Steroids prolonged therapy effects

Glucocorticoids are available in a wide range of preparations, so that they can be administered parenterally, orally, topically, or by inhalation. Obviously the oral route is preferred for prolonged therapy. However, parenteral administration is required in certain circumstances. Intramuscular injection of a water-soluble ester (phosphate or succinate) formed by esterification of the C21 steroid alcohol produces peak plasma steroid levels within 1 hour. Such preparations are useful in emergencies. By contrast, acetate and tertiary butylacetate esters must be injected locally as suspensions and are slowly absorbed from the injection site, which prolongs their effectiveness to approximately 8 hours. 

Therapeutic use is seldom appropriate because the peptide hormone has to be injected selective glucocorticoid action (without mineralocorticoid effect) cannot be obtained, and clinical results are irregular. Corticotropin can not be relied on to restore adrenal cortisol output when a steroid is being withdrawn after prolonged therapy, as it does not restore function in the suppressed hypothalamic/pituitary part of the HPA axis. 

The major effect of prolonged therapy is adrenal atrophy. In addition, corticosteroids, which have a similar structure to reproductive steroids (e.g., estrogen and testosterone), can feed back on the production of reproductive steroids. This can result in decreased sperm maturation, in particular, and infertility. 

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. 

In about one-fourth to one-third of the patients receiving prolonged steroid therapy, the hyperglycemic effects... 

L E. Recovery from prolonged steroid therapy is slow, and the withdrawal may be unpleasant. The patient may be reluctant to reduce the dose of steroid because of its salutary effects on the psyche. Tapering the dose of steroid is important in steroid withdrawal however, the patient may temporarily require a dose increase during periods of heightened stress. 

Because side effects can complicate the use of corticosteroids, a careful history and certain tests may be advisable, particularly if a patient may require prolonged ocular therapy. Steroids should be used with great caution in patients with diabetes mellitus, infectious disease, chronic renal feilure, congestive heart feilure, and systemic hypertension. Systemic administration is generally contraindicated in patients with peptic ulcer, osteoporosis, or psychoses. Topical steroids should be used with caution and only when necessary in patients with glaucoma. 

Unwanted effects generally follow prolonged adrninistration and virtually do not occur with 1 or 2 doses though some occur with a few days use, e.g. spread of infection. The undesired effects recounted below should never be experienced in replacement therapy, but are sometimes unavoidable when the steroid is used as pharmacotherapy. Obviously, the nature of unwanted effects depends on the choice of steroid. Fludrocortisone (mineralo-corticoid) in ordinary doses does not cause osteoporosis and prednisolone (glucocorticoid) does not normally cause oedema. 

Short-term, intensive pulse doses of corticosteroids, similar to those used in acute exacerbations, initially may decrease disability, but prolonged steroid therapy has no established effects on the progression of disease. If progression continues while a patient is on a diseasemodifying agent, an immunosuppressive agent may be tried. 

Optimal steroid therapy for PVR would maintain therapeutic levels in the vitreous for a prolonged period at present this can only be achieved by prohibitively high systemic dosing or intravitreal injections (which do not maintain constant drug levels). A sustained release device that maintains constant therapeutic intravitreal levels with minimal systemic exposure may prove useful in the clinical management of PVR, although the potential for ocular effects such as elevation of intraocular pressure and cataract cannot be ignored. 

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