pulmicort and flunisolide

Bronchopulmonary dysplasia (BPD), defined as oxygen dependence at 36 weeks postmenstrual age (PMA), remains an important complication of prematurity. Pulmonary inflammation plays a central role in the pathogenesis of BPD. Attenuating pulmonary inflammation with postnatal systemic corticosteroids reduces the incidence of BPD in preterm infants but may be associated with an increased risk of adverse neurodevelopmental outcomes. Local administration of corticosteroids via inhalation might be an effective and safe alternative.. To determine if administration of inhalation corticosteroids after the first week of life until 36 weeks PMA to preterm infants at high risk of developing BPD is effective and safe in reducing the incidence of death and BPD as separate or combined outcomes.. We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2017, Issue 4), MEDLINE via PubMed (1966 to 19 May 2017), Embase (1980 to 19 May 2017), and CINAHL (1982 to 19 May 2017). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials.. We included randomised controlled trials comparing inhalation corticosteroids, started ≥ 7 days postnatal age (PNA) but before 36 weeks PMA, to placebo in ventilated and non-ventilated infants at risk of BPD. We excluded trials investigating systemic corticosteroids versus inhalation corticosteroids.. We collected data on participant characteristics, trial methodology, and inhalation regimens. The primary outcome was death or BPD at 36 weeks PMA. Secondary outcomes were the combined outcome death or BPD at 28 days PNA, the seperate outcomes of death and BPD at both 28 days PNA, and at 36 weeks PMA, and short-term respiratory outcomes, such as failure to extubate; total days of mechanical ventilation and oxygen use; and the need for systemic corticosteroids. We contacted the original trialists to verify the validity of extracted data and to provide missing data. We analysed all data using Review Manager 5. When possible, we performed meta-analysis using typical risk ratio (RR) for dichotomous outcomes and weighted mean difference (WMD) for continuous outcomes along with their 95% confidence intervals (CI). We analysed ventilated and non-ventilated participants separately.We used the GRADE approach to assess the quality of the evidence.. We included eight trials randomising 232 preterm infants in this review. Inhalation corticosteroids did not reduce the separate or combined outcomes of death or BPD. The meta-analyses of the studies showed a reduced risk in favor of inhalation steroids regarding failure to extubate at seven days (typical RR (TRR) 0.80, 95% CI 0.66 to 0.98; 5 studies, 79 infants) and at the latest reported time point after treatment onset (TRR 0.60, 95% CI 0.45 to 0.80; 6 studies, 90 infants). However, both analyses showed increased statistical heterogeneity (I. Based on the results of the currently available evidence, inhalation corticosteroids initiated at ≥ 7 days of life for preterm infants at high risk of developing BPD cannot be recommended at this point in time. More and larger randomised, placebo-controlled trials are needed to establish the efficacy and safety of inhalation corticosteroids.

Topics: Administration, Inhalation; Anti-Inflammatory Agents; Beclomethasone; Bronchopulmonary Dysplasia; Budesonide; Dexamethasone; Fluocinolone Acetonide; Fluticasone; Glucocorticoids; Humans; Infant, Newborn; Infant, Premature; Pneumonia; Randomized Controlled Trials as Topic

Treatment guidelines for asthma recommend inhaled corticosteroids (ICS) as first-line therapy for children with persistent asthma. Although ICS treatment is generally considered safe in children, the potential systemic adverse effects related to regular use of these drugs have been and continue to be a matter of concern, especially the effects on linear growth.. To assess the impact of ICS on the linear growth of children with persistent asthma and to explore potential effect modifiers such as characteristics of available treatments (molecule, dose, length of exposure, inhalation device) and of treated children (age, disease severity, compliance with treatment).. We searched the Cochrane Airways Group Specialised Register of trials (CAGR), which is derived from systematic searches of bibliographic databases including CENTRAL, MEDLINE, EMBASE, CINAHL, AMED and PsycINFO; we handsearched respiratory journals and meeting abstracts. We also conducted a search of ClinicalTrials.gov and manufacturers' clinical trial databases to look for potential relevant unpublished studies. The literature search was conducted in January 2014.. Parallel-group randomised controlled trials comparing daily use of ICS, delivered by any type of inhalation device for at least three months, versus placebo or non-steroidal drugs in children up to 18 years of age with persistent asthma.. Two review authors independently performed study selection, data extraction and assessment of risk of bias in included studies. We conducted meta-analyses using the Cochrane statistical package RevMan 5.2 and Stata version 11.0. We used the random-effects model for meta-analyses. We used mean differences (MDs) and 95% CIs as the metrics for treatment effects. A negative value for MD indicates that ICS have suppressive effects on linear growth compared with controls. We performed a priori planned subgroup analyses to explore potential effect modifiers, such as ICS molecule, daily dose, inhalation device and age of the treated child.. We included 25 trials involving 8471 (5128 ICS-treated and 3343 control) children with mild to moderate persistent asthma. Six molecules (beclomethasone dipropionate, budesonide, ciclesonide, flunisolide, fluticasone propionate and mometasone furoate) [corrected] given at low or medium daily doses were used during a period of three months to four to six years. Most trials were blinded and over half of the trials had drop out rates of over 20%.Compared with placebo or non-steroidal drugs, ICS produced a statistically significant reduction in linear growth velocity (14 trials with 5717 participants, MD -0.48 cm/y, 95% CI -0.65 to -0.30, moderate quality evidence) and in the change from baseline in height (15 trials with 3275 participants; MD -0.61 cm/y, 95% CI -0.83 to -0.38, moderate quality evidence) during a one-year treatment period.Subgroup analysis showed a statistically significant group difference between six molecules in the mean reduction of linear growth velocity during one-year treatment (Chi² = 26.1, degrees of freedom (df) = 5, P value < 0.0001). The group difference persisted even when analysis was restricted to the trials using doses equivalent to 200 μg/d hydrofluoroalkane (HFA)-beclomethasone. Subgroup analyses did not show a statistically significant impact of daily dose (low vs medium), inhalation device or participant age on the magnitude of ICS-induced suppression of linear growth velocity during a one-year treatment period. However, head-to-head comparisons are needed to assess the effects of different drug molecules, dose, inhalation device or patient age. No statistically significant difference in linear growth velocity was found between participants treated with ICS and controls during the second year of treatment (five trials with 3174 participants; MD -0.19 cm/y, 95% CI -0.48 to 0.11, P value 0.22). Of two trials that reported linear growth velocity in the third year of treatment, one trial involving 667 participants showed similar growth velocity between the budesonide and placebo groups (5.34 cm/y vs 5.34 cm/y), and another trial involving 1974 participants showed lower growth velocity in the budesonide group compared with the placebo group (MD -0.33 cm/y, 95% CI -0.52 to -0.14, P value 0.0005). Among four trials reporting data on linear growth after treatment cessation, three did not describe statistically significant catch-up growth in the ICS group two to four months after treatment cessation. One trial showed accelerated li. Regular use of ICS at low or medium daily doses is associated with a mean reduction of 0.48 cm/y in linear growth velocity and a 0.61-cm change from baseline in height during a one-year treatment period in children with mild to moderate persistent asthma. The effect size of ICS on linear growth velocity appears to be associated more strongly with the ICS molecule than with the device or dose (low to medium dose range). ICS-induced growth suppression seems to be maximal during the first year of therapy and less pronounced in subsequent years of treatment. However, additional studies are needed to better characterise the molecule dependency of growth suppression, particularly with newer molecules (mometasone, ciclesonide), to specify the respective role of molecule, daily dose, inhalation device and patient age on the effect size of ICS, and to define the growth suppression effect of ICS treatment over a period of several years in children with persistent asthma.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Budesonide; Child; Child, Preschool; Fluocinolone Acetonide; Fluticasone; Growth; Growth Disorders; Humans; Mometasone Furoate; Patient Dropouts; Pregnadienediols; Pregnenediones

