Glucocorticoid budesonide

Ryrfeldt A, Persson G, Nilsson E (1989) Pulmonary disposition of the potent glucocorticoid budesonide, evaluated in an isolated and perfused rat lung model. Biochem Pharmacol 38 17-22. 

Dahl back M, Mattsson H, Prytz M, Hjertberg E, Tunek A, Miller-Larson A, Bratt-sand R. Uptake of a glucocorticoid budesonide, in rat airways and lung after inhalation and intravenous infusion. Eur Respir J 1994 7 (S18) 381. 

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. 

Budesonide is a high-potency glucocorticoid used in CD that has low systemic bioavailability when administered orally.23 The formulation releases budesonide in the terminal ileum for treatment of disease involving the ileum or ascending colon. Due to its reduced bioavailability, budesonide may prevent some long-term adverse effects in patients who have steroid-dependent IBD.23,24... 

Long-acting agents such as salmeterol and for-moterol have superseded short-duration bronchodila-tors such as albuterol and fenoterol. In addition, more potent, site-specific, rapid-onset glucocorticoids, such as fluticosone and budesonide, have superseded the delayed onset of action of less specific molecules such as budesonide. 

Beclomethasone dipropionate, and several other glucocorticoids—primarily budesonide and flunisolide and mometasone furoate, administered as aerosols—have been found to be extremely useful in the treatment of asthma (see Chapter 20). 

Budesonide is a potent synthetic analog of prednisolone that has high affinity for the glucocorticoid receptor but is subject to rapid first-pass hepatic metabolism (in part by CYP3A4), resulting in low oral bioavailability. A controlled-release oral formulation of budesonide (Entocort) is available that releases the drug in the distal ileum and colon, where it is absorbed. The bioavailability of controlled-release budesonide capsules is approximately 10%. 

Chronic lichenified eczema has been attributed to prolonged use of topical methylprednisolone aceponate and budesonide (strength and duration of therapy not stated) in a 26-year-old woman (425). Patch tests were positive for methylprednisolone aceponate and budesonide cream, but negative for all other topical glucocorticoids. 

Replacement of conventional glucocorticoids by oral pH-modified release budesonide in active and inactive Crohn s disease results of an open, prospective, multicenter trial. 

Systemic availability of inhaled glucocorticoids can be reduced in two ways. First, by using esters that reduced local absorption in the case of beclomethasone the dipropionate is used. Secondly, by using glucocorticoids that are extensively metabolized in the liver after absorption from the gut, such as fluticasone and budesonide. These strategies can be combined fluticasone is given as the ester fluticasone propionate. 

In healthy volunteers, high doses of both budesonide and fluticasone were readily absorbed after inhalation from a mete red-dose aerosol (2). Fluticasone is extensively metabolized by the liver, so measurable concentrations of parent drug in the systemic circulation reflect efficient absorption across the lung. Lower doses of these inhaled glucocorticoids also result in some systemic absorption, reflected in effects on the hypothalamic-pituitary-adrenal axis (3). 

The local adverse effects of inhaled glucocorticoids have been studied in a prospective, cross-sectional, cohort study in 639 asthmatic children using beclomethasone (721 micrograms/day) or budesonide (835 micrograms/ day) for at least one month (28). The local adverse effects included cough (40%), thirst (22%), hoarseness (14%), dysphonia (11%), oral candidiasis (11%), perioral dermatitis (2.9%), and tongue hypertrophy (0.1%). A spacer doubled the incidence of coughing. 

The long-term effects of budesonide on adrenal function have been assessed in 63 asthmatic children using budesonide 400 micrograms/day, nedocromil 16 mg/day, or placebo over 3 years (74). There were no differences in serum cortisol concentrations after ACTH stimulation between the three treatment groups, regardless of the time after ACTH administration or months of follow-up. Cumulative inhaled glucocorticoid exposure did not affect the serum cortisol response to ACTH or urinary free cortisol excretion at 3 years. 

Tixocortol pivalate is a marker for glucocorticoid contact allergy, as a positive patch test suggests established contact allergy to hydrocortisone, prednisolone, and their derivatives (95). A literature search via Medline from 1966 to May 2000 revealed only one patient hypersensitive to tixocortol pivalate and budesonide in a pilot study in 34 patients (10 with asthma, 13 with rhinitis, 11 with both) (96). From case reports, the prevalence of glucocorticoid-induced contact allergy has been estimated at 2.9-5%. 

Contact allergy to glucocorticoids is not rare in patients with atopic dermatitis. In patients with known contact allergy to budesonide, allergic skin reactions can also occur when inhaled forms of the drug are used, as shown by a randomized, double-bhnd, placebo-controlled study in 15 non-asthmatic patients with budesonide hypersensitivity on patch testing (101). In four of seven patients who used inhaled budesonide, there was reactivation of the 6-week-old patch test sites and they had new distant skin lesions. No flare-up reactions were observed in the other 11 patients (three had used inhaled budesonide and eight placebo for 1 week). None of the patients developed respiratory symptoms spirometry and peak expiratory flow rates remained normal. 

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