actually its an assignment that included introduction, classification and pharmacology of corticosteroids.

1. Assignment of Applied Pharmacology
Topic: CORTICOSTEROIDS
Presented to: MAM AMBREEN
Presented by: ABDUL WAHEED QAISAR
Roll No. 10-PHL-S17
M. Phil Pharmacology
Faculty ofPharmacy
BahauddinZakariyaUniversity, Multan

2. Corticosteroids
Introduction:
The adrenal gland is the source of a diverse group of hormones essential for metabolic control,
regulation of water and electrolyte balance, and regulation of body’s response to stress.
Using cholesterol as a substrate, the adrenal cortex produces a large number of substances
collectively known as corticosteroids.
Classification of corticosteroids
There are some most commonly used natural and synthetic corticosteroids,
Short- to MEDIUM-ACTING GLUCOCORTICOIDS
Hydrocortisone (cortisol)
Cortisone
Prednisone
Prednisolone
Methylprednisolone
Meprednisone
Intermediate-acting glucocorticoids
Triamcinolone
Paramethasone
Fluprednisolone
Long-acting glucocorticoids
Betamethasone
Dexamethasone
Mineralocorticoids
Fludrocortisone
Desoxycorticosterone acetate
General Mechanism of Action:
Corticosteroids can be used as orally, parenteral, and inhalation and after passage through the
cell membrane corticosteroids reacts with receptor proteins in the cytoplasm to form a steroid-
receptor complex. This complex moves into the nucleus, where it binds to DNA. The binding
process then changes the transcription of messenger RNA (mRNA). Because mRNA acts as
template for protein synthesis, corticosteroids can either stimulate or inhibit the synthesis of
specific proteins.

3. Intracellular mechanismof actionof the glucocorticoidreceptor:
The figure shows the molecular pathway by which cortisol (labeled S) enters cells and interacts
with the glucocorticoid receptor (GR) to change GR conformation (indicated by the change in
shape of the GR), induce GR nuclear translocation, and activate transcription of target genes.
The example shown is one in which glucocorticoids activate expression of target genes; the
expression of certain genes, including pro-opiomelanocortin (POMC) expression by
corticotropes, is inhibited by glucocorticoid treatment.
CBG, corticosteroid binding globulin; GR, glucocorticoid receptor; S, steroid hormone; HSP90,
the 90-kd heat-shock protein; HSP70, the 70-kd heat- shock protein; IP, the 56-kd
immunophilin; GRE, glucocorticoid-response elements in the DNA that are bound by GR, thus
providing specificity to induction of gene transcription by glucocorticoids. Within the gene are
introns (unshaded) and exons (shaded); transcription and mRNA processing leads to splicing
and removal of introns and assembly of exons into mRNA.

4. CLINICAL PHARMACOLOGY
Adrenocortical insufficiency:
Chronic (Addison’s disease) — chronic adrenocortical insufficiency is characterized by
weakness, fatigue, weight loss, hypotension, hyperpigmentation, and inability to maintain the
blood glucose level during fasting. In such individuals, minor noxious, traumatic, or infectious
stimuli may produce acute adrenal insufficiency with circulatory shock and even death.
In primary adrenal insufficiency, about 20–30 mg of hydrocortisone must be given daily, with
increased amounts during periods of stress. Although hydrocortisone has some
mineralocorticoid activity, this must be supplemented by an appropriate amount of a salt-
retaining hormone such as fludrocortisone. Synthetic glucocorticoids that are long-acting and
devoid of salt-retaining activity should not be administered to these patients.
Acute— when acute adrenocortical insufficiency is suspected, treatment must be instituted
immediately. Therapy consists of large amounts of parenteral hydrocortisone in addition to
correction of fluid and electrolyte abnormalities and treatment of precipitating factors.
Hydrocortisone sodium succinate or phosphate in doses of 100 mg intravenously is given every
8 hours until the patient is stable. The dose is then gradually reduced, achieving maintenance
dosage within 5 days.
The administration of salt-retaining hormone is resumed when the total hydrocortisone dosage
has been reduced to 50 mg/d.
Cushing’s syndrome— Cushing’s syndrome is usually the result of bilateral adrenal hyperplasia
secondary to an ACTH-secreting pituitary adenoma (Cushing’s disease) but occasionally is due
to tumors or nodular hyperplasia of the adrenal gland or ectopic production of ACTH by other
tumors. The manifestations are those associated with the chronic presence of excessive
glucocorticoids.
When glucocorticoid hyper secretion is marked and prolonged, a rounded, plethoric face and
trunk obesity are striking in appearance.
The manifestations of protein loss are often found and include muscle wasting; thinning, purple
striae, and easy bruising of the skin; poor wound healing; and osteoporosis. Other serious
disturbances include mental disorders, hypertension, and diabetes. This disorder is treated by
surgical removal of the tumor producing ACTH or cortisol, irradiation of the pituitary tumor, or
resection of one or both adrenals. These patients must receive large doses of cortisol during
and after the surgical procedure. Doses of up to 300 mg of soluble Hydrocortisone may be
given as a continuous intravenous infusion on the day of surgery. The dose must be reduced
slowly to normal replacement levels, since rapid reduction in dose may produce withdrawal
symptoms, including fever and joint pain. If adrenalectomy has been performed, long-term
maintenance is similar to that outlined above for adrenal insufficiency.
Asthma:
Asthma is a common long-term inflammatory disease of the airways of the lungs. It is
characterized by variable and recurring symptoms, reversible airflow obstruction, and
bronchospasm. Symptoms include episodes of wheezing, coughing, chest tightness, and
shortness of breath.

