INDEX with corticosteroids

Theophylline is also considered an alternative to inhaled corticosteroids for the treatment of mild persistent asthma however, limited efficacy compared to inhaled corticosteroids, a narrow therapeutic index with life-threatening toxicity, and multiple clinically important drug interactions have severely limited its use. Theophylline causes bronchodilation through inhibition of phosphodiesterase and antagonism of adenosine and appears to have anti-inflammatory and immunomodulatory properties as well.36... 

Other antileprotics include ethionamide and pro-thionamide. Thalidomide (see Index), despite its notorious past, still finds a use with corticosteroid in the control of allergic lepromatous reactions. 

Osteoporosis is also common in those on long-term corticosteroid therapy (for example patients with autoimmune hepatitis or coexisting inflammatory bowel disease). Patients with chronic liver disease may also have other risk factors for osteoporosis related to their disease state. These include vitamin D deficiency, excessive alcohol consumption, poor diet, physical inactivity and low body mass index. Oestrogen deficiency in the postmenopausal stage further increases the risk. 

In asthmatic human patients, fluticasone propionate improves asthma symptoms and parameters, improves pulmonary function and reduces pulmonary inflammation and airway reactivity (Barnes et al 1998). Regular fluticasone reduces or eliminates the need for rescue 2 agonist therapy and produces progressive improvement in airway reactivity and pulmonary function. In clinical studies, equivalent efficacy is demonstrated with one-quarter of the dose of fluticasone compared with flunisolide and budesonide, and equivalent efficacy is demonstrated with one-half of the dose of fluticasone compared with beclometasone. Adrenal function is less affected by fluticasone propionate at therapeutic doses than with beclometasone, flunisolide or budesonide. Although all aerosolized corticosteroids are considered safe, fluticasone has the least potential for adverse systemic effects and has the most favorable therapeutic index. 

Category B medicines of great social and therapeutic value (treatment of heart diseases, rheumatoid arthritis, antibiotics, corticosteroids, antipsychotics). The co-payment (with a maximum amount of 355 Belgian Francs [BF]) is 25 percent for normal insured people and 15 percent for people with a special tariff (pensioners, widows, orphans and invalids). This maximum is adapted each year to the national index figures. 

Simple alkyl esters also proved virtually inactive. Consequently, the 17/3-chloromethyl ester was held constant and 17a-carbonates with different substituents on the steroid skeleton were varied for further investigation. Loteprednol etabonate, and some of the other soft steroids, provided a significant improvement of the therapeutic index determined as the ratio between the anti-inflammatory activity and the thymus involution activity (114, 117,118). Furthermore, binding studies using rat lung cytosolic corticosteroid receptors showed that some of the compounds approach and even exceed the binding affinity of the most potent corticosteroids known. 

Modification of the pharmacokinetics through structural alterations has provided several new steroids with a better GR affinity and therapeutic index and a lower bioavailability than the older drugs (Fig. 33.14). The new inhaled/intranasal glucocorticosteroids like mometasone furoate, budesonide and fluticasone propionate are more lipophilic than those used in oral and systemic therapy and have greater affinity for the GR than does dexamethasone as a consequence of their greater lipophilicity (43). Several of the topical corticosteroids, such as mometasone furoate, BDP, triamcinolone acetonide, and flunisolide, were reintroduced as inhalation and intranasal dosage forms for treatment of respiratory diseases (e.g., asthma or rhinitis). Inhaled budesonide and flunisolide are readily absorbed from the airway mucosa into the blood and are rapidly biotransformed in the liver into inactive metabolites. Mometasone furoate and fluticasone propionate are very potent anti-inflammatory steroids with an oral bioavailability of less than 1%. Obviously, the risk of systemic side effects for these newer corticosteroids is greatly reduced when compared with ... 

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