Hydrocortisone, effect

Since the introduction of cortisone (1) (1948) and hydrocortisone (2) (1951), adrenal-cortical hormones have remained an important and unreplaced dmg class. Though not without adverse effects, these compounds have continued to be the dmg of choice in the treatment of afflictions ranging from the moderate skin rash to severe acute inflammatory disorders, and are included in many other therapeutic regimes. 

Hydrocortisone and Prednisolone. Following the discovery of the antiinflammatory actions of cortisone (1) and cortisol (2), there was a need not only to develop highly efficient routes to the corticoids, but to discover novel stmctures with fewer side effects than those of the corticoids, eg, sodium and water retention, reduced carbohydrate tolerance (steroid diabetes), osteoporosis, and depressed host defense. 

When in the late 1940 s the remarkable therapeutic effects of the glucocorticoids cortisone and hydrocortisone were discovered, new raw materials had to be developed to produce these complicated molecules, and new synthetic methods devised to convert either a 20-ketopregnane or 21-acetoxy-20-ketopregnane to the dihydroxyacetone side-chain characteristic of these corticoids. This latter challenge produced some extremely useful new organic chemical reactions, many of which have wider application outside of steroids. 

Hydrocortisone, desonide—corticosteroids for anti-inflammatoiy and antipruritic effects... 

Janah S, Hussain QZ, Chaudhuri SN. 1970. Effect of hydrocortisone on immune cytokinetics. Part 1-Effects of different dose schedules on 19S and 7S antibody forming cells in Jeme s plaque technique. Indian J Med Res 58 1206-1216. 

Figure 4. Effect of pretreatment with hydrocortisone (50 mg/kg) on response of animal to a lethal injection of palytoxin (0.01 /ig/kg).

Monitor for adverse reactions from hydrocortisone administration. Glucocorticoid therapy at physiologic replacement doses should not lead to the development of Cushing s syndrome. However, careful monitoring should still be performed. Use the smallest effective dose. 

Corticosteroids (hydrocortisone, COCs may inhibit metabolism of corticosteroids Increase side effects of corticosteroids... 

Amphotericin B is the mainstay of treatment of patients with severe endemic fungal infections. The conventional deoxycholate formulation of the drug can be associated with substantial infusion-related adverse effects (e.g., chills, fever, nausea, rigors, and in rare cases hypotension, flushing, respiratory difficulty, and arrhythmias). Pre-medication with low doses of hydrocortisone, acetaminophen, nonsteroidal anti-inflammatory agents, and meperidine is common to reduce acute infusion-related reactions. Venous irritation associated with the drug can also lead to thrombophlebitis, hence central venous catheters are the preferred route of administration in patients receiving more than a week of therapy. 

Adrenocorticoid suppression may occur, so replacement therapy with hydrocortisone may be required. Other side effects include rash (which usually resolves in 5-8 days), lethargy, and anorexia. 

Armed with the above insight, we can examine the pharmacological ramifications of esterifying hydrocortisone. In Fig. 5 the ability of hydrocortisone esters to suppress inflammation induced by tetra-hydrofurfural alcohol, which acts simultaneously as irritant and vehicle, is shown as a function of the alkyl chain length of the esters [56]. An optimum chain in effect is seen at an alkyl chain length of six (hexanoate),... 

The slow and linear fluxes of hydrocortisone and dexamethasone under various hydrodynamic conditions are quantified in terms of effective permeability coefficients, P by Eq. (9), i.e.,... 

The summary of Pe values for the steroids as a function of stirring rates is found in Table 11 and their correlations with log PC (n-octanol-water) in Figure 20. The transport kinetics of the relatively hydrophilic hydrocortisone and dexa-methasone are controlled by passive diffusion across the cell monolayer. On the other hand, the Pe values of testosterone and progesterone are highly dependent on stirring rate. The results for testosterone are used to obtain the relationships between the effective permeability coefficients of the ABL on the donor and receiver sides and the stirring rate, using the linear expression (see Eq. (69)]... 

Other potential adverse effects include impaired absorption of fat-soluble vitamins A, D, E, and K hypernatremia and hyperchloremia GI obstruction and reduced bioavailability of acidic drugs such as warfarin, nicotinic acid, thyroxine, acetaminophen, hydrocortisone, hydrochlorothiazide, loperamide, and possibly iron. Drug interactions may be avoided by alternating administration times with an interval of 6 hours or greater between the BAR and other drugs. 

Low-potency products (e.g., hydrocortisone 1%) have a weak antiinflammatory effect and are safest for long-term application, for use on the face and intertriginous areas, for use with occlusion, and for use in infants and young children. 

Hydrocortisone, cortisone, and prednisone are the glucocorticoids of choice, administered twice daily at the lowest effective dose while mimicking the normal diurnal rhythm of cortisol production. 

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