Bronchopulmonary dysplasia (BPD), defined as oxygen dependence at 36 weeks postmenstrual age (PMA), remains an important complication of prematurity. Pulmonary inflammation plays a central role in the pathogenesis of BPD. Attenuating pulmonary inflammation with postnatal systemic corticosteroids reduces the incidence of BPD in preterm infants but may be associated with an increased risk of adverse neurodevelopmental outcomes. Local administration of corticosteroids via inhalation might be an effective and safe alternative.. To determine if administration of inhalation corticosteroids after the first week of life to preterm infants at high risk of developing BPD is effective and safe in reducing the incidence of death and BPD as separate or combined outcomes.. We identified randomised, controlled trials by searching the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), PubMed (from 1966), EMBASE (from 1974), CINAHL (from 1982), references from retrieved trials and handsearches of journals, all assessed to February 2012.. Randomised controlled trials comparing inhalation corticosteroids, started ≥ 7 days postnatal age (PNA) but before 36 weeks PMA, to placebo in ventilated and non-ventilated infants at risk of BPD were included. Trials investigating systemic corticosteroids versus inhalation corticosteroids were excluded.. Data on patient characteristics, trial methodology, and inhalation regimens were collected. The primary outcomes were death or BPD, or both, at 28 days PNA or 36 weeks PMA. Secondary outcomes were short-term respiratory outcomes, such as failure to extubate, total days of mechanical ventilation and oxygen use, and the need for systemic corticosteroids. The original trialists were contacted to verify the validity of extracted data and to provide missing data. All data were analysed using RevMan 5.0.24. When possible, meta-analysis was performed using typical risk ratio (TRR) for dichotomous outcomes and weighted mean difference (WMD) for continuous outcomes along with their 95% confidence intervals (CI). Ventilated and non-ventilated participants were analysed separately.. Eight trials randomising 232 preterm infants were included in this review. Inhalation corticosteroids did not reduce the separate or combined outcomes of death or BPD. Furthermore, inhalation steroids did not impact short-term respiratory outcomes such as failure to extubate and total duration of mechanical ventilation or oxygen dependency. There was a trend to a reduced use of systemic corticosteroids in favour of inhalation corticosteroids (TRR 0.51; 95% CI 0.26 to 1.00). There was a paucity of data on short-term and long-term adverse effects. These results should be interpreted with caution because the total number of randomised patients is relatively small and most trials differed considerably in patient characteristics, inhalation therapy and outcome definitions.. Based on the results of the currently available evidence, inhalation corticosteroids initiated at ≥ 7 days of life for preterm infants at high risk of developing BPD cannot be recommended at this point in time. More and larger randomised, placebo-controlled trials are needed to establish the efficacy and safety of inhalation corticosteroids.

Topics: Administration, Inhalation; Androstadienes; Anti-Inflammatory Agents; Beclomethasone; Bronchopulmonary Dysplasia; Budesonide; Dexamethasone; Fluocinolone Acetonide; Fluticasone; Glucocorticoids; Humans; Infant, Newborn; Infant, Premature; Pneumonia; Randomized Controlled Trials as Topic

The objective of this study was to analyse inter-and intra-country quantitative and qualitative differences in anti-asthmatic prescriptions to children and adolescents.. A literature search was performed in EMBASE and MEDLINE to identify pharmaco-epidemiological studies published from January 1, 2000 to December 31, 2008 in which anti-asthmatic prescription prevalence in out-hospital children was measured. A meta-analytic weighted average and 95% confidence intervals of prescription prevalences were calculated using a random-effect(s) model. Inter- and intra-country quantitative and, where possible, qualitative prescribing patterns were compared and assessed.. Twelve studies were identified (ten from Europe, one from Canada and one from the USA), but epidemiological indicators varied widely, and only eight were suitable for meta-analysis. The data from these studies revealed inter-country quantitative differences in prescription prevalences in the overall population

Topics: Acetates; Adolescent; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Budesonide; Canada; Child; Cromolyn Sodium; Cyclopropanes; Drug Prescriptions; Ethanolamines; Europe; Fluocinolone Acetonide; Fluticasone; Humans; Italy; Prevalence; Quinolines; Salmeterol Xinafoate; Sulfides; United States

The introduction of nasal glucocorticosteroids, 30 years ago, has been the most important therapeutic progress in rhinitis management since the introduction of the first generation of antihistamines. Our knowledge of the mode of action of glucocorticosteroids in the nose has improved as the airway mucous membrane of the nose is easily accessible for investigation. However, the exact mechanism behind the marked clinical effect remains unclear. Topical glucocorticosteroids are highly effective in diseases characterized by eosinophil-dominated inflammation (allergic rhinitis, nasal polyposis), but not in diseases characterized by neutrophil-dominated inflammation (common cold, infectious rhinosinusitis). Experience for 30 years and a long series of controlled studies have shown that the treatment is highly effective and that the side effects are few and benign. Intranasal glucocorticosteroids can therefore be considered as first-line treatment for allergic and non-allergic, non-infectious rhinitis and nasal polyps.

Topics: Administration, Topical; Androstadienes; Animals; Beclomethasone; Budesonide; Dexamethasone; Eosinophils; Fluocinolone Acetonide; Fluticasone; Glucocorticoids; Humans; Mometasone Furoate; Nasal Mucosa; Nasal Polyps; Pregnadienediols; Randomized Controlled Trials as Topic; Rhinitis; Treatment Outcome; Triamcinolone Acetonide

Topics: Administration, Intranasal; Androstadienes; Anti-Inflammatory Agents; Beclomethasone; Budesonide; Chronic Disease; Diagnosis, Differential; Drug Administration Schedule; Fluocinolone Acetonide; Fluticasone; Glucocorticoids; Humans; Nurse Practitioners; Nurse's Role; Patient Satisfaction; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Severity of Illness Index; Triamcinolone

We performed a systematic review of randomized, controlled trials to determine whether intranasal corticosteroids offered an advantage over topical antihistamines in the treatment of allergic rhinitis.. We searched for studies using MEDLINE, Embase, Cinahi, and Cochrane databases, pharmaceutical companies, and references of included trials.. Criteria for considering trials included: 1) published randomized controlled trials; 2) single- or double-blind studies; and 3) presence of one of the following clinical outcomes: nasal symptoms, eye symptoms, global symptoms evaluation of quality of life and side effects.. Nine studies including 648 subjects (mean age 30.4 years, range 13 to 73) with allergic rhinitis were selected. Intranasal corticosteroids produced significantly greater reduction of total nasal symptoms (standardized mean difference -0.36, 95% confidence interval -0.57 to -0.14), sneezing (-0.41, -0.57 to -0.24), rhinorrhea (-0.47, -0.64 to -0.29), itching (-0.38, -0.56 to -0.19), and nasal blockage (-0.86, -1.07 to -0.64) than did topical antihistamines. There was no significant difference between treatments for ocular symptoms (-0.07, -0.27 to 0.12). The effects on sneezing, rhinorrhea, itching, and ocular symptoms were significantly heterogeneous between studies. Other outcomes (total nasal symptom score and nasal blockage) were homogeneous between studies. Subgroup and sensitivity analysis suggested that most of the heterogeneity of outcomes could be explained on the basis of the methodologic quality of studies.. Intranasal corticosteroids produced greater relief of nasal symptoms than did topical antihistamines (topical H1 receptor antagonists). However, there was no difference in the relief of the ocular symptoms.

