Dexamethasone potency

The natural compounds cortisol [50-23-7], cortisone [53-06-5], and corticosterone [50-22-6] vary only slightly in stmctures and pharmacologic properties (see Steroids). The synthetic analogues inmore modem practice, prednisolone [52438-85-4], dexamethasone [50-02-2], triamcinolone [124-94-7], and betamethasone have greater antiinflammatory potency, and their effects on sodium retention tend to be less severe. 

Synthetic steroid with strong glucocorticoid-agonistic activity. Dexamethasone is over 10 times more potent than cortisol due to a higher binding affinity for glucocorticoid receptor and a decreased clearance rate of the compound. Due to its potency, dexamethasone is widely used in the clinics for the treatment of inflammatory diseases. 

Suspension. If the drug is not sufficiently soluble, it can be formulated as a suspension. A suspension may also be desired to improve stability, bioavailability, or efficacy. The major topical ophthalmic suspensions are the steroid anti-inflammatory agents prednisolone acetate, dexamethasone, fluorometholone, and rimex-olone. Water-soluble salts of prednisolone phosphate and dexamethasone phosphate are available however, they have a lower steroid potency and are poorly absorbed. 

Two further communications [31,32] reported that prednisolone stearoylglycollate, in substantial doses, was the least potent anti-inflammatory steroid (among the representative series studied) with respect to pituitary-adrenal inhibition. The order of increasing suppressive potency in this test was prednisolone stearoylglycollate, prednisolone, triamcinolone, dexamethasone, betamethasone. Techniques used in the comparative evaluations included the metyrapone test and gas-liquid chromatography. 

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... 

Trichlormethiazide is often given in combination with dexamethasone because in this way effects can be achieved with a minimum dosage of trichlormethiazide, since tire two drugs are complementary in their action. Studies in humans and experimental animals have shown that trichlormethiazide presents a favorable pattern of lower potassium excretion than the other thiazides. The clinically determined saluretic potency of trichlormethiazide was estimated to be 10-20 times lower than that of hydrochlorothiazide and 100-200 times lower than that of chlorothiazide this results in decrease in the incidence of hypokalemic manifestations. 

Miyabo, S., T. Nakamura, S. Kuwazima, and S. Kishida. 1981. Acomparison of the bioavailability and potency of dexamethasone phosphate and sulphate in EianJ. Clin. Pharmacol20 277-282. 

Cevc, G., and G. Blume. 2004. Hydrocortisone and dexamethasone in very deformable drug carriers have increased biological potency, prolonged effect, and reduced therapeutic dosage. Biochim Biophys Acta 1663 61. 

Bleomycin Bleomycin is incompatible and loses its potency if it is administered with solutions of benzylpenicillin sodium, carbenicillin, cephazolin or cephalothin sodium, hydrocortisone sodium succinate, mitomycin, methotrexate, nafcillin sodium, aminophylline, ascorbic acid, terbutaline, divalent and trivalent cations (especially copper), compounds containing sulfhydryl groups, and precipitation by hydrophobic anions, essential amino acids, riboflavine, dexamethasone, and frusemide. 

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 anti-inflammatory potencies of betamethasone and dexamethasone exceed that of prednisolone. However, because of the facility with which prednisolone acetate crosses the cornea, a 1% solution is generally regarded as the drug of choice for the topical treatment of anterior uveitis in the horse, although comparable clinical results can be achieved using 0.1% dexamethasone in alcohol preparations. The frequency of application of topical glucocorticoids is largely determined by the severity and the nature of the clinical problem... 

There are three aerosolized corticosteroid preparatioias available in MDI formulation for administration to horses via the Equine AeroMask beclometasone dipropionate, fluticasone propionate and flunisolide (Table 16.2). In terms of the relative potency, fluticasone is more potent than beclometasone, which is more potent than flunisolide, which is equipotent to triamcinolone. Using dexamethasone as the standard (1.0), the relative glucocorticoid receptor affinity of the common corticosteroids is flunisolide 1.9, triamcinolone 2.0, beclometasone (active metabolite) 13.5 and fluticasone propionate 22.0 (Barnes et al 1998). The pulmonary residence time of the aerosolized corticosteroids is determined by the lipophilicity of each drug. Flunisolide has intermediate water solubility (lOmg/ml), simitar to... 

Depending on the location of ocular inflammation, a specific corticosteroid in a specific dosage form may be chosen. For instance, a corticosteroid of high potency, such as prednisolone acetate, fiuorometholone, or dexamethasone, may be chosen for deep-seated inflammation of the uveal tract. Further treatment of such inflammation may take the form of subtenon injections or oral (systemic) administration of selected corticosteroids, depending on the indication and the dosage forms available. For inflammation of a more superficial nature, the lower strengths of prednisolone acetate or the lower-potency corticosterioids, such as hydrocortisone or medrysone, will usually be chosen. 

Fluocinolone acetonide is a lipophilic, synthetic corticosteroid with a potency similar to dexamethasone. However, fluocinolone acetonide is 1 /24th as soluble as dexamethasone, which makes it very insoluble. Thus it can be released over a much longer period of time than dexamethasone without an excessively bulky polymer system (23 see also Chapter 14). A prospective, noncomparative interventional case... 

Dexamethasone has approximately 10 times the potency of cortisol. It is extremely long acting. 

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