adrenal corticosteroids, antagonists, corticotropin plasma proteins. Some details of preparations and equivalent doses are given in the table. Injectable and topical forms are available (creams, suppositories, eye drops).
The selectivity of hydrocortisone for the glucocorticoid receptor is not due to a different binding affinity of hydrocortisone to the two receptors but to the protection of the mineralocorticoid receptor by locally high concentrations of the enzyme 11 ß-hydroxysteroid dehydrogenase, which converts Cortisol (hydrocortisone) to the inactive cortisone. This enzyme is inhibited by one of the components of liquorice, and can occasionally harbour a genetic defect. Therefore both acquired (in liquorice addicts) and inherited syndromes of 'pseudohyperaldo-steronism' can occasionally occur.
Hydrocortisone (Cortisol) is the principal naturally occurring steroid; it is taken orally; a soluble salt can be given i.v. for rapid effect in emergency (whether due to deficiency, allergy or inflammatory disease). A suspension (Hydrocortisone Acetate Inj.) can be given intra-articularly.
Parenteral preparation for systemic effect: the soluble Hydrocortisone Sodium Succinate Inj. is used for quick (1-2 h) effect; for continuous effect about 8-hourly administration is appropriate. Prednisolone Acetate Inj. i.m. is an alternative, once or twice a week.
Oral tablet strengths, see Table 34.1.
Prednisolone is predominantly anti-inflammatory (glucorticoid), biologically active, and has little sodium-retaining activity; it is the standard choice for anti-inflammatory pharmacotherapy, orally or i.m.
Prednisone is a prodrug, i.e. it is biologically inert and converted into prednisolone in the liver. Since there is 20% less on conversion there seems to be no point in using it.
Methylprednisolone is similar to prednisone; it is used i.v. for megadose pulse therapy (see below).
Fluorinated corticosteroids: triamcinolone has virtually no sodium retaining (mineralocorticoid) effect but has the disadvantage that muscle wasting may occasionally be severe and anorexia and mental depression may be more common at high dose.
Dexamethasone and betamethasone are similar, powerful predominantly anti-inflammatory steroids. They are longer-acting than prednisolone and are used for therapeutic adrenocortical suppression.
Fludrocortisone has a very great sodium-retaining effect in relation to its anti-inflammatory action, and only at high doses need the nonelectrolyte effects be considered. It is used to replace aldosterone where the adrenal cortex is destroyed (Addison's disease). Fludrocortisone is also the drug of choice in most patients with autonomic neuropathy, in whom volume expansion is easier to achieve than a sustained increase in vasoconstrictor tone. Much higher doses of fludrocortisone (0.5-1.0 mg) are required when the cause of hypotension is a salt-losing syndrome of renal origin, e.g. following an episode of interstitial nephritis.
Aldosterone (t'/2 20 min), the principal natural salt-retaining hormone, has been used i.m. in acute adrenal insufficiency. After oral administration, it is rapidly inactivated in the first pass through the liver but has no place in routine therapeutics, as fludrocortisone is as effective and is active orally.
Spironolactone (see p. 534) is a competitive aldosterone antagonist which also blocks the mineralocorticoid effect of other steroids; it is used in the treatment of primary hyperaldosteronism and as a diuretic, principally when severe oedema is due to secondary hyperaldosteronism, e.g. cirrhosis, congestive cardiac failure.
Beclomethasone and budesonide are used by inhalation for asthma (see p. 561). About 90% of an inhalation dose is swallowed and these steroids are inactivated by hepatic first-pass; the rest, absorbed from the mouth and lungs, gives very low systemic plasma concentration. The risk of suppression of the hypothalamic/pituitary/adrenal axis is thus minimal (but it can happen). This property of extensive hepatic first-pass metabolism with low systemic availability is also an advantage in the topical treatment of inflammatory bowel disease with minimal risk of systemic adverse effects.
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