Topics: Administration, Intranasal; Administration, Topical; Adolescent; Adult; Aged; Androstadienes; Anti-Allergic Agents; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Beclomethasone; Budesonide; Fluocinolone Acetonide; Fluticasone; Glucocorticoids; Histamine H1 Antagonists; Humans; Middle Aged; Phthalazines; Piperidines; Randomized Controlled Trials as Topic; Rhinitis, Allergic, Seasonal; Treatment Outcome

Topical administration of corticosteroids can reduce the total dose of corticosteroid required to treat the patient and minimize side effects. This logic has led to the development of intranasal corticosteroids (INCS) for allergic and perennial rhinitis. The second generation of these compounds includes beclomethasone dipropionate, budesonide, flunisolide, fluticasone propionate, mometasone furoate, and triamcinolone acetonide. There is evidence that the INCS are effective in rhinitis; however, there is concern about the potential for these compounds to cause growth suppression. In one study, beclomethasone dipropionate significantly reduced growth in children; however, treatment of children with mometasone furoate nasal spray for 1 year showed no signs of growth suppression. It is evident that the differences among INCS lie in their pharmacokinetics. Structural differences among the various INCS influence their metabolism. The goal of INCS therapy is to have a high ratio of topical to systemic activity. The drug delivery device, absorption of the drug, and drug distribution all contribute to effective topical activity of an INCS. In addition, individual drug metabolism and elimination (half-life and drug clearance) also contribute to the therapeutic index of a drug. Overall, the second-generation INCS cause minimal systemic effects at recommended doses.

Topics: Absorption; Administration, Intranasal; Adrenal Cortex Hormones; Adult; Androstadienes; Anti-Allergic Agents; Anti-Inflammatory Agents; Beclomethasone; Budesonide; Child; Drug Delivery Systems; Fluocinolone Acetonide; Fluticasone; Humans; Mometasone Furoate; Pregnadienediols; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Structure-Activity Relationship; Tissue Distribution; Triamcinolone Acetonide

To determine whether inhaled steroid therapy causes delayed linear growth in children with asthma.. Medline (1966-1998), Embase (1980-1998), and Cinahl (1982-1998) databases and bibliographies of included studies were searched for randomized, controlled trials of inhaled steroid therapy in children with asthma that evaluated linear growth.. Studies were included if they met the following criteria: subjects 0 to 18 years of age with the clinical diagnosis of asthma; subjects randomized to inhaled beclomethasone, budesonide, flunisolide, fluticasone, or triamcinolone versus a nonsteroidal inhaled control for a minimum of 3 months; single- or double-blind; and outcome convertible to linear growth velocity. English- and non-English-language trials were included.. Data were extracted using a priori guidelines. Methodologic quality was assessed independently by both authors. Outcome was extracted as linear growth velocity.. Included trials were subgrouped by inhaled steroid. The beclomethasone subgroup, with 4 studies and 450 subjects, showed a decrease in linear growth velocity of 1.51 cm/year (95% confidence interval: 1.15,1.87). The fluticasone subgroup, with 1 study and 183 subjects, showed a decrease in linear growth velocity of.43 cm/year (95% confidence interval:.01,.85). Sensitivity analysis in the beclomethasone subgroup, which evaluated study quality, mode of medication delivery, control medication, and statistical model, showed similar results.. This meta-analysis suggests that moderate doses of beclomethasone and fluticasone in children with mild to moderate asthma cause a decrease in linear growth velocity of 1.51 cm/year and.43 cm/year, respectively. The effects of inhaled steroids when given for >54 weeks, or on final adult height, remain unknown.

Topics: Administration, Inhalation; Adolescent; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Body Height; Budesonide; Child; Child, Preschool; Fluocinolone Acetonide; Fluticasone; Growth; Humans; Infant; Infant, Newborn; Steroids; Triamcinolone

Intranasal steroids (INSs) are established as first-line treatment for allergic rhinitis. Extensive use of INSs with few reported adverse events supports the safety of these medications. Nevertheless, the prescription of more potent INSs for consistent and more prolonged use to younger and older patients, often in combination with inhaled corticosteroids, justifies the careful examination of their potential adverse systemic effects. Systemic bioavailability of INSs, by way of nasal and intestinal absorption, can be substantial; but current INSs vary significantly in their degree of first-pass hepatic inactivation and clearance from the body of the swallowed drug. For safety studies of INSs, distinguishing detectable physiologic perturbations from important adverse events is aided by an understanding of normal endocrine physiology and the methods used to test these systems. A review of available information indicates that (1) sensitive tests can measure the effects of INSs on biologic feedback systems, but they do not accurately predict clinically relevant adverse effects; (2) the primary factors that influence the relationship between therapeutic and adverse systemic effects of INSs are dosing frequency and efficiency of hepatic inactivation of swallowed drug; (3) INS treatment in recommended doses does not cause clinically significant hypothalamic-pituitary-adrenal axis suppression; (4) growth suppression can occur with twice-daily administration of certain INSs but does not appear to occur with once-daily dosing or with agents with more complete first-pass hepatic inactivation; (5) harmful effects of INSs on bone metabolism have not yet been adequately studied but would not be expected with the use of an INS dose and dosing frequency that do not suppress basal hypothalamic-pituitary-adrenal axis function or growth; and (6) these conclusions apply to INS treatment alone and in recommended doses-the risk of adverse effects in individual patients who are treated with INSs is increased by excessive dosing or concomitant inhaled corticosteroid or other topical corticosteroid therapy.

Topics: Administration, Intranasal; Androstadienes; Beclomethasone; Budesonide; Endocrinology; Fluocinolone Acetonide; Fluticasone; Humans; Mometasone Furoate; Pregnadienediols; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Steroids; Triamcinolone Acetonide

Inhaled corticosteroids are the treatment of choice for asthma. However, poor compliance by patients is one of the principal difficulties forced by clinicians. Thus, it seems important to propose the minimal daily number of doses. This study has compared the various modes of administration of inhaler corticosteroids and was carried out in patients with mild to moderate persistent asthma. Thus, comparing two to four doses per day shows an identical efficacy if the dose is less than 800 micrograms per day. At higher doses only two studies have been carried out and there are discordant results. The studies compare two doses versus one single dose per day and equally disagree with numerous works in favor of a single daily dose. In the single study carried out for at least twelve months the twice daily dose was the most effective. Thus it seems reasonable to suggest a single dose for mild persistent asthmatics. For moderate persistent asthmatics the choice between a single or twice daily dose would depend on the therapeutic compliance of the patient.

