Synthetic corticosteroids

Brand Name(s) Cormax, Olux, Temovate Cfiemical Class Corticosteroid, synthetic... 

Metyrapone is used to block the mitochondrial 1 ip-hydroxylase in the corticosteroid synthetic pathway and is administered to evaluate hypothalanuc-pituitary-adrenal axis function. Which of the following results is most likely from this overnight diagnostic test in a healthy individual ... 

Because all known therapeutic effects ofACTH can be achieved with corticosteroids, synthetic steroid hormones generally are used therapeutically instead ofACTH. A synthetic derivative of ACTH comprised of the first 24 amino acids of the natural hormone, cosyntropin ( cortrosyn, syn-acthen), is used principally in the diagnostic assessment of the HPA axis. In the standard cosyntropin test, cosyntropin is used at the considerably supraphysiological dose of 250 pg to maximally stimulate adrenocortical steroidogenesis. Cosyntropin is readily absorbed from... 

Efforts toward producing synthetic steroids, particularly cortisol, expanded during World War II to enable researchers to explore the possibiUty of medicinal appHcations of corticosteroids. In 1948, the discovery that cortisone dramatically alleviates the symptoms of arthritis led to intensive research on the antiinflammatory properties of corticosteroids. The development of partial and total syntheses for the commercial preparation of cortisone, alternative methods for producing cortisone, and the search for more potent antiinflammatory analogues gready stimulated both academic and industrial steroid research. 

There are several hundred reported NF-kB inhibitors (see www.nf-kb.org for a complete and updated list). These inhibitors include natural products, chemicals, metabolites, and synthetic compounds. A large majority of these products, in particular commonly used antiinflammatory drugs such as corticosteroids and the nonsteroidal antiinflammatory drugs (NSADDs) aspirin, sulindac, ibuprofen and sulphasalazine, have the ability to partially inhibit NF-kB activity in cell culture. However, the precise mechanism of action and the specific molecular targets of most of these inhibitors remain unclear. 

Corticosteroids are hormones secreted from the adrenal cortex. These hormones arise from the cortex of the adrenal gland and are made from the crystalline steroid alcohol cholesterol. Synthetic forms of the natural adrenal cortical hormones are available The potent antiinflammatory action of the corticosteroids makes these drugs useful in the treatment of many types of musculoskeletal disorders. The corticosteroids are discussed in Chapter 50. 

We describe below the use of halloysite nanotubules for entrapment and the subsequent release of three drugs Nifedipine (anti-anginal), Furosemide (anti-hypertension and diuretic), and Dexamethasone (synthetic corticosteroid). To increase the loading of these poorly soluble drugs in the tubules, we loaded them into a water-alcohol co-solvent solution (0, 10, and 50% ethanol). 

Tazarotene (Tazorac) is a synthetic retinoid that is hydrolyzed to its active metabolite, tazarotenic acid, which modulates keratinocyte proliferation and differentiation. It is available as a 0.05% or 0.1% gel and cream and is applied once daily (usually in the evening) for mild to moderate plaque psoriasis. Adverse effects are dose- and frequency related and include mild to moderate pruritus, burning, stinging, and erythema. Application of the gel to eczematous skin or to more than 20% of body surface area is not recommended because this may lead to extensive systemic absorption. Tazarotene is often used with topical corticosteroids to decrease local adverse effects and increase efficacy. 

Halohydrins biological activity of semi-synthetic corticosteroids... 

Corticosteroids are produced by the adrenal glands, and display two main types of biological activity. Glucocorticoids are concerned with the synthesis of carbohydrate from protein and the deposition of glycogen in the liver. They also play an important role in inflammatory processes. Mineralocorticoids are concerned with the control of electrolyte balance, promoting the retention of Na+ and CC, and the excretion of K+. Synthetic and semi-synthetic corticosteroid drugs are widely used in medicine. Glncocorticoids are primarily nsed for their antirhenmatic and anti-inflammatory activities, and mineralocorticoids are nsed to maintain electrolyte balance where there is adrenal insufficiency. 

The a- and /8-globulins of the plasma also form an important group of binding proteins and a number of them have been isolated and found to have a high affinity, but relatively low capacity, for a variety of endogenous and chemically related synthetic compounds. Westphal (W7) has reviewed the extensive literature on the interaction of corticosteroids... 

Steroids represent another typical class of doping substances. The determination of endogenous steroids (e.g., testosterone), synthetic anabolic steroids, their esters and their conjugates, and corticosteroids by HPLC-MS has been recently object of an exhaustive review [115] and will not be further discussed here. 

A wide range of pharmaceutical substances are derived from animal sources (Table 1.10). Many are protein-based and detailed description of products such as insulin and other polypeptide hormones, antibody preparations, vaccines, enzymes, etc., have been deferred to subsequent chapters. (Many of the therapeutic proteins are now also produced by recombinant DNA technology. Considerable overlap would have been generated had a product obtained by direct extraction from native sources been discussed here, with further discussion of a version of the same product produced by recombinant DNA technology at a later stage.) Non-proteinaceous pharmaceuticals originally derived from animal sources include steroid (sex) hormones, corticosteroids and prostaglandins. A limited discussion of these substances is presented below, as they will not be discussed in subsequent chapters. Most of these substances are now prepared synthetically. 

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 ... 

Betamethasone Synthetic corticosteroid, displays glucocorticoid activity, lacks mineralocorticoid activity Use mainly as anti-inflammatory and immunosuppressive effect... 

Fludrocortisone acetate Synthetic corticosteroid with some glucocorticoid and potent mineralocorticoid activity Administered orally to treat primary adrenal insufficiency... 

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