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.
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.
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.)
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.
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.
Related Topics
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