Corticosteroids oxidation

The outer layer or cortex of the adrenal gland is the source of a large group of sub stances known as corticosteroids Like the bile acids they are derived from cholesterol by oxidation with cleavage of a portion of the alkyl substituent on the D ring Cortisol IS the most abundant of the corticosteroids but cortisone is probably the best known Cortisone is commonly prescribed as an antiinflammatory drug especially m the treat ment of rheumatoid arthritis... 

Corticosteroids a chronic painless myopathy associated with the long-term use of corticosteroids is a particularly common example of drug-induced muscle disorder. It is almost certain that mild cases are overlooked because steroids are so frequently used to treat inflammatory myopathies such as polymyositis. Fluorinated steroids are particularly frequently implicated, and the incidence of drug-induced muscle disease is dose and time-related. The presence of muscle weakness can even complicate topical steroid therapy. Corticosteroid-induced myopathy is mediated via intramuscular cytosolic steroid receptors. The steroid-receptor complexes inhibit protein synthesis and interfere with oxidative phosphorylation. The myopathy is associated with vacuolar changes in muscle, and the accumulation of cytoplasmic glycogen and mitochondrial aggregations. 

The use of corticosteroids is controversial. While they may decrease the inflammation and endothelial cell adhesion seen with ACS, their use also has been associated with higher readmission rates for other complications. Tapered corticosteroids, nitric oxide therapy, and L-arginine are being evaluated for use in ACS in studies.34,36... 

Argininosuccinate lyase (AL) (Fig. 40-5 reaction 4) cleaves argininosuccinate to form fumarate, which is oxidized in the tricarboxylic acid cycle, and arginine, which is hydrolyzed to urea and ornithine via hepatic arginase. Both AL and arginase are induced by starvation, dibutyryl cyclic-AMP and corticosteroids. 

Furuncles (boils) are caused by staphylococci. Fusidic acid is very effective against boils. Hydrocortisone is a lov/-potency corticosteroid. Aciclovir (antiviral) is indicated for the treatment and prophylaxis of herpes infections. Promethazine is an antihistamine cream and zinc oxide acts as a barrier v/hen used in creams. 

In neutral medium, and in the presence of air and cupric acetate, the ketol group is first oxidized into a ketoaldehyde that then condenses with o-phenylenediamine to produce a quinoxaline derivative. This derivative absorbs strongly in the near-UV range [82], with all of the corticosteroids affording equivalent sensitivity levels [72]. 

System (2) has been described for the assay of corticosteroids (cortisone, hydrocortisone, prednisone, and prednisolone) in urine [141]. Prior to introduction into the GC system, the sample was eluted with 2 1 ethyl acetate-methanol, the extracts evaporated to dryness, and then oxidized with sodium bismuthate. Used in the method was a silanized column (132 cm X 5 mm) containing 2,2-dimethylpropane-l,3-diol adipate (0.65%) supported on celite, and operated at 230°C. The carrier gas was argon, and the detector used strontium 90-ionization. The standard deviation was 3.5 % (based on 47 determinations). 

Betamethasone is well absorbed after oral administration to be extensively bound to plasma proteins in humans, dogs, cows, and rats. Its metabolism does not differ of the other corticosteroids, involving oxidation of the 11 -hydroxyl group to ketone, reduction of the ketone group at the position C-20 to give the corresponding alcohol, and hydroxylation at the C-6 position and loss of the C-17 side chain to give 17-oxosteroids. 

Following solid-phase extraction, all extracts are adjusted in the pH range 7-7.5, and submitted to additional cleanup on an immunoaffinity column containing a mixture of dexamethasone- and prednisolone-specific gels. Column washing is performed with water, while elution of the analytes with 3 ml methanol/water (80 20). Aliquots of the eluates are submitted to oxidative reaction with pyridin-ium chlorochromate, and the oxidized corticosteroid derivatives are then analyzed by gas chromatography-mass spectrometry under the conditions shown in Table... 

The bismethylenedioxy group (BMD) [ (49)] represents the most suitable protecting group for the dihydroxyacetone side chain of corticosteroids. This group is stable to lead tetraacetate, brief heating with hydrochloric acid in acetic acid,108 or with sulfuric acid in methanol18 and to Jones oxidation.189... 

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