, or preferably, three-dose comparisons. A number of clinical models and outcomes are available; they have their relative advantages and disadvantages. While measurements of symptoms and spirometry are easy and readily available, they show a flat dose-response relationship. Measurements of bronchial hyper-responsiveness to exercise and adenosine monophosphate, allergen-induced airway responses, and measurements of inflammation in sputum and exhaled air show steep dose-response relationships, particularly to low doses of inhaled steroids. An uncontrolled asthma model followed by stabilization with a short course of additional steroid, with measurements of airway responsiveness and airway inflammation, in a crossover study seems more promising than the other models. Drug deposition studies and mathematical modelling of drug pharmacokinetics in the airway may provide complementary information to clinical drug relative potency studies. Fine particle dose and emitted doses, rather than the nominal dose, should be considered in the estimation of clinical and systemic effects, respectively. When a second entry (generic) drug is being evaluated in comparison with the innovator drug (same compound and same device), it may be appropriate to consider accepting a generic as bioequivalent if it satisfies pharmaceutical equivalence.

Eosinophilic bronchitis in asthma: A model for establishing dose-response and relative potency of inhaled corticosteroids

2006 ◽  
Vol 117 (5) ◽  
pp. 989-994 ◽  
Author(s):  
Margaret M. Kelly ◽  
Richard Leigh ◽  
Lata Jayaram ◽  
Charlie H. Goldsmith ◽  
Krishnan Parameswaran ◽  
...  
Keyword(s):  
Dose Response ◽  
Inhaled Corticosteroids ◽  
Relative Potency ◽  
Eosinophilic Bronchitis

ANTI-OVULATORY ACTIVITY OF STEROIDS ADMINISTERED BY GAVAGE IN THE ADULT OESTRUS RABBIT

1963 ◽  
Vol 42 (2_Suppl) ◽  
pp. S17-S30
Author(s):  
Fred A. Kind ◽  
Ralph I. Dorfman
Keyword(s):  
Dose Response ◽  
Active Compound ◽  
Subcutaneous Injection ◽  
Response Curve ◽  
Parent Compound ◽  
Dose Response Curve ◽  
Relative Potency ◽  
Reference Standard ◽  
Highly Active ◽  
Dose Levels

ABSTRACT Thirty-seven steroids have been studied as orally effective inhibitors of ovulation in the mated oestrus rabbit. Norethisterone served as the reference standard and a dose response curve was established between the 0.31 and 1.25 mg dose levels. Nine highly active anti-ovulatory compounds are described listed in a decreasing order of potency with norethisterone having the arbitrary value of one: 6-chloro-Δ6-dehydro-17α-acetoxyprogesterone (35), 6α-methyl-Δ1-dehydro-17α-acetoxyprogesterone (≥ 10), 6-fluoro-Δ6-dehydro-17α-acetoxyprogesterone(9), 6-methyl-Δ6-dehydro-17α-acetoxyprogesterone (5), Δ6-dehydro-17α-acetoxyprogesterone (≥ 3), 6α-methyl-17α-acetoxyprogesterone (2.6), 6-chloro-Δ1,6-bisdehydro-17α-acetoxyprogesterone (≥ 2), 2-hydroxymethyl-17α-methyl-17β-hydroxyandrostan-3-one (≥ 2), and 6α-fluoro-16α-methyl-17α-acetoxyprogesterone (≥ 1.25). The anti-ovulatory activity of a compound was not related necessarily to the progestational activity of a compound nor to the anti-gonadotrophic activity as measured in parabiotic rats. 6-Chloro-Δ60dehydro-17-acetoxyprogesterone was as effective by gavage as previously shown by subcutaneous injection. 2-Hydroxymethyl-17α-methyl-17β-hydroxyandrostan-3-one was at least 2.5 times more active by gavage than by injection. While 17α-acetoxyprogesterone was a very weak anti-ovulatory steroid, modifications of the structure by addition of methyl or halogen at the 6α position with or without unsaturation greatly increased the activity. 6-Chloro-Δ6-dehydro-27α-acetoxyprogesterone was the most active compound in this series showing a relative potency of 3500 times that of the parent compound 17α-acetoxyprogesterone.