Topics: Administration, Inhalation; Administration, Topical; Adrenal Cortex Hormones; Adult; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Clinical Trials as Topic; Double-Blind Method; Drug Administration Schedule; Fluocinolone Acetonide; Humans; Placebos; Randomized Controlled Trials as Topic; Time Factors; Triamcinolone Acetonide

Topics: Administration, Inhalation; Administration, Topical; Adrenal Glands; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Dose-Response Relationship, Drug; Fluocinolone Acetonide; Fluticasone; Glucocorticoids; Growth; Humans; Osteoporosis; Pregnenediones; Triamcinolone Acetonide

Inhalation corticosteroids (beclometasone dipropionate, budesonide, flunisolide) proved effective against bronchial asthma (BA) and safe as they induce no severe systemic side effects. Of these three drugs side effects arise most frequently in administration of beclometasone dipropionate, least frequently of flunisolide. These inhalation corticosteroids are indicated both in non-steroid-dependent and steroid-dependent BA to reduce the dose of oral steroids or, if possible, for their complete discontinuation. Flunisolide is the most potent and effective of all inhalation corticosteroids used in current practice.

Topics: Administration, Inhalation; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Dose-Response Relationship, Drug; Drug Evaluation; Fluocinolone Acetonide; Humans; Pregnenediones; Prodrugs

The present review summarized the state of our knowledge on glucocorticosteroids, their mechanisms of action, pharmacological effects, pharmacokinetics and adverse effects. Oral steroids are very effective in treatment of asthma, however, when given in more than low doses and for a prolonged time, they may have quite serious side effects. The pharmacology of inhaled steroids is described. New inhaled glucocorticosteroids like budesonide and flunisolide are readily absorbed from the airway mucosa into the blood but are rapidly biotransformed in the liver into au inactive metabolite. Obviously the greatly reduces the risk of systemic side effects that exist with older glucocorticosteroids, e.g. dexamethasone.

Topics: Asthma; Budesonide; Dexamethasone; Dose-Response Relationship, Drug; Fluocinolone Acetonide; Glucocorticoids; Gonadal Steroid Hormones; Humans; Hydrocortisone; Liver; Pregnenediones

Owing to improvements made during the last 15 years in the pathophysiological and pharmacological research, many new corticosteroids have been successfully experimented. They have high activity on the target organ and they are suitable for long term therapies since they have not any systemic and/or local side effects. Nowadays the topical intranasal corticosteroid therapy is indispensable for allergic rhinitis treatment and it is very useful for many nasal and bronchopulmonary diseases (some chronic rhinitis, nasal polyposis, bronchial asthma, chronic obstructive bronchopulmonary diseases). The authors use their personal experience and carefully review the literature to describe the general aspects (pharmacology, pharmacokinetics, toxicology, side effects and contraindications) and to analyze the single drugs currently used in Italy and abroad. Finally, they compare the efficacy of each topical intranasal glucocorticoid among themselves and with other drugs.

Topics: Administration, Intranasal; Adrenal Cortex Hormones; Adult; Asthma; Beclomethasone; Budesonide; Child; Fluocinolone Acetonide; Humans; Hydrocortisone; Lung Diseases, Obstructive; Pregnenediones; Rhinitis

Topics: Administration, Intranasal; Adrenal Cortex Hormones; Asthma; Beclomethasone; Betamethasone; Budesonide; Drug Administration Schedule; Fluocinolone Acetonide; Humans; Pregnenediones; Triamcinolone Acetonide

The goal of this study was to establish a reliable method to evaluate systemic bioavailability and to determine equisystemic effects (microgram dose producing equal systemic cortisol suppression) of inhaled corticosteroids (ICS). Steroid naive asthma subjects (n = 156) were enrolled at six centers. A 1-week doubling dose design was used for each of six ICS and matched placebos for a total of four doses. Systemic effect was evaluated by hourly plasma cortisol concentrations (8 P.M. to 8 A.M.), 12- and 24-hour urine cortisol concentrations, and a morning blood osteocalcin. The area under the concentration-time curve for hourly cortisol concentrations was the best outcome variable to assess systemic effect. For the six ICS and matching placebos (beclomethasone-chlorofluorocarbon [CFC], budesonide dry powder inhaler [DPI], fluticasone DPI, fluticasone-CFC metered dose inhaler [MDI], flunisolide-CFC, and triamcinolone-CFC), only the placebo group and fluticasone DPI did not demonstrate a significant dose-response effect. Thus microgram comparison of all ICS could only be performed at a 10% cortisol suppression: flunisolide-CFC - 936; triamcinolone-CFC - 787; beclomethasone-CFC - 548; fluticasone DPI - 445; budesonide DPI - 268; fluticasone-CFC MDI - 111. This study represents the first step in evaluation of ICS efficacy based on equisystemic (cortisol suppression) effects of a given ICS, rather than doses judged arbitrarily to be comparable on a microgram basis.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Aged; Androstadienes; Asthma; Beclomethasone; Budesonide; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fluocinolone Acetonide; Fluticasone; Follow-Up Studies; Humans; Hydrocortisone; Male; Middle Aged; Probability; Reference Values; Single-Blind Method; Treatment Outcome; Triamcinolone

There is a limited body of evidence comparing the clinical effects of different inhaled corticosteroids in the treatment of asthma. This study compared the safety and efficacy of inhaled flunisolide and budesonide, both with unique delivery systems that may affect clinical response.. This multicenter study was carried out to compare the efficacy and safety of flunisolide, administered via AeroChamber, with budesonide, administered via Turbuhaler, in the treatment of moderate asthma.. Patients with moderate asthma, defined as an FEV1 of 40% to 85% of predicted, underwent a 2-week run-in period during which beclomethasone, 750 microg twice daily by MDI, was administered, along with salbutamol prn. Patients (n = 176) were then randomized into two groups. One group received flunisolide administered via AeroChamber, 750 microg (3 puffs), twice daily. The second group received budesonide administered via Turbuhaler, 600 microg (3 puffs), twice daily. All patients took salbutamol prn.. At the end of the 6-week treatment period, there were no significant differences (P > .05 for all comparisons) in efficacy between the groups as evaluated by any efficacy parameter. The treatment groups also did not differ significantly in the number of adverse events or in the incidence of oropharyngeal Candida infection.. Flunisolide administered by AeroChamber and budesonide administered via Turbuhaler demonstrate similar efficacy and safety in the treatment of moderate asthma.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Asthma; Budesonide; Drug Tolerance; Female; Fluocinolone Acetonide; Humans; Hydrocortisone; Male; Middle Aged; Nebulizers and Vaporizers; Therapeutic Equivalency

Recent studies suggest that inhaled corticosteroids may differ significantly in their systemic effects.. To compare the systemic effects, as measured by plasma cortisol suppression, of inhaled beclomethasone dipropionate, budesonide, flunisolide, fluticasone propionate, and triamcinolone acetonide at doses of approximately 1000 microg twice daily.. Sixty healthy adult male volunteers participated in this randomized, open-label, parallel-design study. Twenty-four-hour plasma cortisol determinations (cortisol-AUC24) were measured after a single dose of placebo medication and after a single dose and 7 consecutive doses of active medication.. After a single dose, all inhaled corticosteroid preparations caused statistically significant mean reductions in cortisol-AUC24 compared with placebo as follows: flunisolide, 7% (P= .02); budesonide, 16% (P= .001); beclomethasone, 18% (P= .003); triamcinolone, 19% (P=.001); and fluticasone, 35% (P<.001). After multiple doses, flunisolide was not significantly different from placebo (5%; P = .24), while budesonide (18%; P = .002), triamcinolone (25%; P<.001), beclomethasone (28%; P<.001), and fluticasone (79%; P<.001) all resulted in statistically significant suppression of cortisol-AUC24. After both single and multiple doses, beclomethasone, budesonide, flunisolide, and triamcinolone were not statistically different from each other, while fluticasone was significantly (P<.001) more suppressive than the other 4 medications.. These results indicate that there are differences in the systemic effects of inhaled corticosteroids when used in high doses and emphasize the importance of using the minimum dose of inhaled corticosteroids required to maintain control of asthma symptoms.

