Adrenocortical steroids and their synthetic analogues Mechanisms of action Actions: mineralocorticoid, glucocorticoid Individual adrenal steroids Pharmacokinetics Dosage schedules Choice of adrenal steroid Adverse effects of systemic pharmacotherapy Adrenal steroids and pregnancy Precautions during chronic therapy: treatment of intercurrent illness Dosage and routes of administration Indications for use Uses: replacement therapy, pharmacotherapy Withdrawal of pharmacotherapy . Inhibition of synthesis of adrenal steroids. Competitive antagonism . Adrenocorticotrophic hormone (ACTH) (corticotropin) . | SECTION 8 ENDOCRINE SYSTEM METABOLIC CONDITIONS This page intentionally left blank 34 n -j O z oo Adrenal corticosteroids antagonists corticotropin SYNOPSIS Adrenocortical steroids and their synthetic analogues Mechanisms of action Actions mineralocorticoid glucocorticoid Individual adrenal steroids Pharmacokinetics Dosage schedules Choice of adrenal steroid Adverse effects of systemic pharmacotherapy Adrenal steroids and pregnancy Precautions during chronic therapy treatment of intercurrent illness Dosage and routes of administration Indications for use Uses replacement therapy pharmacotherapy Withdrawal of pharmacotherapy Inhibition of synthesis of adrenal steroids Competitive antagonism Adrenocorticotrophic hormone ACTH corticotropin By 1936 numerous steroids were being crystallised from cortical extracts but not enough could be obtained to provide supplies for clinical trial. In 1948 cortisone was made from bile acids in quantity sufficient for clinical trial and the dramatic demonstration of its power to induce remission of rheumatoid arthritis was published the following year. In 1950 it was realised that cortisone was biologically inert and that the active natural hormone is hydrocortisone cortisol . Since then an embarrassingly large number of synthetic steroids has been made and offered to the clinician. They are derived from natural substances chiefly plant sterols the constitutions of which approach most nearly to that of the steroids themselves. A principal aim in research is to produce steroids with more selective action than hydrocortisone which induces a greater variety of effects than desired in any patient who is not suffering from adrenal insufficiency. About the same time as cortisone was introduced corticotropin became available for clinical use. In 1855 Dr Thomas Addison assisted in his observations by three colleagues published his famous monograph On the constitutional effects of disease on the suprarenal capsules Addison s disease . It was .