Dosage And Routes Of Administration

Dosage depends very much on the purpose for which the steroid is being used and on individual response. There is no single schedule that will suit every case but examples appear below.

Systemic commencing doses

• For a serious disease such as systemic lupus, dermatomyositis: prednisolone up to 0.75-2.0 mg/kg/d orally in divided doses.

• If life-threatening, prednisolone up to 70 mg, or its equivalent of another steroid. The dose is then increased if necessary until the disease is controlled or adverse effects occur; as much as prednisolone 2-3 mg/kg/d can be needed. Cyclophosphamide or azathioprine (see p. 292) are valuable adjuncts; they may enhance the initial control of the disease and have a sparing effect on the maintenance dose of prednisolone required.

• More usually now, megadose pulses (methylprednisolone 1.0 g i.v. daily for 3 days) are used, followed by oral maintenance with prednisolone and/or a steroid-sparing agent (above).

• For less dangerous disease, such as rheumatoid arthritis: prednisolone 7.5-10.0 mg daily, adjusted later according to the response.

• In some special cases, including replacement of adrenal insufficiency, dosage is given in the account of the treatment of the disease.

• For continuous therapy the minimum amount to produce the desired effect must be used. Sometimes imperfect control must be accepted by the patient because full control, e.g. of rheumatoid arthritis, though obtainable, involves use of doses that must lead to long-term toxicity, e.g. osteoporosis, if continued for years. The decision to embark on such therapy is a serious matter for the patient.

Topical applications (creams, intranasal, inhalations, enemas) are used in attempts, often successful, to obtain local, whilst avoiding systemic, effects; suspensions of solutions are also injected into joints, soft tissues and subconjunctivally. All these can, with heavy dose, be sufficiently absorbed to suppress the hypothalamus and cause other unwanted effects. Individual preparations are mentioned in the text where appropriate.

The relatively high selectivity of inhaled bec-lomethasone in asthma is due to a combination of route of administration, high potency and rapid conversion to inactive metabolites by the liver of any drug that is absorbed (see asthma, skin); but yet hypothalamic/pituitary suppression and systemic toxicity occasionally occur.

Contraindications to the use of adrenal steroids for suppressing inflammation are all relative, depending on the advantage to be expected. They should be used only for serious reasons if the patient has: diabetes, a history of mental disorder or peptic ulcer, epilepsy, tuberculosis, hypertension or heart failure. The presence of any infection demands that effective chemotherapy be begun before the steroid, but there are exceptions (some viral infections, see above). Topical corticosteroid applied to an inflamed eye (with the very best of intention) can be disastrous if the inflammation is due to herpes virus.

Steroids containing fluorine (see above) intensify diabetes more than others and so should be avoided in that disease.

Long-term use of adrenal steroids in children presents essentially the same problems as in adults except that growth is retarded approximately in proportion to the dose. This is unlikely to be important unless therapy exceeds 6 months; there is a spurt of growth after withdrawal. Intermittent dosage schedules (alternate day) may reduce the risk (rarely, corticotropin may be preferred, see p. 675).

Some other problems loom larger in children than in adults. Common childhood viral infections may be more severe, and if a nonimmune child taking an adrenal steroid is exposed to one, it is wise to try to prevent the disease with the appropriate specific immunoglobulin (if available).

Live virus vaccination is unsafe in immuno-suppressed subjects, e.g. systemic prednisolone > 2 mg/kg per day for > 1 week in the preceding 3 months, as it may cause the disease, but active immunisation with killed vaccines or toxoids will give normal response unless the dose of steroid is high, when the response may be suppressed.

Raised intracranial pressure may occur more readily in children than in adults.

Fixed-dose combinations of adrenal steroids with other drugs in one tablet should never be used as they abrogate the principles for the use of such formulations (p. 118).

• Replacement of hormone deficiency

• Inflammation suppression

• Immunosuppression

• Suppression of excess hormone secretion

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