A Random-allocation Graded Dose–Response Study of Norepinephrine and Phenylephrine for Treating Hypotension during Spinal Anesthesia for Cesarean Delivery

2017 ◽  
Vol 127 (6) ◽  
pp. 934-941 ◽  
Author(s):  
Warwick D. Ngan Kee
Keyword(s):  
Blood Pressure ◽  
Spinal Anesthesia ◽  
Cesarean Delivery ◽  
Dose Response ◽  
Relative Potency ◽  
First Episode ◽  
Response Analysis ◽  
Random Allocation ◽  
Dose Response Study ◽  
Different Doses

Abstract Background Norepinephrine has been investigated as a potential alterative to phenylephrine for maintaining blood pressure during spinal anesthesia for cesarean delivery with the advantage of less depression of maternal heart rate and cardiac output. However, the relative potencies of these two vasopressors have not been fully determined in this context. Methods In a random-allocation, graded dose–response study, 180 healthy patients undergoing spinal anesthesia for elective cesarean delivery received a single bolus of norepinephrine in one of six different doses ranging from 4 to 12 µg or phenylephrine in one of six different doses ranging from 60 to 200 µg to treat the first episode of hypotension. The magnitude of response was measured as the percentage of full restoration of systolic blood pressure to the baseline value. Dose–response analysis was performed using nonlinear regression to derive four-parameter logistic dose–response curves, which were compared to determine relative potency. Results Data were analyzed for 180 patients. The estimated ED50 values (dose giving a 50% response) were norepinephrine 10 µg (95% CI, 6 to 17 µg) and phenylephrine 137 µg (95% CI, 79 to 236 µg). The estimated relative potency ratio for the two drugs was 13.1 µg (95% CI, 10.4 to 15.8 µg). Conclusions Comparative dose–response analysis was completed for norepinephrine and phenylephrine given as a bolus to treat the first episode of hypotension in patients undergoing spinal anesthesia for cesarean delivery. The estimated dose equivalent to phenylephrine 100 µg was norepinephrine 8 µg (95% CI, 6 to 10 µg). These results may be useful to inform the design of future comparative studies.

scholarly journals Severe Oro-laryngeal Thrush Following Excessive Use of Steroid Inhaler

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Marina MB ◽  
Ramli R ◽  
Primuharsa Putra SHA
Keyword(s):  
Side Effects ◽  
Muscle Power ◽  
Inhaled Corticosteroids ◽  
Fungal Infections ◽  
Complete Recovery ◽  
Asthmatic Patients ◽  
Inhaled Steroids ◽  
Laryngeal Mucosa ◽  
Loss Of Appetite ◽  
Local Side

Introduction: Inhaled steroids such as fluticasone propionate and beclomethasone dipropionate play an important role in the treatment of bronchial asthma. Its usage facilitates disease control in asthmatic patients, resulting in improved quality of life. Because of its benefit, the inhaled steroid is used extensively, at higher doses and for longer duration. However, the localized effects of inhaled corticosteroids on oral/laryngeal mucosa, such as fungal infections can be problematic. Case Report: We report a case of oropharyngeal and laryngeal candidiasis following a long period and high doses of inhaled steroid in a 42-year-old male. He presented with a complaint of increasing tiredness, phlegm, intermittent wheezing and hoarseness for 2-3 months. There was no weight loss or loss of appetite. He has been using inhaled steroids and long acting bronchodilators in increasing doses for his claimed ‘wheezing’ despite the negative history of asthma. The inhaled steroids were fluticasone dipropionate at doses of 500-100 mcg daily for 2-3 months. Results: Examination revealed widespread oral thrush involving the oral cavity, oropharynx and larynx. There was no cushingoid habitus. His muscle power was of 5/5 bilaterally and his lungs were clear. Lung function and chest film were also normal. The steroid was stopped immediately and flucanozole and nystatin syrup were prescribed. The patient made an uneventful and complete recovery. Conclusion: We conclude that patients on inhaled corticosteroids should be monitored for local side effects. Physicians should be aware not only of the systemic but also of the local side effects of inhaled corticosteroids. Patients may increase doses without the knowledge of their physicians and subsequently suffer the adverse effects either local or systemic.

Inhaled corticosteroids in children with persistent asthma: dose-response effects on growth

2014 ◽  
Author(s):  
Aniela I Pruteanu ◽  
Bhupendrasinh F Chauhan ◽  
Linjie Zhang ◽  
Sílvio OM Prietsch ◽  
Francine M Ducharme
Keyword(s):  
Dose Response ◽  
Inhaled Corticosteroids ◽  
Persistent Asthma

Postoperative Inhaled Steroids Following Glottic Airway Surgery Reduces Granulation Tissue Formation

