Pharmacotherapy

Suppression of adrenocortical function

In adrenogenital syndrome and adrenal virilism, an attempt may be made to suppress excess adrenal androgen secretion by inhibiting pituitary corticotropin production by means of prednisolone or dexamethasone. Suppression of androgen production is effective if there is adrenal hyperplasia, but not if an adrenal tumour is present. Hairiness, which women especially dislike in themselves, is often unaffected even though good suppression is achieved, and menstruation recommences.

Use in inflammation and for immunosuppression

Only a brief survey can be given here.

Drugs with primarily glucocorticoid effects, e.g. prednisolone, are chosen, so that dosage is not limited by the mineralocorticoid effects that are inevitable with hydrocortisone. But it remains essential to use only the minimum dose that will achieve the desired effect. Sometimes therapeutic effect must be partly sacrificed to avoid adverse effects, for it has not yet proved possible to separate the glucocorticoid effects from each other; indeed it is not known if it is possible to eliminate catabolic effects and at the same time retain anti-inflammatory action. In any case, in some conditions, e.g. nephrotic syndrome, the clinician cannot specify exactly what action they want the drug developer to provide.

Further specific uses

The decision to give a corticosteroid commonly depends on knowledge of the likelihood and amount of benefit (bearing in mind that very prolonged high dose inevitably brings serious complications such as osteoporosis), on the severity of the disease and on whether the patient has failed to respond usefully to other treatment. It often requires expertise that can be imparted only by those with wide experience of the disease concerned. The following are examples.

Adrenal steroids are used in all or nearly all cases of:

• Exfoliative dermatitis and pemphigus, if severe

• Collagen diseases, if severe, e.g. lupus erythematosus (systemic), polyarteritis nodosa, polymyalgia rheumatica and cranial giant cell arteritis (urgent therapy to save sight), dermatomyositis

• Acute severe asthma

• Acute lymphatic leukaemia (see p. 617)

• Acquired haemolytic anaemia

• Severe allergic reactions of all kinds, e.g. serum sickness, angio-oedema, trichiniasis. Alone they will not control acute manifestations of anaphylactic shock as they do not act quickly enough

• Organ transplant rejection

• Acute spinal cord injury: early, brief, and high dose (to reduce the oedema/inflammation)

• Autoimmune active chronic hepatitis: a corticosteroid improves wellbeing, liver function and histology; prednisolone will benefit some 80% and should be continued in the long term, as most patients relapse if the drug is withdrawn.

Adrenal steroids are used in some cases of:

• Rheumatic fever

Rheumatoid arthritis

Ankylosing spondylitis

• Ulcerative colitis and proctitis

Regional enteritis (Crohn's disease)

Bronchial asthma and hay-fever (allergic rhinitis): also some bronchitics with marked airways obstruction.

• Sarcoidosis. If there is hypercalcaemia or threat to a major organ, e.g. eye, adrenal steroid administration is urgent. Pulmonary fibrosis may be delayed and central nervous system manifestations may improve.

• Acute mountain/altitude sickness, to reduce cerebral oedema.

• Prevention of adverse reaction to radiocontrast media in patients who have had a previous severe reaction.

• Blood diseases due to circulating antibodies, e.g. thrombocytopenic purpura (there may also be a decrease in capillary fragility with lessening of purpura even though thrombocytes remain few); agranulocytosis.

Eye diseases. Allergic diseases and nongranulomatous inflammation of the uveal tract. But bacterial and virus infections may be made worse and use of steroids to suppress inflammation of infection is generally undesirable, is best left to ophthalmologists and must be accompanied by effective chemotherapy; this is of the greatest importance in herpes virus infection. Corneal integrity should be checked before use (by instilling a drop of fluorescein). Prolonged use of corticosteroid eye drops causes glaucoma in 1 in 20 of the population (a genetic trait). Application is generally as hydrocortisone, prednisolone or fluorometholone drops, or subconjunctival injection.

• Nephrotic syndrome. Patients with minimal change disease respond well to daily or alternate day therapy. With a total of prednisolone 60 mg/ d, 90% of those who will lose their proteinuria will have done so within 4-6 weeks, and the dose is tapered off over 3-4 months. Longer courses only induce adverse effects. Relapses are common (50%) and it is then necessary to find a minimum dose of steroid that will keep the patient well. If a steroid is for any reason undesirable, cyclophosphamide or chlorambucil may be substituted. Membranous nephropathy may respond to high dose corticosteroid with or without chlorambucil.

• A variety of skin diseases, such as eczema. Severe cases may be treated by occlusive dressings if a systemic effect is not wanted, though absorption can be substantial (see Ch. 16).

• Acute gout resistant to other drugs (see p. 297).

• Hypercalcaemia of sarcoidosis and of vitamin D intoxication responds to prednisolone 30 mg daily (or its equivalent of other steroid) for

10 days. Hypercalcaemia of myeloma and some other malignancies responds more variably. Hyperparathyroid hypercalcaemia does not respond.

• Raised intracranial pressure due to cerebral oedema, e.g. in cerebral tumour or encephalitis (probably an anti-inflammatory effect which reduces vascular permeability and acts in 12-24 h): give dexamethasone 10 mg i.m. or i.v. (or equivalent) initially and then 4 mg 6-hourly by the appropriate route, reducing dose after 2-4 days and withdrawing over 5-7 days; but much higher doses may be used in palliation of inoperable cerebral tumour.

• Preterm labour: (to mother) to enhance fetal lung maturation.

• Aspiration of gastric acid (Mendelsohn's syndrome).

Myasthenia gravis: see page 439.

Use in diagnosis: dexamethasone suppression test. Dexamethasone acts on the hypothalamus (like hydrocortisone), to reduce output of corticotropin releasing hormone (CRH), but it does not interfere with measurement of corticosteroids in blood or urine. Normal suppression of Cortisol production after administering dexamethasone indicates that the hypothalamic/pituitary/adrenal axis is intact. Failure of suppression implies pathological hypersecretion of ACTH by the pituitary or of Cortisol by the adrenal. Dexamethasone is used because its action is prolonged (24 h). There are several ways of carrying out the test.

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