• Corticosteroids are a class of steroid hormones that are produced in the
• Corticosteroids are involved in a wide range of physiologic systems such as
immune response and regulation of inflammation,
blood electrolyte levels, and
3. • Using cholesterol as a substrate, the adrenal cortex produces a large number
of substances collectively known as corticosteroids
• At least two of these groups –
4. Glucocorticoids such as cortisol control carbohydrate, fat and protein
metabolism and are anti-inflammatory by preventing phospholipid release,
decreasing eosinophil action and a number of other mechanisms.
Rate of secretion of the principal steroids - 10-20 mg daily
Mineralocorticoids such as aldosterone control electrolyte and water
levels, mainly by promoting sodium retention in the kidney.
Rate of secretion of the principal steroids - 0.125 mg daily
1855 – Addison`s disease
1856 – Adrenal glands essential for life
1930 – Cortex > medulla
1932 – Cushing’s syndrome
1952 – Aldosterone
8. Classification of steroids based on their relative activity:
(t1/2 < 12 hr)
• Methyl prednisole
(t1/2 12 – 36)
(t1/2 > 36 hrs) 8
9. Classification of steroids based on their relative activity:
• Deoxycorticosterone acetate(DOCA)
10. Routes of adm: of corticosteroids
1. Topical steroid for use topically on the skin, eye, and mucous membranes.
2. Inhaled steroids for use to treat the nasal mucosa, sinuses, bronchi, and
3. Oral forms - such as prednisone and prednisolone.
4. Systemic forms - available in injectables for use intravenously and parenteral
11. FATE OF CORTICOSTEROIDS
75% - excreted in urine
25% - excreted in bile and feces
Conjugated to form glucuronides and to a lesser extent form
Degraded mainly in liver
12. Mechanism of action of Glucocorticoids
• Transactivation - Glucocorticoids bind to the cytosolic glucocorticoid receptor (GR), a type
of nuclear receptor that is activated by ligand binding. After a hormone binds to the corresponding
receptor, the newly formed complex translocate itself into the cell nucleus, where it binds
to glucocorticoid response elements (GRE) in the promoter region of the target genes resulting in
the regulation of gene expression.
• Trans repression - Transcription is repressed, but the activated GR is not interacting with DNA,
but rather with another transcription factor directly, thus interfering with it, or with other proteins that
interfere with the function of other transcription factors. This latter mechanism appears to be the most
likely way that activated GR interferes with NF-κB - namely by recruiting histone deacetylase, which
deacetylate the DNA in the promoter region leading to closing of the chromatin structure where NF-
κB needs to bind.
• Nongenomic effects - Activated GR has effects that have been experimentally shown to be
independent of any effects on transcription and can only be due to direct binding of activated GR with
other proteins or with mRNA.
16. Mechanism of action of Mineralocorticoids
• Genomic mechanisms
Mineralocorticoids bind to the mineralocorticoid receptor in the cell cytosol, and are able to
freely cross the lipid bilayer of the cell. This type of receptor becomes activated
upon ligand binding. After a hormone binds to the corresponding receptor, the newly
formed receptor-ligand complex translocate into the cell nucleus, where it binds to
many hormone response elements (HREs) in the promoter region of the target genes in
The opposite mechanism is called trans repression. The hormone receptor without ligand
binding interacts with heat shock proteins and prevents the transcription of targeted genes.
1. Hydrocortisone (cortisol) Acts rapidly but has short duration of action. In
addition to primary glucocorticoid, it has significant mineralocorticoid activity as
well. Used for:
Shock, status asthmaticus, acute adrenal insufficiency
Topically and as suspension for enema in ulcerative colitis
2. Prednisolone It is 4 times more potent than hydrocortisone, also more selective
glucocorticoid, but fluid retention does occur with high doses. Has intermediate
duration of action: causes less pituitary-adrenal suppression when a single
morning dose or alternate day treatment is given. Used for
autoimmune diseases and in malignancies
3. Methylprednisolone Slightly more potent and more selective than
prednisolone: 4–32 mg/ day oral. Methylprednisolone acetate has been used
as a retention enema in ulcerative colitis.
Pulse therapy with high dose methylprednisolone (1 g infused i.v. every 6–8
weeks) has been tried in nonresponsive active rheumatoid arthritis, renal
transplant, pemphigus, etc. with good results and minimal suppression of
pituitary adrenal axis.
4. Triamcinolone Slightly more potent than prednisolone but highly selective
glucocorticoid: 4–32 mg/day oral, 5–40 mg i.m., intraarticular injection. Also
5. Dexamethasone Very potent and highly selective glucocorticoid. It is also
long-acting, causes marked pituitary-adrenal suppression, but fluid retention
and hypertension are not a problem.
It is used for inflammatory and allergic conditions
6. Betamethasone Similar to dexamethasone
7. Desoxycorticosterone acetate (DOCA) It has only mineralocorticoid activity.
Used occasionally for replacement therapy in Addison’s disease
8. Fludrocortisone A potent mineralocorticoid having some glucocorticoid
activity as well, orally active, used for:
Replacement therapy in Addison’s disease
Congenital adrenal hyperplasia in patients with salt wasting
Idiopathic postural hypotension
9. Aldosterone It is the most potent mineralocorticoid. Not used clinically because
of low oral bioavailability and difficulties in regulating doses.
22. Deficiency of corticosteroids
There are three major types of adrenal insufficiency.
• Primary adrenal insufficiency is due to impairment of the adrenal glands.
• 80% are due to an autoimmune disease called Addison's disease or autoimmune adrenalitis.
• One subtype is called idiopathic
• Other cases are due to congenital adrenal hyperplasia or an adenoma (tumor) of the adrenal gland.
• Secondary adrenal insufficiency is caused by impairment of the pituitary gland or hypothalamus. Its
principal causes include pituitary adenoma (which can suppress production of adrenocorticotropic
hormone (ACTH) and lead to adrenal deficiency unless the endogenous hormones are replaced);
and Sheehan's syndrome, which is associated with impairment of only the pituitary gland.
• Tertiary adrenal insufficiency is due to hypothalamic disease and a decrease in the release
of corticotropin releasing hormone (CRH). Causes can include brain tumors and sudden withdrawal
from long-term exogenous steroid use (which is the most common cause overall).