5. Medications:
Medications used to treat asthma are divided into two general classes: quick-relief medications
used to treat acute symptoms and long-term control medications used to prevent further
exacerbation.
Fast-acting
Corticosteroids such as betamethasone, beclomethasone, dexamethasone etc. are used in
combination with short-acting beta2-adrenoceptor agonists such as salbutamol, in acute
asthma. In acute asthmatic conditions parenteral corticosteroids such as hydrocortisone also
recommended
Long–term control:
Corticosteroids are generally considered the most effective treatment available for long-term
control. Inhaled forms such as beclomethasone are usually used except in the case of severe
persistent disease, in which oral corticosteroids such as betamethasone, prednisolone may be
needed. Long-acting beta-adrenoceptor agonists and leukotriene receptor antagonists are used
in combination with corticosteroids for long term control of asthma.
Mode of Action:
Corticosteroids bind to cytosolic glucocorticoid receptors to decrease transcription and
production of inflammatory cytokines e.g. interleukin (IL)-4 (IL-4), IL-13, granulocyte
macrophage colony stimulating factor (GM-CSF), eotaxin and regulated on activation, normal T
cells expressed and secreted (RANTES), which function in bronchoconstriction and airway
inflammation.
Inflammatory Pain and Infection:
There are dozens of inflammatory disorders. Many occur when the immune systemmistakenly
triggers inflammation in the absence of infection, such as inflammation of the joints in
rheumatoid arthritis. Others result from a response to tissue injury or trauma but affect the
entire body. Inflammation or infection stimulate the cell through receptor by chemicals this
will activate nuclear factor kappa B with in the cell, nuclear factor kappa B activate within the
gene of the cell to produce mRNA and mRNA will be translated to inflammatory cytokines to
stimulate and promote the inflammatory response and this will make the sensitization of pain,
heat, redness etc. so this will promote inflammation to response. When glucocorticoids such as
Prednisolone, Triamcinolone, Dexamethasone are used, glucocorticoids are lipid soluble
hormones they travel around the body, when glucocorticoids enter the cell they bind with
glucocorticoid receptors and made complex then this complex inhibit the activity of nuclear
factor kappa B and made them inactive and thus it will not produce inflammatory cytokines or
inflammatory chemicals and so in this way they suppress the inflammation and this is why the
Glucocorticoid is a powerful anti-inflammatory drug.

6. IMMUNOSUPPRESSION
Immunosuppressive drugs are used to dampen the immune response in organ transplantation
and autoimmune disease. In transplantation, the major classes of immunosuppressive drugs
used today are: (1) glucocorticoids, (2) calcineurin inhibitors, (3) antiproliferative/antimetabolic
agents, and (4) biologics (antibodies). These drugs have met with a high degree of clinical
success in treating conditions such as acute immune rejection of organ transplants and severe
autoimmune diseases. However, such therapies require life- long use and nonspecifically
suppress the entire immune system, exposing patients to considerably higher risks of infection
and cancer.
Mechanism of action:
The immunosuppressive effects of glucocorticoids have long been known, but the specific
mechanism(s) of their immunosuppressive action remains somewhat elusive. Glucocorticoids
lyse (in some species) and induce the redistribution of lymphocytes, causing a rapid, transient
decrease in peripheral blood lymphocyte counts. To affect longer-term responses, steroids bind
to receptors inside cells; these receptors, glucocorticoid- induced proteins, or interacting
proteins regulate the transcription of numerous other genes. Additionally, glucocorticoid-
receptor complexes increase IκB expression, thereby curtailing activation of NF-κB, which
increases apoptosis of activated cells of central importance; key proinflammatory cytokines
such as IL-1 and IL-6 are down regulated. T cells are inhibited from making IL-2 and
proliferating. The activation of cytotoxic T lymphocytes is inhibited. Neutrophils and monocytes
display poor chemotaxis and decreased lysosomal enzyme release. Therefore, glucocorticoids
have broad anti-inflammatory effects on multiple components of cellular immunity. In contrast,
they have relatively little effect on humoral immunity.
Therapeutic uses of glucocorticoids:
There are numerous indications for glucocorticoids. They commonly are combined with other
immunosuppressive agents to prevent and treat transplant rejection. High dose pulses of
intravenous Methylprednisolone Sodium Succinate (SOLU-MEDROL) are used to reverse acute
transplant rejection and acute exacerbations of selected autoimmune disorders.
Glucocorticoids also are efficacious for treatment of graft-versus-host disease in bone-marrow
transplantation.
Rheumatic Disorders: Glucocorticoids are used widely in the treatment of a variety of
rheumatic disorders and are a mainstay in the treatment of the more serious inflammatory
rheumatic diseases, such as systemic lupus erythematosus, and a variety of vasculitic disorders,
such as polyarthritis nodosa, Wegener’s granulomatosis, Churg-Strauss syndrome, and giant cell
arteritis. For these more serious disorders, the starting dose of glucocorticoids should be
sufficient to suppress the disease rapidly and minimize resultant tissue damage. Initially,
Prednisone (1 mg/kg per day in divided doses) often is used, generally followed by
consolidation to a single daily dose, with subsequent tapering to a minimal effective dose as
determined by clinical variables.
While they are an important component of treatment of rheumatic diseases, glucocorticoids
are often used in conjunction with other immunosuppressive agents such as cyclophosphamide
and methotrexate, which offer better long-term control than steroids alone. In rheumatoid
arthritis, because of the serious and debilitating side effects associated with chronic use,

