Glucocorticoids, naming

Trihydroxy-6,16a-dimethyl-2 -phenyl-2 H-pregna-2,4,6-trieno[3,2-c] -pyrazol-20-one-21-acetate, commonly named cortivazol (696), has been used since 1962 by Merck Co. as a glucocorticoid (B-76MI40404). Tricyclic pyrazoles (697) have been found to possess antiarrhythmic and antiinflammatory activities (76JHC545). 

Melanocortin peptides are potent anti-inflammatory agents displaying beneficial effects in diseases ranging from cardiovascular to arthritis to obesity to name a few. Within an inflammatory context, they have the ability to switch off early production of cytokines and at later stages they increase levels of anti-inflammatory proteins that lead to the resolution of the host inflammatory response potentially restoring homeostasis to the tissue. They could eventually be viewed as an alternative to glucocorticoids, as their mode of action often resembles that seen... 

Recently, Tse et al. [73] and Orlowski et al. [74] have cloned a third isoform of Na /H exchanger (named NHE-3). The inferred 832-amino acid sequence of rabbit NHE-3 is 41% identical with NHE-1, 44% identical with NHE-2, and has a similar secondary structure. In contrast to NHE-1 and NHE-2, NHE-3 is only expressed in epithelia in intestine and kidney. Moreover, administration of glucocorticoids, which stimulates transport activity of the apical Na /H" exchanger in rabbit intestine, increased levels of NHE-3 transcripts but did not affect NHE-1 or NHE-2 [75]. Taken together, these results suggest that NHE-3 may encode a resistant-type Na /H exchanger of epithelia. A fourth Na /H exchanger isoform (NHE-4) is preferentially expressed in stomach [74]. 

Brand Name(s) Beclovent, Beconase, Beconase AQ, Qvar, Vancenase, Vancenase AQ, Vancenase AQ DS, Vanceril, Vanceril DS Cfiemical Class Glucocorticoid, synthetic... 

Brand Name(s) AK-Pred, Cotolone, Depo-Predate, Hydeltrasol, Inflamase Forte, Infla-mase Mild, Key-Pred, Key-Pred SP, Orapred, Predacort 50, Predaject-50, Predate-50, Pred Forte, Pred-Ject-50, Pred Mild, Prednisolone Acetate, Prelone Chemical Class Glucocorticoid, synthetic... 

Brand Name(s) (Triamcinolone hexacetonide) Aristospan Cfiemical Class Glucocorticoid, synthetic... 

Clinically, ACTH stimulation of the adrenals is used diagnostically to detect adrenal insufficiency plasma cortisol levels are measured before and 60 minutes following an intravenous injection of cosyntropin. Adrenocortical insufficiency is known as Addison s disease Addison s classic description, in 1855, namely general debility, remarkable feebleness of the heart, irritability of the stomach, and a peculiar change of the colour of the skin , summarizes the clinical features of this disease, which is uniformly fatal if undetected and untreated. Therapeutically, corticotropin therapy has been essentially abandoned in favor of the direct administration of glucocorticoids. However, ACTH is still rarely used in the treatment of the infantile spasm seizure disorder. 

The two main classes of adrenal corticosteroids are properly known as glucocorticoids and mineralocorticoster-oids. The former are often known by shorter names and are commonly referred to as glucocorticoids , corticosteroids , corticoids , or even simply steroids the latter are often referred to as mineralocorticoids . Here we shall use the terms glucocorticoids and mineralocorticoids . When referring to both we shall use the term corticosteroids . 

Fig. 10. The structure of mouse DNA containing the integrated mouse mammary tumour provirus. The integrated viral DNA can be present in many copies. The provirus contains two long terminal repeat sequences, LTR, only one of which (left) is shown in detail here. Each LTR contains sequences termed U3, R and U5 (for details, see Ref. 67). Interspersed between the LTRs are the genes named gag, pol and env, encoding viral coat proteins, reverse transcriptase and envelope proteins, respectively. The glucocorticoid-binding sequence is represented by the black box, and the transcriptional initiation area is indicated by the hatched box.

The secretion of epinephrine by the adrenal medulla is controlled directly by nerve impulses and also by the other stress hormones, namely, corticosteroids. This is illustrated in Figure 16.11. Nerve impulses have a major stimulatory effect on tyrosine and dopamine hydroxylases, whereas glucocorticoids have a major effect on phenylethanolamine methyltransferase. Tyrosine hydroxylase is considered the rate-controlling enzyme in the biosynthesis... 

There are two main groups of corticosteroids, namely mineralocorticoids and glucocorticoids, though only the latter group can act locally and systemically. 

MT gene expression is largely regulated at the transcriptional level. Enhanced MT expression may also be attributed to MT gene amplification. However, the specific mechanism by which MT gene expression is regulated in vivo in response to metal exposure is as yet unclear. In addition to metals, a number of other stimuli are known to induce MT, namely glucocorticoids, cytokines, oxidative stress, and a variety of chemicals. 

Melanocortins. This is a generic name for the peptide hormones, melanotropin and corticotropin, (ACTH, adrenocorticotropic hormone), because both hormones are formed in the anterior pituitary gland from the same melanocortin precursor. Melanotropin controls melanocyte growth and pigmentation. Corticotropin stimulates the production of glucocorticoids and mineralocorticoids, such as aldosteron, in the adrenal cortex. The Melanocortin-pathway is somehow involved in the control of appetite and body weight. 

In several instances, the steroid hormones were named for their most prevalent biologic activity. Thus, the steroids found to cause mobilization of glucose were called glucocorticoids. Min-eralocorticoids were those steroids that regulated the balance of the minerals sodium and potassium. 

Mycophenolate has also been studied in various chronic inflammatory disorders, such as rheumatoid arthritis, pemphigus vulgaris, and psoriasis. In 70 patients with chronic active Crohn s disease, mycophenolate plus glucocorticoids produced benefit on disease activity comparable to azathioprine plus glucocorticoids (7). Two of the 35 patients randomized to mycophenolate had significant adverse effects that required drug withdrawal, namely rashes and vomiting. 

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