Topics: Administration, Inhalation; Administration, Topical; Androstadienes; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Fluocinolone Acetonide; Fluticasone; Glucocorticoids; Humans; Hydrocortisone; Male; Reference Values; Triamcinolone Acetonide; Volunteers

Topics: Administration, Topical; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Beclomethasone; Budesonide; Child; Fluocinolone Acetonide; Fluticasone; Humans; Hydrocortisone; Male; Pregnenediones; Triamcinolone Acetonide

A group comparative study was carried out in 60 patients suffering from seasonal allergic rhinitis in order to evaluate the effects and side effects of the recently introduced glucocorticoids budesonide and flunisolide delivered as nasal sprays. Symptom scores for nasal and ocular symptoms as well as pollen counts were registered daily for one month. Both treatments provided excellent control of nasal symptoms. However, a significantly higher number of patients in the flunisolide group complained about nasal irritation.

Topics: Adolescent; Adult; Aerosols; Budesonide; Epistaxis; Female; Fluocinolone Acetonide; Humans; Male; Middle Aged; Pregnenediones; Random Allocation; Rhinitis, Allergic, Seasonal

Human immunodeficiency virus (HIV) continues to be a major contributor to morbidity and mortality worldwide, particularly in developing nations where high cost and logistical issues severely limit the use of current HIV therapeutics. This, combined HIV's high propensity to develop resistance, means that new antiviral agents against novel targets are still urgently required. We previously identified novel anti-HIV agents directed against the nuclear import of the HIV integrase (IN) protein, which plays critical roles in the HIV lifecycle inside the cell nucleus, as well as in transporting the HIV preintegration complex (PIC) into the nucleus. Here we investigate the structure activity relationship of a series of these compounds for the first time, including a newly identified anti-IN compound, budesonide, showing that the extent of binding to the IN core domain correlates directly with the ability of the compound to inhibit IN nuclear transport in a permeabilised cell system. Importantly, compounds that inhibited the nuclear transport of IN were found to significantly decrease HIV viral replication, even in a dividing cell system. Significantly, budesonide or its analogue flunisolide, were able to effect a significant reduction in the presence of specific nuclear forms of the HIV DNA (2-LTR circles), suggesting that the inhibitors work though blocking IN, and potentially PIC, nuclear import. The work presented here represents a platform for further development of these specific inhibitors of HIV replication with therapeutic and prophylactic potential.

Topics: Active Transport, Cell Nucleus; Animals; Budesonide; Cell Line; Fluocinolone Acetonide; HIV; HIV Integrase; HIV Integrase Inhibitors; Humans; Protein Binding; Rats; Structure-Activity Relationship; Virus Integration; Virus Replication

This study investigated the effect of different active pharmaceutical ingredients (API) on aerosol electrostatic charges and aerosol performances for pressurized metered dose inhalers (pMDIs), using both insulating and conducting actuators.. Five solution-based pMDIs containing different API ingredients including: beclomethasone dipropionate (BDP), budesonide (BUD), flunisolide (FS), salbutamol base (SB) and ipratropium bromide (IPBr) were prepared using pressure filling technique. Actuator blocks made from nylon, polytetrafluoroethylene (PTFE) and aluminium were manufactured with 0.3 mm nominal orifice diameter and cone nozzle shape. Aerosol electrostatics for each pMDI formulation and actuator were evaluated using the electrical low-pressure impactor (ELPI) and drug depositions were analysed using high performance liquid chromatography (HPLC).. All three actuator materials showed the same net charge trend across the five active drug ingredients, with BDP, BUD and FS showing positive net charges for both nylon and PTFE actuators, respectively. While SB and IPBr had significantly negative net charges across the three different actuators, which correlates to the ionic functional groups present on the drug molecule structures.. The API present in a pMDI has a dominant effect on the electrostatic properties of the formulation, overcoming the charge effect arising from the actuator materials. Results have shown that the electrostatic charges for a solution-based pMDI could be related to the interactions of the chemical ingredients and change in the work function for the overall formulation.

Topics: Aerosols; Albuterol; Beclomethasone; Budesonide; Chemistry, Pharmaceutical; Fluocinolone Acetonide; Ipratropium; Metered Dose Inhalers; Particle Size; Pharmaceutical Preparations; Pressure; Solutions; Static Electricity

Asthma is one of the most prevalent diseases in the world, for which the mainstay treatment has been inhaled glucocorticoids (GCs). Despite the widespread use of these drugs, approximately 30% of asthma sufferers exhibit some degree of steroid insensitivity or are refractory to inhaled GCs. One hypothesis to explain this phenomenon is interpatient variability in the clearance of these compounds. The objective of this research is to determine how metabolism of GCs by the CYP3A family of enzymes could affect their effectiveness in asthmatic patients. In this work, the metabolism of four frequently prescribed inhaled GCs, triamcinolone acetonide, flunisolide, budesonide, and fluticasone propionate, by the CYP3A family of enzymes was studied to identify differences in their rates of clearance and to identify their metabolites. Both interenzyme and interdrug variability in rates of metabolism and metabolic fate were observed. CYP3A4 was the most efficient metabolic catalyst for all the compounds, and CYP3A7 had the slowest rates. CYP3A5, which is particularly relevant to GC metabolism in the lungs, was also shown to efficiently metabolize triamcinolone acetonide, budesonide, and fluticasone propionate. In contrast, flunisolide was only metabolized via CYP3A4, with no significant turnover by CYP3A5 or CYP3A7. Common metabolites included 6β-hydroxylation and Δ(6)-dehydrogenation for triamcinolone acetonide, budesonide, and flunisolide. The structure of Δ(6)-flunisolide was unambiguously established by NMR analysis. Metabolism also occurred on the D-ring substituents, including the 21-carboxy metabolites for triamcinolone acetonide and flunisolide. The novel metabolite 21-nortriamcinolone acetonide was also identified by liquid chromatography-mass spectrometry and NMR analysis.