2021 ◽  
pp. 000348942110658
Author(s):  
Alison N. Hollis ◽  
Ameer Ghodke ◽  
Douglas Farquhar ◽  
Robert A. Buckmire ◽  
Rupali N. Shah
Keyword(s):  
Granulation Tissue ◽  
Laser Surgery ◽  
Vocal Fold ◽  
Inhaled Corticosteroids ◽  
Surgical Removal ◽  
Tissue Formation ◽  
Granulation Tissue Formation ◽  
Inhaled Steroids ◽  
Transoral Laser Surgery ◽  
Airway Surgery

Objectives: Transoral laser surgery for glottic stenosis (transverse cordotomy and anteromedial arytenoidectomy (TCAMA)) is often complicated by granulation tissue (GT) formation. GT can cause dyspnea and may require surgical removal to alleviate airway obstruction. Inhaled corticosteroids (ICS) have been shown to reduce benign vocal fold granulomas, however its use to prevent GT formation has not been described. We aimed to analyze the effect of immediate postoperative ICS on GT formation in patients undergoing transoral laser surgery for glottic stenosis. Methods: A retrospective analysis of patients that had transoral laser surgery for glottic stenosis from 2000 to 2019 was conducted. Surgical instances were grouped into those that received postoperative ICS and those that did not. Demographics, diagnosis, comorbidities, intraoperative adjuvant therapy, and perioperative medications were collected. Differences in GT formation and need for surgical removal were compared between groups. A multivariate exact logistic regression model was performed. Results: Forty-four patients were included; 16 required 2 glottic airway surgeries (60 surgical instances). Of the 23 instances where patients received immediate postoperative ICS, 0 patients developed GT; and of the 37 instances that did not receive postoperative ICS, 15 (40.5%) developed GT ( P < .0001). Eight (53.3%) of these cases returned to the OR for GT removal. ICS use was solely associated with the absence of GT formation ( P = .042) in the multivariate analysis. Conclusions: Immediate postoperative use of ICS seems to be a safe and effective method to prevent granulation tissue formation and subsequent surgery in patients following transoral laser airway surgery for glottic stenosis.

Evaluation of the clinical relevance and limitations of current pre-clinical models of peripheral artery disease

2015 ◽  
Vol 130 (3) ◽  
pp. 127-150 ◽  
Author(s):  
Smriti Murali Krishna ◽  
Safraz Mohamed Omer ◽  
Jonathan Golledge
Keyword(s):  
Physical Activity ◽  
Risk Factors ◽  
Animal Models ◽  
Peripheral Artery Disease ◽  
Clinical Relevance ◽  
Peripheral Artery ◽  
Advantages And Disadvantages ◽  
Clinical Models ◽  
Artery Disease

Peripheral artery disease (PAD) has recognized treatment deficiencies requiring the discovery of novel interventions. This article describes current animal models of PAD and discusses their advantages and disadvantages. There is a need for models which more directly simulate the characteristics of human PAD, such as acute-on-chronic presentation, presence of established risk factors and impairment of physical activity.

scholarly journals The Airways’ Mechanical Stress in Lung Disease: Implications for COPD Pathophysiology and Treatment Evaluation

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Pierachille Santus ◽  
Matteo Pecchiari ◽  
Francesco Tursi ◽  
Vincenzo Valenti ◽  
Marina Saad ◽  
...  
Keyword(s):  
Mechanical Stress ◽  
Inhaled Corticosteroids ◽  
Treatment Strategies ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Underlying Mechanism ◽  
Current Evidence ◽  
Chronic Obstructive ◽  
Copd Exacerbations ◽  
Long Acting

The airway epithelium stretches and relaxes during the normal respiratory cycle, and hyperventilation exaggerates this effect, resulting in changes in lung physiology. In fact, stretching of the airways influences lung function and the secretion of airway mediators, which in turn may cause a potentially injurious inflammatory response. This aim of the present narrative review was to illustrate the current evidence on the importance of mechanical stress in the pathophysiology of lung diseases with a particular focus on chronic obstructive pulmonary disease (COPD) and to discuss how this may influence pharmacological treatment strategies. Overall, treatment selection should be tailored to counterpart the effects of mechanical stress, which influences inflammation both in asthma and COPD. The most suitable treatment approach between a long-acting β2-agonists/long-acting antimuscarinic-agonist (LABA/LAMA) alone or with the addition of inhaled corticosteroids should be determined based on the underlying mechanism of inflammation. Noteworthy, the anti-inflammatory effects of the glycopyrronium/indacaterol combination on hyperinflation and mucociliary clearance may decrease the rate of COPD exacerbations, and it may synergistically improve bronchodilation with a double action on both the cyclic adenosine monophosphate (cAMP) and the acetylcholine pathways.

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