Fluticasone

Fig. 29. Examples of topical antiasthma corticosteroids that are rapidly broken down in the circulation fluticasone [90566-53-3] (288), monetasone...

Reaction of etio acid 67 with N,N-dimethylthioformamidoyl chloride probably gives initially the mixed anhydride 71 this is not isolated but undergoes O to S carbonyl migration to the anhydride 72. Saponification then leads to the thioacid 73. Reaction of the sodium salt of the acid witli bromochloromethane affords cloticasone propionate (74). The corresponding reaction with hioniofluoromethane leads to fluticasone propionate (75) [16]. 

Clobetasol Propionate Qobetasone Butyrate Desoximetasone Fluticasone Propionate Halcinonide Mometasone... 

Asthma is a chronic inflammatory disease. Therefore steroids represent the most important and most frequently used medication. Already after the fust treatment, steroids reduce cellular infiltration, inflammation, and the LAR, whereas changes in the EAR require prolonged treatment to lower the existent IgE levels. The mechanisms of steroid actions are complex and only incompletely understood. Besides their general antiinflammatory properties (see chapter glucocorticoids), the reduction of IL-4 and IL-5 production from T-lymphocytes is particularly important for asthma therapy. The introduction of inhaled steroids, which have dramatically limited side effects of steroids, is considered one of the most important advancements in asthma therapy. Inhaled steroids (beclomethasone, budesonide, fluticasone, triamcinolone, momethasone) are used in mild, moderate, and partially also in severe asthma oral steroids are used only in severe asthma and the treatment of status asthmaticus. Minor side effects of most inhaled steroids are hoarseness and candidasis, which are avoided by the prodrug steroid ciclesonide. 

Inhaled steroids (commonly used are beclomethasone, budesonide, triamcinolone, fluticasone, flunisolide) appear to attenuate the inflammatory response, to reduce bronchial hyperreactivity, to decrease exacerbations and to improve health status they may also reduce the risk of myocar dial infar ction, but they do not modify the longterm decline in lung function. Whether- steroids affect mortality remains unclear. Many patients appear to be resistant to steroids and large, long-term trials have shown only limited effectiveness of inhaled corticosteroid ther apy. Certainly, the benefit from steroids is smaller in COPD than in asthma. Topical side-effects of inhaled steroids are oropharyngeal candidiasis and hoarse voice. At the normal doses systemic side-effects of inhaled steroids have not been firmly established. The current recommendation is that the addition of inhaled gluco-coiticosteroids to bronchodilator treatment is appropriate for patients with severe to veiy sever e COPD. 

Antihistamines are drags used to counteract the effects of histamine on body organs and structures. Examples of antihistamines include diphenhydramine (Benadryl), loratadine (Claritin), fexofenadine (Allegra), and cetirizine (Zyrtec). A new antihistamine, deslorata-dine (Clarinex), is die active metabolite of loratadine and is intended to eventually replace loratadine (Claritin). Topical corticosteroid nasal sprays such as fluticasone propionate (Flonase) or triamcinolone ace-tonide (Nasacort AQ) are also used for nasal allergy symptoms. See Chapter 56 for more information on die topical corticosteroids. 

EP416950 (Glaxo appl. 7.9.1990 GB-prior, 8.9.1989 20.10,1989). combination with fluticasone ... 

C24H3,F20v5 80474-45-9) see Fluticasone propionate (6a, 11 p, 16ot, 17a)-6,9-difluoro-l 1-hydroxy- 16-methyl-3-oxo-17-(l-oxopropoxy)andro5ta-l 4-diene-17-carboxylic acid... 

C24H3()F20ft 65429-42-7) see Fluticasone propionate (A)-3,4-difluoro-2-(2-hydroxypropoxy)-l-nitrobenzene (C,HyF2N04 124409-94-5) see Levofloxacin... 

CH2FI 373-53-5) see Fluticasone propionate 5-fluoroisatoic anhydride (C8H4FNO3 321-69-7) see Flumazenil... 

C3H5CIO 79-03-8) see Betamethasone butyrate propionate Betamethasone dipropionate Docarpamine Erythromycin estolate Erythromycin monopropionate mercaptosuccinate Flavoxate Fluticasone propionate Naproxen Prednicarbate Quinethazone 2-propionyloxybenzoic acid (Ci H,o04 6328-44-5) see Flavoxate... 

Salmeterol is also available in a fixed ratio combination product containing fluticasone, and a new drug application has been filed for a fixed combination product containing budesonide and formoterol. Combination products have the potential advantage of increasing patient adherence due to the decreased number of inhalers and inhalations however, these products offer less flexibility with respect to dosage adjustments when necessary. 

Fluticasone nasal spray, one spray in each nostril daily during allergy season... 

Currently, six intranasal corticosteroids—beclomethasone, budesonide, flunisolide, fluticasone, mometasone, and triamcinolone—are available commercially. Although all... 

Intranasal corticosteroids are the most effective anti-inflammatory agents used in pediatric patients with allergic rhinitis. Although fewer studies have been conducted in children, results demonstrate that intranasal corticosteroids are effective and well tolerated, with an adverse-effect profile similar to placebo. Mometasone is indicated for children as young as 2 years of age, fluticasone is indicated for children 4 years of age and older, and beclomethasone, budesonide, flunisolide, and triamcinolone are indicated for children 6 years and older.15 Because concerns regarding effect of intranasal steroids on growth exist, the growth of pediatric patients prescribed intranasal steroids should be monitored routinely via stadiometry. 

Anderson W, Kalberg C, Edwards L et al. Effects of polymorphisms in the promoter region of 5-lipoxygenase and LTC4 synthase on the clinical response to Za-firlukast and Fluticasone. Eur Respir J 2000 16 183s. 

Several studies have shown an additive effect with the combination of inhaled corticosteroids and long-acting bronchodilators. Combination therapy with salmeterol plus fluticasone or formoterol plus budesonide is associated with greater improvements in FEVj, health status, and exacerbation frequency than either agent alone. The availability of combination inhalers makes administration of both drugs convenient and decreases the total number of inhalations needed daily. 

Flonase 50 meg per actuation (fluticasone propionate) 2 sprays in each nostril qd... 

Borchard G, Cassara ML, Roemele PE, Florea BI, Junginger HE (2002) Transport and local metabolism of budesonide and fluticasone propionate in a human bronchial epithelial cell line (Calu-3). J Pharm Sci 91(6) 1561—1567. 

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