Topics: Administration, Inhalation; Androstadienes; Anti-Asthmatic Agents; Aryl Hydrocarbon Hydroxylases; Biotransformation; Budesonide; Catalysis; Chromatography, High Pressure Liquid; Cytochrome P-450 CYP3A; Fluocinolone Acetonide; Fluticasone; Glucocorticoids; Humans; Hydroxylation; Isoenzymes; Kinetics; Lung; Magnetic Resonance Spectroscopy; Mass Spectrometry; Molecular Structure; Recombinant Proteins; Triamcinolone Acetonide

Inhaled corticosteroids (ICS) are a mainstay anti-inflammatory therapy for the management of asthma. ICS are synthetic glucocorticoids that are structurally similar to the natural active human glucocorticoid cortisol. Steroid transforming enzymes of the aldo-keto reductase (AKR) family, namely AKR1D1 (5β-steroid reductase) and AKR1C1-4 (ketosteroid reductases) are implicated in the systemic metabolism of cortisol in liver. In this study, the activities of these AKR1 enzymes on cortisol and two ICS compounds budesonide (BUD) and flunisolide (FLU) were investigated. It was found that the catalytic efficiency of AKR1D1 for the reduction of the double bond in cortisol was 4- and 10-fold higher than the catalytic efficiencies of AKR1D1 with FLU and BUD, respectively. This suggests that compared to cortisol, for which the 5β-reduction is a major metabolic pathway, a lower degree of systemic (hepatic) metabolism of BUD and FLU via AKR1D1 takes place. In addition, BUD potently inhibited AKR1D1 and AKR1C4, the key steroid metabolizing enzymes in liver, which may disrupt endogenous steroid hormone metabolism and thus contribute to BUD-induced systemic effects. Activities of AKR1C1-3 on cortisol and the two ICS compounds (targeting the 20-keto group) suggest these enzymes may be involved in the local (lung) metabolism of these glucocorticoids.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Budesonide; Drug Resistance; Fluocinolone Acetonide; Humans; Hydrocortisone; Oxidation-Reduction; Oxidoreductases

Intranasal corticosteroids (INS) are the first line treatment for allergic rhinitis (AR). To guide clinical decision-making, we created a therapeutic index (TIX) for INS reflecting efficacy and safety.. A Medline search (1966 to June 2009) was carried out to identify all placebo-controlled randomized trials, and observational reports for safety issues, with Dexamethasone, Budesonide (BUD), Fluticasone propionate (FP), Fluticasone furoate (FF), Flunisolide, Mometasone furoate (MF), Triamcinolone (TRIAM), and Beclomethasone dipropionate (BDP) as treatment for AR. Data on three efficacy (nasal symptoms, ocular symptoms, global assessment) and three safety outcomes (epistaxis, growth, systemic ocular effects) were extracted. Meta analyses were performed for each INS and outcome and results were categorised into scores by quartiles. Scores of the three efficacy and safety outcomes were summed up to create summation scores for efficacy (ES) and side effects (AES), respectively with a maximum of 9 points. The TIX was then defined as the ratio of ES and AES.. Data of 84 studies were extracted. Based on availability of data, a TIX was calculated for 6 substances. BUD showed the highest efficacy score followed by MF and TRIAM. The lowest scores for side effects were achieved by MF and TRIAM followed by FP. These findings resulted in TIX scores of 7 and 5 for MF and TRIAM, respectively, indicating a high efficacy and low potential of adverse events. Medium scores were reached by BUD and FP and lower scores by BDP and FF.. Although safety and efficacy is proven for all available INS by multiple studies, the systematic aggregation and analysis of data allows for a differentiated summary on clinically important features.

Topics: Administration, Intranasal; Androstadienes; Anti-Inflammatory Agents; Beclomethasone; Budesonide; Fluocinolone Acetonide; Fluticasone; Glucocorticoids; Humans; Mometasone Furoate; Pregnadienediols; Rhinitis, Allergic, Perennial; Treatment Outcome; Triamcinolone

The purpose of this study was to compare the toxicity of three marketed corticosteroid receptor agonists (mometasone furoate, budesonide, or flunisolide) to the stomach of female CD-1 mice following oral administration via the diet for up to 52 weeks, with a 16-week recovery period (budesonide and flunisolide). A range of tissues was examined by light microscopy, accompanied by clinical pathology measurements to assess anticipated corticosteroid effects as a surrogate marker of systemic drug exposure. Microscopic changes seen in the stomach with each corticosteroid included pyloric hyalinization. This previously unreported finding was investigated using histochemical and immunohistochemical techniques and was found to consist of hyalinized collagen, in association with increased immunohistochemical signal for transglutaminase-2 and osteopontin. The significance of the osteopontin finding is unclear; however, the ability of transglutaminase-2 to facilitate the formation of degradation resistant protein bonds implies this protein may be involved in the pathogenesis of this change. Furthermore, published evidence that transglutaminase-2 may be induced by a corticosteroid agonist raises the possibility that pyloric stomach hyalinization may be a class effect of corticosteroids via the action of this enzyme.

Topics: Administration, Oral; Adrenal Cortex Hormones; Animals; Anti-Inflammatory Agents; Budesonide; Female; Fluocinolone Acetonide; GTP-Binding Proteins; Hyalin; Mice; Mice, Inbred Strains; Microscopy, Electron; Mometasone Furoate; Osteopontin; Pregnadienediols; Protein Glutamine gamma Glutamyltransferase 2; Pylorus; Transglutaminases

Three spontaneous reports of patients in whom a relationship between hypertrichosis and inhaled corticosteroids (ICS) was suspected, were reported to Lareb, The Netherlands Pharmacovigilance Center. We sought evidence for and against a causal relationship between hypertrichosis and ICS in children. The relationship between hypertrichosis and ICS was studied mathematically by assessing the Reporting Odds Ratio (ROR) and by determining the Naranjo Score (NS). We also studied the reports sent to the Pharmacovigilance Database of the Uppsala Monitoring Centre (UMC) of the WHO and reviewed the literature. In the Dutch children, the ROR between hypertrichosis and ICS was 14.6 (95%CI 3.6-59.5), the NS was 4. In the database of the UMC 20 more reports on hypertrichosis and ICS were found, contributing to the results of the Dutch database. Taken together, 11 boys and 12 girls were involved with a mean age of 7 years (range 1-17). The time between the start of ICS and the occurrence of hypertrichosis varied between 1 month and 3 years. Besides the hypertrichosis, growth retardation was found in 5 children and adrenal suppression in 12. In 12 children the outcome after cessation was reported: in 6 children the hypertrichosis improved, whilst in 6 it did not. We found sufficient evidence to support the suspicion that hypertrichosis might be a true adverse effect of ICS. We found no simple dose-effect relationship but obviously there is an individual susceptibility. After cessation of ICS the exaggerated hair growth will not disappear in all children. Hypertrichosis may be a useful clinical pointer to exogenous steroid excess.

Topics: Adolescent; Androstadienes; Asthma; Beclomethasone; Budesonide; Child; Child, Preschool; Databases as Topic; Female; Fluocinolone Acetonide; Fluticasone; Glucocorticoids; Humans; Hypertrichosis; Infant; Male; Nebulizers and Vaporizers

Budesonide and flunisolide anhydrate were crystallized using the solution enhanced dispersion by supercritical fluids (SEDS) technique. The aim was to investigate the possibility of preparing different pure polymorphs.. 0.25% w/v solutions of each drug were prepared from acetone and methanol. Operating conditions were 40-80 degrees C and 80-200 bars. The flow rate of drug solution was 0.3 mL/min and that of CO2 was 9-25 mL/min. Sample characterizations included differential scanning calorimetry, X-ray powder diffraction, variable temperature X-ray diffraction, scanning electron microscopy, and solubility studies.. The particle morphology of budesonide was dependent on the nature of the solvent. SEDS processing of flunisolide with acetone at 100 bars resulted in the formation of polymorphic mixtures at 80 degrees C and a new polymorph III at 60 C and 40 degrees C. With methanol at 100 bars another new polymorph IV was formed with different particle morphology at 80 degrees C and a polymorphic mixture at 60 degrees C.. Using the SEDS, microparticles of crystalline budesonide were prepared and new polymorphs of flunisolide were produced. Particle characteristics were controlled by the temperature, pressure and relative flow rates of drug solution and CO2.

