Mineralocorticoid potency

Systemic Anti- inflammatory Potency Mineralocorticoid Potency Duration of Biologic Activity (hours) Elimination Half-Life (hours)... 

The actions of the synthetic steroids are similar to those of cortisol (see above). They bind to the specific intracellular receptor proteins and produce the same effects but have different ratios of glucocorticoid to mineralocorticoid potency (Table 39-1). 

Compound Glucocorticoid potency relative tohydrocortisone Mineralocorticoid potency Equivalent doses (mg)... 

A natural extension of corticoid research involved examination of compounds containing both a 9a-fluoro group and a double bond between positions 1 and 2. Triamcinolone (9-fluoro-11 (3, 16a, 17, 21-tetrahydroxypregna-1,4-diene-3,20-dione), introduced in 1958, combines the structural features of a A -corticoid and a 9a-fluoro corticoid (Fig. 33.10). As mentioned previously, the 9a-fluoro group increases the anti-inflammatory potency, but it also markedly increases the mineralocorticoid potency. This is undesirable if the drug is to be used internally for the treatment of rheumatoid arthritis. By inserting a 16a-hydroxy group into the molecule, one can decrease the mineralocorticoid activity. 

Methylated Glucocorticoids. The preparation of 2a-methyl-9a- uorocortisol has been reported (76). This compound shows enhanced glucocorticoid activity and greatiy enhanced mineralocorticoid activity, so much that it surpasses aldosterone (19) ia sodium-retaining and potassium-excreting potency. Attention was then turned to the preparation of 6-methylated corticoids... 

Various synthetic corticosteroids have also been developed. Some display greater potency than the native steroids, while others exhibit glucocorticoid activity with little associated mineralocorticoid effects, or vice versa. The major glucocorticoids used clinically are synthetic. They are usually employed as ... 

Dexamethasone has a high potency and has minimal mineralocorticoid activity. It is rapidly absorbed after oral administration with peak effects within 1-2 hours. The duration of action is about 3 days after oral administration and up to weeks after injections of the sodium phosphate derivative. This long... 

Additional double bonds. A -componnds (where A indicates the position of a double bond) were introduced, like prednisone (3.7), a A -ll-ketone, and prednisolone, its 11-hydroxy analogne. Changing the geometry of the A ring increased the potency without augmenting mineralocorticoid activity. 

The approximate potency of various mineralocorticoids relative to cortisone is shown in Table 1. 

On the hypothesis that the side chain could perhaps be stabilized against such metabolic inactivation by an appropriately placed but otherwise chemically inert substituent, some analogues of cortisone containing a 16a-methyl group were synthesized by Arth et al. [20] in the expectation that the 16a-methyl substituent would enhance potency by protecting the 20-ketone from metabolism. Ultimately, these authors prepared 9-fluoro-16a-methylprednisolone which was the first derivative of fluorocortisol with markedly increased anti-inflammatory activity that was devoid of mineralocorticoid activity. This latter fact supports the concept that it is the presence of 16a-substituents that prevents binding to the mineralocorticoid receptor. Dexamethasone has become Merck s principal marketed anti-inflammatory steroid. 

The relative potencies for glucocorticoid and mineralocorticoid (sodium-retaining) effects which are shown in Table 34.1 are central to the choice of agent in relation to clinical indication. 

Corticosteroids should only be used during acute exacerbations of ulcerative colitis. The total duration of therapy should not exceed 4 to 8 weeks. Many different corticosteroids are available and differ in anti-inflammatory potency and mineralocorticoid activity (Table 38-2). Choosing a corticosteroid and route of administration depends on the clinical presentation. 

Drug Route Equivalent antiinflammatory dose (mg) Anti-inflammatory potency Mineralocorticoid activity... 

Mineralocorticoid refers to those steroids that regulate salt homeostasis (sodium conservation and potassium loss) and extracellular fluid volume.Aldosterone is the most potent naturally occurring mineralocorticoid and is synthesized exclusively in the zona glomerulosa region of the adrenal cortex. This zone uniquely contains the enzyme aldosterone synthase, an obligatory enzyme in the synthetic pathway to aldosterone. Other adrenocortical steroids that have mineralocorticoid properties with varying degrees of potency include DOC, 18-hydroxy-DOC, corticosterone,... 

Hydrocortisone is an adrenocorticoid with both glucocorticoid and mineralocorticoid properties. It is a weak antiinflammatory agent but a potent mineralocorticoid, having potency similar to that of cortisone and twice that of prednisone. Hydrocortisone (or cortisone) is usually the drug of choice for replacement therapy in patients with adrenal insufficiency. It is usually not used for immunosuppressant... 

Corticosteroids traditionally are divided into mineralocorticoids and glucocorticoids according to their relative potencies in Na retention and effects on carbohydrate metabolism i.e., hepatic deposition of glycogen and gluconeogenesis) In general, potencies of steroids to sustain life in adrenalectomized animals closely parallel their mineralocorticoid activity, while potencies as antiinflammatory agents closely parallel their effects on glucose metabolism. The effects on Na" retention and the carbohydrate/anti-inflammatory actions are not closely related and reflect selective actions at distinct receptors. 

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