"THE MATERIAL PRESENTED HERE ONLY ENHANCES CLASSROOM TEACHING AND IN NO WAY SHOULD BE CONSTRUED AS REPLACING IT. THE INSTRUCTOR is not responsible for any problems and SHOULD BE CONSULTED AT THE EARLIEST IN CASES OF DIFFICULTY, CONFUSION, or PLAIN DISILLUSIONMENT. VISIT THE HOMEPAGE FOR INFORMATION PERTAINING TO REACHING HIM/HER"
|Topics of Special Interest|
|Mechanism of Action|
The adrenal gland secretes numerous steroids of which aldosterone and hydrocortisone are the major ones. The structures of aldosterone and hydrocortisone are
The steroids secreted are called adrenocorticoids. Aldosterone possesses mineralocorticoid activity while hydrocortisone is a glucocorticoid.
Mineralocoriticoid activity is related to retaining salt, NaCl. Mineralocorticoids maintain electroylte balance by retaining Na+ and promoting K+ excretion.
Glucocorticoids have numerous physiological activity. They are important for the biosynthesis and metabolism of carbohydrates, proteins and lipids. They are also involved in immune responses. This statement itself suggests the phenomenal importance of these drugs. In addition, glucocorticoids possess anti-inflammatory activity. This activity has become so important that we now refer to only the anti-inflammatory activity of glucocorticoids and conveniently forget the systemic action of these hormones.
Adrenocorticoids are used in:
Addison’s disease : decreased production of adrenocorticoids e.g., in TB
Adrenalectomy : elimination of adrenal cortex
Cushing’s syndrome : hyperadrenalism e.g., tumors
Decreased production of adrenocorticoids leads to reduction in resistance to trauma, increased sensitivity to pain.
Biochemical Mechanism of Action
Anti-inflammatory Activity of Glucocorticoids
Cortisol induces the production of lipocortin and related proteins by increasing gene expression through the glucocorticoid receptor mechanism. Lipocortin inhibits the activity of phospholipase A2 which liberates arachidonic acids and leads to the production of eicosanoids/prostaglandins and leucotrienes which are the mediators of inflammation. Because glucocorticoids have systemic activity they are not used as systemic anti-inflammatory drugs. Hence we find these primarily in topical applications such as creams and ointments.
The mineralocorticoid action of these steroidal hormones relates to synthesis of aldosterone – induced protein which is a permease that regulates cell permeability to Na+ and maintain Na+ influx (elevated Na+-K+-ATPase Pump).
The structure of glucocorticoids determine their biological activity. Innumerable molecules have been studied to reduce the mineralocorticoid activity and retain the glucocorticoid activity. Some drugs that are currently available in the market are:
cortisol 1 1
aldosterone 800 1
fludrocortisone 800 5-40
11-deoxycorticosterone 40 0
prednisolone 0.6 4
6a-methyl prednisolone 0 5
betamethasone 0 5-100
dexamethasone 0 10-35
Flumethasone 0 > 100
Based on these and other studies we can generalize the following guidelines for anti-inflammatory activity of glucocorticoids:
[school of pharmacy] [department
of medicinal chemistry]
[links to sites of interest and download center] [instructions for downloading and installing software]
©2000 VCU School of
Revised: October 24, 2000
Questions or Comments : Dr. Umesh R. Desai