Topics: Budesonide; Crystallization; Fluocinolone Acetonide; Solvents

A retrospective cohort using pharmacy and medical claims was analysed to determine whether the differences in efficacy of various inhaled corticosteroids demonstrated in clinical trials lead to differences in costs of care observed in clinical practice. Subjects that had an ICD-9 (493.XX) code for asthma and a new pharmacy claim for inhaled fluticasone propionate 44 mcg (FP), beclomethasone dipropionate (BDP), triamcinolone acetonide (TAA), budesonide (BUD) or flunisolide (FLU) were identified and followed for 12 months. Annual asthma care charges (pharmacy and medical) over the 12-month observation period were significantly (P < 0.03) higher in patients treated with BDPTAA, BUD and FLU compared to FP, 24%, 27%, 34% and 45% respectively In addition, patients treated with BDPTAA, and FLU were associated with significantly (P < 0.005) higher total healthcare (asthma + non-asthma) charges compared to patients on FP, 53%, 46% and 39% respectively Asthma care and total healthcare charges remained lower for FP after including FP110 mcg and excluding patients who were extreme cost outliers (+/- 2 SD from the mean) in a univariate sensitivity analysis. This analysis supports recent randomized control trials that FP offers a superior efficacy profile at lower asthma care as well as total healthcare charges compared to other inhaled corticosteroids.

Topics: Administration, Inhalation; Adolescent; Adult; Androstadienes; Asthma; Beclomethasone; Budesonide; Child; Child, Preschool; Cost-Benefit Analysis; Databases, Factual; Drug Costs; Fluocinolone Acetonide; Fluticasone; Follow-Up Studies; Glucocorticoids; Humans; Middle Aged; Retrospective Studies; Triamcinolone

Different glucocorticoids have been compared with respect to the inhibition of corticotropin-releasing factor (CRF)-mediated adrenocorticotropin (ACTH) secretion from pituitary fragments of the rat. The influence of time of exposure to glucocorticoids and glucocorticoid concentration has been investigated. CRF-stimulated ACTH secretion of perifused rat pituitary fragments was measured by a chemiluminescence immunoassay. ACTH secretion was monitored over three days. Inhibition of CRF-stimulated ACTH secretion by glucocorticoids was quantified by the area under the curve of CRF-stimulated ACTH secretion over baseline. Concentrations needed to inhibit ACTH secretion decreased with the receptor affinities of the glucocorticoids as follows: fluticasone propionate; receptor affinity 1800, concentration 10(-8) M; budesonide, 935 and 3-2.5 x 10(-8) M; flunisolide, 478 and 5 x 10(-7) M; prednisolone, 10 and 10(-6) M. CRF-stimulated secretion was inhibited by glucocorticoids after incubation for 1 min at concentrations between 10(-8) and 10(-6) M. The same absolute quantity of the glucocorticoids produced no inhibition when incubation was prolonged to 50 min or when a lower concentration was used. Immediately after the perifusion stimulation of ACTH secretion was observed. The results suggest the possibility of minimizing the side effects of glucocorticoids by prolonging drug release.

Topics: Administration, Topical; Adrenocorticotropic Hormone; Androstadienes; Animals; Anti-Inflammatory Agents; Area Under Curve; Budesonide; Corticotropin-Releasing Hormone; Fluocinolone Acetonide; Fluticasone; Glucocorticoids; Male; Pituitary Gland; Prednisolone; Rats; Rats, Wistar; Time Factors

Intranasal application of glucocorticoids is an efficacious treatment of allergic rhinitis and some cases of nonallergic rhinitis. However, no data on binding of glucocorticoids to nasal tissue are available. Pronounced binding of the compound to the target tissue is favorable as it might serve as a local deposit delivering the glucocorticoid to specific receptors and it slows down the efflux of the compound into systemic circulation.. Human nasal tissue was incubated with fluticasone propionate, budesonide, flunisolide and beclomethasone-17-monopropionate. Kinetics of binding and redistribution of the tissue-bound fraction into human plasma was monitored.. Binding of glucocorticoids to human nasal tissue was fast and highest for the lipophilic fluticasone propionate, followed by beclomethasone-17-monopropionate. Also, highest concentrations of these lipophilic glucocorticoids remained in nasal tissue after equilibration of drug-saturated tissue with plasma.. Lipophilic compounds exhibit a high tissue binding and retention which is an important property of topically applied glucocorticoids. It is the basis for prolonged action and low concentration of the compound in systemic circulation.

Topics: Administration, Topical; Androstadienes; Anti-Allergic Agents; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Beclomethasone; Budesonide; Fluocinolone Acetonide; Fluticasone; Glucocorticoids; Humans; In Vitro Techniques; Kinetics; Nasal Mucosa; Receptors, Glucocorticoid

Topics: Administration, Inhalation; Androstadienes; Anti-Inflammatory Agents; Area Under Curve; Budesonide; Fluocinolone Acetonide; Fluticasone; Glucocorticoids; Humans; Hydrocortisone

The objective of the study was to develop an algorithm based on a pharmacokinetic-pharmacodynamic (PK/PD) modeling approach to quantify and predict cumulative cortisol suppression (CCS) as a surrogate marker for the systemic activity of inhaled corticosteroid therapy. Two Excel spreadsheets, one for single dose and another for steady-state multiple doses of inhaled steroids, were developed for predicting CCS. Four of the commonly used inhaled steroids were chosen for the purposes of simulation: fluticasone propionate (FP), budesonide (BUD), flunisolide (FLU), and triamcinolone acetonide (TAA). Drug-specific PK and PD parameters were obtained from previous single- and multiple-dose studies. In cases in which multiple-dose data were not available, the single-dose data were extrapolated. The algorithm was designed to calculate CCS based on 5 input parameters: name of drug, dose, dosing interval, time(s) of dosing, and type of inhaler device. In addition, a generalized algorithm was set up to calculate CCS based on clearance, volume of distribution, absorption rate, protein binding, pulmonary deposition, oral bioavailability, and unbound EC50 of the corticosteroid of interest. The spreadsheet allowed predictions of CCS for single doses as well as steady-state conditions. A simple method has been developed that facilitates comparisons between various drugs and dosing regimens and has the potential to significantly reduce the number of comparative clinical trials to be performed for evaluating the short-term systemic activity of inhaled corticosteroids.

Topics: Administration, Inhalation; Administration, Topical; Algorithms; Androstadienes; Anti-Inflammatory Agents; Budesonide; Depression, Chemical; Fluocinolone Acetonide; Fluticasone; Humans; Hydrocortisone; Models, Biological; Nebulizers and Vaporizers; Triamcinolone Acetonide

Fifty rats were treated with topical nasal steroids with and without the preservative benzalkonium chloride in their right nostril twice daily for 21 days, while the left nostrils were exposed to 0.9% NaCl. By cutting the noses serially in frontal sections, the structure of the mucosal lining of all parts of the nose could be investigated. Areas with squamous cell metaplasia were observed in all nostrils exposed to topical steroids containing benzalkonium chloride. Such alterations were not observed in any nasal cavities exposed to the topical nasal steroid without the preservative or to 0.9% NaCl. In conclusion, benzalkonium chloride appears to be potentially toxic to the mucosa in vivo.