7. glucocorticoids are used as temporizing agents for progressive disease that fails to respond to
first-line treatments such as physiotherapy and nonsteroidal antinflammatory agents. In this
case, glucocorticoids provide relief until other, slower-acting anti-rheumatic drugs, such as
methotrexate or newer agents targeted at tumor necrosis factor take effect. A typical starting
dose is 5 to 10 mg of prednisone per day. In the setting of an acute exacerbation, higher doses
of glucocorticoids may be employed (typically 20 to 40 mg/day of prednisone or equivalent),
with rapid taper thereafter. Complete relief of symptoms is not sought, and the symptomatic
effect of small reductions in dose (decreases of perhaps 1 mg/day of prednisone every 2 to 3
weeks) should be tested frequently, while concurrent therapy with other measures is
continued, to maintain the lowest possible prednisone dose. Alternatively, patients with major
symptomatology confined to one or a few joints may be treated with intra-articular steroid
injections. Depending on joint size, typical doses are 5 to 20 mg of Triamcinolone Acetonide.
Skin Diseases:
Glucocorticoids are remarkably efficacious in the treatment of a wide variety of inflammatory
dermatoses. As a result, a large number of different preparations and concentrations of topical
glucocorticoids of varying potencies are available. A typical regimen for an eczematous eruption
is 1% Hydrocortisone ointment applied locally twice daily. Effectiveness is enhanced by
application of the topical steroid under an occlusive film, such as plastic wrap; unfortunately,
the risk of systemic absorption also is increased by occlusive dressings, and this can be a
significant problem when the more potent glucocorticoids are applied to inflamed skin.
Glucocorticoids are administered systemically for severe episodes of acute dermatologic
disorders and for exacerbations of chronic disorders. The dose in these settings is usually 40
mg/day of prednisone. Systemic steroid administration can be lifesaving in pemphigus, which
may require daily doses of up to 120 mg of prednisone.
Gastrointestinal Diseases:
Glucocorticoid therapy is indicated in selected patients with inflammatory bowel disease.
Patients who fail to respond to more conservative management (i.e., rest, diet, and
sulfasalazine) may benefit from glucocorticoids; steroids are most useful for acute
exacerbations. In mild ulcerative colitis, hydrocortisone (100 mg) can be administered as a
retention enema with beneficial effects. In more severe acute exacerbations, oral prednisone
(10 to 30 mg/day) frequently is employed. For severely ill patients—with fever, anorexia,
anemia, and impaired nutritional status larger doses should be used (40 to 60 mg prednisone
per day). Major complications of ulcerative colitis or Crohn’s disease may occur despite
glucocorticoid therapy, and glucocorticoids may mask signs and symptoms of complications
such as intestinal perforation and peritonitis.
Budesonide, a highly potent synthetic glucocorticoid that is inactivated by first pass hepatic
metabolism, reportedly has diminished systemic side effects commonly associated with
glucocorticoids. Oral administration of budesonide in delayed-release capsules (ENTOCORT, 9
mg/day) facilitates drug delivery to the ileum and ascending colon; the drug also has been used
as a retention enema in the treatment of ulcerative colitis.

8. General Precautions
Caution is necessary when oral corticosteroids are used in patients with the following
conditions and frequent monitoring is necessary:
• Hypertension
• Hypothyroidism
• Congestive Heart failure or recent myocardial infarction
• Liver failure
• Renal insufficiency
• Diabetes mellitus or in those with a family history of diabetes
• Osteoporosis
• Glaucoma
• Epilepsy and/or seizure disorder
• Peptic ulceration
• Previous steroid myopathy
• Tuberculosis
• Patients with myasthenia gravis receiving anticholinesterase therapy since
Prednisone may decrease plasma anticholinesterase activity
• Patients with thromboembolic disorders
• Patients with Cushing’s disease