CORTICOSTEROID

Classification

Figure 1 - Based on duration of action

Figure 2Based on
chemical
structure.
Allergic
reactions to
one member
of a class
typically
indicate an
intolerance
of all
members of
the class.
This is
known as
the

"Coopman classification",[22] after S. Coopman, who defined this classification in

1989

Advantages
Corticosteroids can be life-saving and have dramatic benefits. However, their
therapeutic use has to be balanced against the risks of serious adverse effects.

Dose, route of administration, duration of treatment and choice of corticosteroid must

be considered to maximise therapeutic benefit and minimise adverse effects.

Disadvantages
Adverse effects are dose-related and often predictable according to the glucocorticoid
actions (eg, diabetes, osteoporosis, muscle wasting, neuropsychiatric effects) and
mineralocorticoid actions (eg, hypertension, and electrolyte and fluid balance).
There is a wide range of adverse effects:

Cardiovascular: hypertension; congestive cardiac failure.

Central nervous system: mood disturbance (including mania), psychosis, sleep

disturbance

Endocrine/metabolic: adrenal suppression, growth failure in children, insulin

resistance, diabetes, disturbance of thyroid function, hypokalaemia, metabolic alkalosis.

Gastrointestinal: gastric effects (peptic ulceration, etc), fatty liver.

Haematopoietic: leukocytosis and other effects (eg, reduced eosinophils and

monocytes).

Immune system:

Suppression type IV hypersensitivity (interferes with Mantoux test).

Inhibitory effects (leukocytes, macrophages, cytokines).

Suppression of primary antigen response (important with vaccines).

Musculoskeletal system:

Myopathy (especially proximal muscles).

Osteoporosis.

Avascular necrosis of bone.

Ophthalmic: cataracts (more common in children), elevation of intraocular pressure,

glaucoma.

Skin and other systems: moon face, truncal obesity, dorsolumbar hump, acne, thin
skin, skin striae (violaceous), impotence, irregular periods.

Dosage
Glucocorticoid-Responsive Conditions
5-60 mg/day PO in single daily dose or divided q6-12hr
Dosing considerations

When converting from immediate-release to delayed-release formulation, note that

delayed-release formulation takes about 4 hours to release active substances
Note that exogenous steroids suppress adrenal cortex activity least during maximal
natural adrenal cortex activity (between 4:00 and 8:00 AM)
Administration
Take with meal or snack
High-dose glucocorticoids may cause insomnia; immediate-release formulation is typically
administered in morning to coincide with circadian rhythm
Delayed-release formulation takes about 4 hours to release active substances; thus, with
this formulation, timing of dose should take into account delayed-release pharmacokinetics

and disease or condition being treated (eg, may be taken at bedtime to decrease morning
stiffness with rheumatoid arthritis)

Treatment Cushings Syndrome

Basically, the treatment depends on the etiology. The aim of treatment of Cushing's
syndrome is to remove or destroy the basic lesion and thus correct hypersecretion of adrenal
hormones without inducing pituitary or adrenal damage, which requires permanent
replacement therapy for hormone deficiencies.
Medications used in the management of Cushing syndrome include the following:

Somatostatin analogs:

Pasireotide: binds and activates human somatostatin receptors resulting in

inhibition of ACTH secretion, which leads to decreased cortisol secretion. It is
indicated for treatment of adults with Cushing disease in whom pituitary
surgery is not an option or has not been curative.
Adrenal steroid inhibitors:
Metyrapone: competitively inhibits a single steroidogenic enzyme, 11-betahydroxylase, activity, the final step in cortisol synthesis. Therapy is begun at 1
g/d divided into 4 doses and increased to a maximum dose of 4.5 g/d. Adverse
effects present from increases in androgen and mineralocorticoid precursors
and include hypertension, acne, and hirsutism.
Ketoconazole: acts on several of the P450 enzymes, including the first step
in cortisol synthesis, cholesterol side-chain cleavage, and conversion of 11deoxycortisol to cortisol. A daily dose of 600-800 mg often decreases cortisol
production.
Etomidate: an imidazole-derivative anesthetic agent, blocks 11-betahydroxylase. It is used intravenously at 0.3 mg/kg/h. Its use is limited by the
requirement for administration by the intravenous route. However, it rapidly
decreases cortisol concentration and may be used as an adjunct to impending
surgical procedure.
Glucocorticoid receptor antagonist:
Mifepristone: antiprogestational agent, which, at high doses, competitively
binds to the glucocorticoid and progesterone receptors.
Adrenolytic agents:
Mitotane: an adrenolytic agent that acts by inhibiting 11-beta hydroxylase
and cholesterol side-chain cleavage enzymes. This drug also leads to
mitochondrial destruction and necrosis of adrenocortical cells in the zona
fasciculata and reticularis. For this reason, it is used in treatment of adrenal
cancer at doses of 2-4 g daily. Its survival benefit is unclear.