Topics: Administration, Topical; Aerosols; Animals; Anti-Inflammatory Agents; Beclomethasone; Benzalkonium Compounds; Bronchodilator Agents; Budesonide; Fluocinolone Acetonide; Glucocorticoids; Male; Nasal Mucosa; Nasal Septum; Pregnenediones; Preservatives, Pharmaceutical; Rats; Rats, Inbred Strains

In inhalation therapy preservation of the stability of an aerosolized drug molecule while nebulisation is an important factor determining its clinical efficacy and safety. The influence of nebulisation with employment of ultrasonic and jet methods using compressed air and oxygen as aerosol carriers on the stability of inhaled hydrocortisone hemisuccinate, budesonide and flunisolide was investigated. Collected aerosol samples were analyzed using thin layer chromatography and compared with standard solution samples in UV-wavelength chi = 254 nm. The appearance of additional fluorescence exctinction points by ultrasonic and air jet methods produced hydrocortisone hemisuccinate aerosol samples and by an ultrasonic method produced budesonide aerosol sample were observed. This could provide evidence for affecting stability and appearance of desintegration products of hydrocortisone hemisuccinate and budesonide while nebulisation using aforementioned methods. In the context of the obtained results the stability of a flunisolide molecule remains unaffected. Furthermore, the process of steroids solution condensation on the membrane of the nebuliser and in inhalation vessel were seen. The phenomena of molecule desintegration and solution condensation as well stated while nebulisation lead to reduction of the inhaled steroid dose accessible for a patient.

Topics: Administration, Inhalation; Aerosols; Air; Anti-Inflammatory Agents; Budesonide; Chemistry, Pharmaceutical; Chromatography, Thin Layer; Drug Stability; Fluocinolone Acetonide; Glucocorticoids; Hydrocortisone; Nebulizers and Vaporizers; Oxygen

To examine recent trends in the use of inhaled beta 2-adrenergic agonists and inhaled corticosteroids for the treatment of asthma among Saskatchewan residents and to determine whether these trends are in keeping with widely publicized guidelines recommending a reduction in the use of agents to treat symptoms (i.e., inhaled beta 2-adrenergic agonists) and increased use of prophylactic agents (i.e., inhaled corticosteroids).. Descriptive pharmacoepidemiologic study conducted with the use of data from the computerized database of the Saskatchewan Prescription Drug Plan.. Saskatchewan.. Saskatchewan residents 5 to 54 years of age who received one or more outpatient prescriptions for drugs to treat asthma (inhaled drugs, ingested beta 2-adrenergic agonists and ingested methylxanthines) from 1989 to 1993.. Epidemiologic trends, calculated for each year: number of prescriptions per 1,000 persons; number of patients who received prescriptions for inhaled corticosteroids, inhaled beta 2-adrenergic agonists and any type of drug to treat asthma; mean number of such prescriptions per patient; and weighted mean amount of salbutamol, fenoterol and beclomethasone dispensed per patient.. There has been an increase in the proportion of the population receiving prescriptions for drugs to treat asthma. The number of patients receiving these drugs per 1,000 people rose during the study period from 33.38 to 46.59 for any drug to treat asthma, from 24.70 to 33.77 for inhaled beta 2-adrenergic agonists and from 6.1 to 19.9 for inhaled corticosteroids. The mean number of prescriptions per patient decreased steadily for all drugs to treat asthma (from 5.34 in 1989 to 3.88 in 1993), for inhaled beta 2-adrenergic agonists (from 4.35 to 3.09) and for inhaled corticosteroids (from 2.98 to 2.25). The weighted mean amount of inhaled salbutamol dispensed per patient per year decreased by 40%, from 178.08 mg in 1989 to 109.14 mg in 1993. The weighted amount of fenoterol dispensed per patient per year declined even more, by 58%, from 387.91 mg in 1989 to 164.00 mg in 1993. Conversely, the weighted amount of inhaled beclomethasone dispensed per patient per year increased by 35% from 46.95 mg in 1989 to 63.50 mg in 1992, then dropped to 56.17 mg per year in 1993.. These data demonstrate a substantial change in Saskatchewan in the prescribing of drugs to treat asthma; they suggest that many physicians responded to current guidelines advocating increased attention to prevention of airway inflammation in the treatment of asthma.

Topics: Administration, Inhalation; Administration, Topical; Adolescent; Adrenergic beta-Agonists; Adult; Aerosols; Albuterol; Anti-Inflammatory Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Child; Child, Preschool; Drug Prescriptions; Drug Utilization Review; Fenoterol; Fluocinolone Acetonide; Glucocorticoids; Humans; Isoproterenol; Metaproterenol; Middle Aged; Pregnenediones; Procaterol; Saskatchewan; Triamcinolone

A follow-up study on 180 patients treated for the first time for nasal polyps was performed. The follow-up period was from 1 to 8 years with a median of 57 months. The majority of patients had postoperative topical steroid treatment. 65.6% of patients had one polypectomy, 17.8% had two polypectomies, 10% had 3, 2.8% had 4, and 3.9% of patients had 5-10 polypectomies performed during the follow-up period. Patients without asthma, acute recurrent or chronic sinusitis, acetylsalicylic acid intolerance, or allergy had fewer polypectomies and less topical steroid treatment than patients with these characteristics. The recurrence profile between the first and second polypectomy described with the life-table method showed a slow decline in the number of patients with only one polypectomy. The time span needed before significant clinical symptoms occurred after the first polypectomy indicates that not all primary polyp patients are prone to recurrence. Nasal polyps is probably a manifestation of different clinical and aetio-pathogenetic entities. Further identification of such entities is needed to improve treatment strategy.

Topics: Adolescent; Adult; Aerosols; Aged; Aged, 80 and over; Beclomethasone; Budesonide; Child; Combined Modality Therapy; Denmark; Female; Fluocinolone Acetonide; Follow-Up Studies; Humans; Male; Middle Aged; Nasal Polyps; Pregnenediones; Recurrence

Topics: Administration, Inhalation; Administration, Topical; Adult; Anti-Inflammatory Agents; Bronchodilator Agents; Budesonide; Child; Dose-Response Relationship, Drug; Fluocinolone Acetonide; Humans; Lung Diseases, Obstructive; Pregnenediones

Failure to get relief from topical steroid nasal spray is often blamed on poor administration knowledge. In a population of patients referred to the rhinitis clinic who have failed to get relief from topical steroid nasal spray when prescribed by the general practitioner, lack of patient education only accounts for 28 per cent of patient treatment failures and other factors e.g. poor compliance, erroneous diagnosis or severity of rhinitis will be responsible for the rest. Information leaflets are considered to be a good idea by nearly all patients but this study demonstrates that they would only be of therapeutic benefit to a minority of patients.

Topics: Administration, Intranasal; Adolescent; Adult; Aged; Anti-Inflammatory Agents; Beclomethasone; Budesonide; Female; Fluocinolone Acetonide; Glucocorticoids; Humans; Male; Middle Aged; Patient Education as Topic; Pregnenediones; Rhinitis; Self Administration