Corticosteroids—glucocorticoids drug administration

Hypersensitivity reactions to etoposide or teniposide usually occur within minutes after intravenous administration, and are probably related to release of vasoactive substances by basophils and/or mast cells. Several reports have suggested that premedication with an antihistamine and/or a corticosteroid may prevent further hypersensitivity reactions, even in patients with a history of previous reactions. However, this strategy should not be followed when patients have had severe hypersensitivity reactions, such as long-lasting bronchospasm or severe hjrpotension (130,131). Etoposide was successfully restarted in 78% of patients who had had a hypersensitivity reaction, especially when the drug was infused at a slower rate after premedication with an antihistamine and/or a glucocorticoid (132). 

There are three aerosolized corticosteroid preparatioias available in MDI formulation for administration to horses via the Equine AeroMask beclometasone dipropionate, fluticasone propionate and flunisolide (Table 16.2). In terms of the relative potency, fluticasone is more potent than beclometasone, which is more potent than flunisolide, which is equipotent to triamcinolone. Using dexamethasone as the standard (1.0), the relative glucocorticoid receptor affinity of the common corticosteroids is flunisolide 1.9, triamcinolone 2.0, beclometasone (active metabolite) 13.5 and fluticasone propionate 22.0 (Barnes et al 1998). The pulmonary residence time of the aerosolized corticosteroids is determined by the lipophilicity of each drug. Flunisolide has intermediate water solubility (lOmg/ml), simitar to... 

Treatment of these problems is by substituting another insulin species which does not cross-react with the antibodies, by desensitization, or by local or systemic administration of glucocorticoids. If a severe allergic reaction occurs, the drug has to be discontinued and the patient treated with the usual agents (e.g. adrenaline, antihistamines or corticosteroids). Patients who have experienced severe systemic allergic symptoms should be skin-tested with another insulin preparation before its initiation. Desensitization procedures may permit resumption of insulin administration. 

Cortisone acetate or hydrocortisone usually is the corticosteroid of choice for replacement therapy in patients with adrenocortical insufficiency, because these drugs have both glucocorticoid and mineralocorticoid properties. Following oral administration, cortisone acetate and hydrocortisone acetate are completely and rapidly deacetylated by first-pass metabolism (37). Much of the oral cortisone, however, is inactivated by oxidative metabolism (Fig. 33.9) before it can be converted to hydrocortisone in the liver. The pharmacokinetics for hydrocortisone acetate is indistinguishable from that of orally administered hydrocortisone. Oral hydrocortisone is completely absorbed, with a bioavailability of greater than 95% and a half-life of 1 to 2 hours (23). The metabolism of hydrocortisone (Fig. 33.9) has been previously described. Cortisone acetate is slowly absorbed from IM injection sites over a period of 24 to 48 hours and is reserved for patients who are unable to take the drug orally. The acetate ester derivative demonstrates increased stability and has a longer duration of action when administered by IM injection. Thus, smaller doses can be used. Similarly, hydrocortisone may be dispensed as its 21-acetate (hydrocortisone acetate), which is superior to cortisone acetate when injected intra-articularly. Systemic absorption of hydrocortisone acetate from intra-articular injection sites usually is complete within 24 to 48 hours. When administered intrarectally, hydrocortisone is poorly absorbed (38,39). 

Although short-term administration of corticosteroids are unlikely to produce harmful effects, these drugs, when used for longer than brief periods, can produce a variety of devastating effects, including glucocorticoid-induced adrenocortical insufficiency, glucocorticoid-induced ... 

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