Adverse Effects & Contraindications of Corticosteroids

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Chapter: Essential pharmacology : Corticosteroids

These are extension of the pharmacological action occurring with prolonged therapy, and are a great limitation to the use of corticoids in chronic diseases.


ADVERSE EFFECTS

 

These are extension of the pharmacological action occurring with prolonged therapy, and are a great limitation to the use of corticoids in chronic diseases.

 

A. Mineralocorticoid

 

Sodium and water retention, edema, hypokalaemic alkalosis and a progressive rise in BP. These are now rare due to availability of highly selective glucocorticoids.

 

Gradual rise in BP occurs due to excess glucocorticoid action as well.

 

B. Glucocorticoid

 

 

1.    Fragile skin, purple striae—typically on thighs and lower abdomen, easy bruising, telangiectasis, hirsutism. Cutaneous atrophy occurs with topical use also.

 

2.  Cushing’s habitus: characteristic appearance with rounded face, narrow mouth, supraclavicular hump, obesity of trunk with relatively thin limbs.

 

3.     Hyperglycaemia, may be glycosuria, precipitation of diabetes.

 

4. Muscular weakness: proximal (shoulder, arm, pelvis, thigh) myopathy occurs occasionally—withdraw corticoids.

 

5. Susceptibility to infection: this is nonspecific; latent tuberculosis may flare; opportunistic infections with low grade pathogens (Candida, etc.).

 

6.     Delayed healing: of wounds and surgical incisions.

 

7.  Peptic ulceration: risk is doubled; bleeding and silent perforation of ulcers may occur. Dyspeptic symptoms are frequent with high dose therapy.

 

8. Osteoporosis: Specially involving vertebrae and other flat spongy bones. Compression fractures of vertebrae and spontaneous fracture of long bones can occur, especially in the elderly. Radiological evidence of osteoporosis is an indication for withdrawal of corticoid therapy. Corticosteroid induced osteoporosis can be prevented/arrested by calcium supplements + vit D, bisphosphonates and by estrogen/androgen replacement therapy in females/males respectively.

 

a.      Avascular necrosis of head of femur, humerous, or knee joint is an occasional abrupt onset complication of high dose corticosteroid therapy.

 

9.     Posterior subcapsular cataract may develop after several years of use, especially in children.

 

10. Glaucoma: may develop in susceptible individuals after prolonged topical therapy.

 

11. Growth retardation: in children occurs even with small doses if given for long periods. Large doses do inhibit GH secretion, but this may in addition be a direct cellular effect of corticoids.

 

12. Foetal abnormalities: Cleft palate and other defects are produced in animals, but have not been encountered on clinical use in pregnant women. The risk of abortion, stillbirth or neonatal death is not increased, but intrauterine growth retardation can occur after prolonged therapy, and neurological/ behavioral disturbances in the offspring are feared. Prednisolone appears safter than dexa/beta methasone, because it is metabolized by placenta, reducing foetal exposure. Prolonged corticosteroid therapy during pregnancy increases the risk of gestational diabetes, pregnancy induced hypertension and preeclampsia.

 

13. Psychiatric disturbances: mild euphoria frequently accompanies high dose steroid treatment. This may rarely progress to manic psychosis. Nervousness, decreased sleep and mood changes are noted by few. Rarely a depressive illness occurs after longterm use.

 

14. Suppression of hypothalamo-pituitary-adrenal (HPA) axis: occurs depending both on dose and duration of therapy. In time, adrenal cortex atrophies and stoppage of exogenous steroid precipitates a withdrawal syndrome—malaise, fever, anorexia, nausea, postural hypotension, weakness, pain in muscles and joints and reactivation of the disease. Subjected to stress, these patients may go into acute adrenal insufficiency.

 

Any patient who has received > 20–25 mg/ day hydrocortisone or equivalent for longer than 2–3 weeks should be put on a scheme of gradual withdrawal: 20 mg hydrocortisone/ day reduction every week and then still smaller fractions once this level has been achieved. Such patients may need protection with steroids if a stressful situation develops up to one year after withdrawal. Administration of ACTH during withdrawal does not hasten recovery because it has been found that adrenals recover earlier than pituitary and hypothalamus.

 

If a patient on steroid therapy develops an infection—the steroid should not be discontinued despite its propensity to weaken host defence. Rather, the dose may have to be increased to meet the stress of infection.

 

Measures that minimise HPA axis suppression are:

 

a)  Use shorter acting steroids (hydrocortisone, prednisolone) at the lowest possible dose.

b)    Use steroids for the shortest period of time possible.

c)     Give the entire daily dose at one time in the morning.

d)    Switch to alternateday therapy if possible.

 

It has been found that moderate dose of a short acting steroid (e.g. prednisolone) given at 48 hr interval did not cause HPA suppression, whereas the same total amount given in 4 divided 12 hourly doses produced marked HPA suppression. Alternateday therapy also resulted in less immunological suppression—lower risk of infection. The longer acting steroids (dexamethasone, etc.) are not suitable for alternateday therapy. Only problem with alternateday therapy is that many steroid dependent patients are incapacitated on the ‘off day’.

 

e)  If appropriate, use local (dermal, inhaled, ocular, nasal, rectal, intrasynovial) preparations of a steroid with poor systemic availability (beclomethasone, triamcinolone acetonide, fluticasone, etc.)

 

CONTRAINDICATIONS

 

The following diseases are aggravated by corticosteroids. Since steroids may have to be used as a lifesaving measure, all of these are relative contraindications:

 

Peptic ulcer

 

Diabetes mellitus

 

Hypertension

 

Viral and fungal infections

 

Tuberculosis and other infections

 

Osteoporosis

 

Herpes simplex keratitis

 

Psychosis

 

Epilepsy

 

CHF

 

Renal failure

 

Combination of any drug with corticosteroids in fixed dose formulation for internal use is banned.

 

Metyrapone

 

Inhibits 11β hydroxylase in adrenal cortex and prevents synthesis of hydrocortisone increased ACTH release increased excretion of 11desoxycortisol in urine. Thus, it is used to test the responsiveness of pituitary and its ACTH producing capacity.

 

Aminoglutethimide, trilostane and high doses of the antifungal drug Ketoconazole also inhibit steroidogenic enzymes—occasionally used to treat Cushing’s disease. Ketoconazole reduces gonadal steroid synthesis as well.

 

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