Therapeutic Glucocorticoid Agents

The primary glucocorticoids used pharmacologically are listed in Table 29-1. These drugs are either chemically identical to the naturally occurring hormones, or they are synthetic analogs of cortisol. The clinical choice of a particular agent depends on the problem being treated and the desired effect in each patient. 

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However, except when an increase in androgens is desirable, the use of ACTH as a therapeutic agent has been abandoned. Instances in which ACTH was claimed to be more effective than glucocorticoids were probably due to the administration of smaller amounts of corticosteroids... 

Numerous phase I clinical trials have already been conducted in the United States in which, using various protocols 156-160), the effects of taxol on solid tumors and on adult leukemia [a single study (767)] were evaluated. These studies have permitted determination of the doses (200-250 mg/m ) and the protocol (30 mg/m /day preceded by treatment with glucocorticoids and antihistamines) recommended for phase II evaluation, keeping in mind the main side effects caused by the solubilizing agent as well as leukopenic and neurotoxic effects. These phase II trials are currently underway, and only the results of one study (on a renal carcinoma) are presently available (762). It should be noted that one of the main obstacles to more rapid development of therapeutic uses of taxol is the very limited quantities of this drug available, for reasons already discussed. 

Glucocorticoids have a very wide application as antiinflammatory agents in therapeutics. The route by which they are administered depends largely on their relative freedom from dangerous side-effects. Many are used by topical application, but some are intrinsically more powerful than others and may only be used when weaker corticosteroids have failed. Different salts may be used for certain purposes. 

Bisphosphonates are the best therapeutic choice for patients with glucocorticoid-induced osteoporosis. Bisphosphonates generally produce greater BMD increases than do other agents used to treat osteoporosis. They increase spine (4.3%) and femoral neck (2.1%) BMD, but to a lesser extent than in bisphosphonate users who do not take glucocorticoids. They also likely reduce the risk of vertebral fractures by approximately 50%. ... 

Natural or synthetic steroids with cortisol-like effects are called glucocorticoids. Such compiiunds can act as anti-inllainmatory or immunosuppressive agents. Synthetic glucocorticoids have found therapeutic applications in a wide range of clinical situations, c.g. asthma and connective tissue disorders. 

THERAPEUTIC USES Many inflammatory skin diseases respond to topical or intralesional administration of glucocorticoids. Absorption varies among body areas the steroid is selected on the basis of its potency, the site of involvement, and the severity of the skin disease. Often, a more potent steroid is used initially, followed by a less potent agent. Twice-daily apphcation is sufficient, and more frequent apphcation does not improve response. In general, only nonfluorinated glucocorticoids should be used on the face or in occluded areas such as the axiUae or groin. 

It should be stressed, however, that all of the above therapeutics must be administered prior to the application of endotoxin to prevent the severe delayed circulatory failure as well as the induction of iNOS caused by endotoxin in vivo. For example, the administration of glucocorticoids or PAF receptor antagonists to rats at 90-180 min after an injection of endotoxin neither exerts beneficial hemodynamic effects nor inhibits the induction of iNOS (our unpublished observations). This supports the view that drugs that directly inhibit iNOS activity are useful tools in the treatment of various diseases associated with the induction of iNOS, whereas the use of agents that merely inhibit the induction of iNOS may be less useful. 

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