Corticosteroids

Corticosteroids
• Hormones produced by the

adrenal cortex.
• Glucocorticoids, mineralocorticoids and a
small amount of androgens.
• Cortisol is the major glucocorticoid while
aldosterone is the major mineralocorticoid.
Part of adrenal gland Hormone secreted
Cortex[outer]
• Zona glomerulosa Aldosterone
• Zona fasciculate Cortisol
• Zona reticilaris Androgens
Medulla[inner] Adrenaline and NA

Basal secretions
Group Hormone Daily
secretions
Glucocorticoids • Cortisol 5 – 30 mg
• Corticosterone 2 – 5 mg
Mineralocorticoid • Aldosterone 5 – 150 μg
s • 11- deoxycorticosterone Trace
Sex Hormones
•Androgen • DHEA 15 – 30 mg
•Progestogen • Progesterone 0.4 – 0.8 mg
•Oestrogen • Oestradiol Trace
Cholesterol ACTH
Oestriol
Pregnenolone 17-α- Hydroxy Dehydro-epi
pregnenolone androsterone
Progesterone 17- Hydroxy Andro-

Oestrone
progesterone stenedione
11-Desoxy- 21,β hydroxylase

corticosterone
11- Desoxy-
cortisol
Corticosterone
11,β hydroxylase
18-Hydroxy-
corticosterone
ALDOSTERONE CORTISOL TESTOSTERONE OESTRADIOL

Mechanism of action of steroid hormones
• Corticosteroids enters the cell as free molecules

and binds to cytosolic steroid receptor; the
complex translocates to the nucleus and the
steroid binds to the glucocorticoid responsive
element[GRE] in the regulatory region of the
concerned gene. This leads to transcription of
mRNA which is exported to the cytoplasm. In the
cytoplasm, the mRNA causes translation of
proteins and bring about the final response.
Pharmacological actions
• Metabolic effects:
– Carbohydrate metabolism –
• ↓ peripheral utilization of glucose
• Stim. Glucose synthesis from amino acids
by ↓ protein synthesis[gluconeogenesis]
• Promote glycogen deposition in liver
– Protein metabolism –
• Catabolism
• Negative nitrogen balance
− Fat metabolism
• Lipolysis → Redistribution of fat
• ↑ FFA
• Buffalo hump
• Moon face
− Calcium metabolism
• ↓Intestinal absorption
• ↑ Renal excretion
• Excessive loss of calcium from spongy bones
(e.g., vertebrae, ribs, etc)
Electrolyte and water balance
• Aldosterone is more important
• Act on DT and CD of kidney
– Na+ reabsorption
– Urinary excretion of K+ and H+
Anti-inflammatory action:
 Decreases neutrophils, lymphocytes, eosinophils,

basophils and monocytes
 Suppressed all the components and stages of
inflammation
 Biochemical mechanism for cellular effects
• Inhibitors of phospholipase A2
• Decrease cyclooxygenase pathway
• Decrease IL2
• Decrease platelets activating factor[PAF]
• Decrease inflammatory cytokines
Corticosteroids
Lipocortin
Phospholipids
Phospholipase A2
Arachidonic acids
lipoxygenase Cycylooxygenase
Prostaglandins,
Leukotriene Thromboxane
PAF by lipocortin Prostacyclins
Immunosuppresive effects
• Inhibits cell mediated immunological
function in which T cells are primarily
involved
• Factors involved may be inhibition of IL-1
release from macrophages; inhibition of
IL-2 formation and action- T cell
proliferation is not stimulated. Suppression
of natural killer cells etc
Cardiovascular system
• Restrict capillary permeability, maintain
tone of arterioles and myocardial
contractility
• Potentiate the response of vascular
smooth muscles to the pressor effects of
catecholamines and angiotensin ll.
Skeletal Muscles
• Needed for maintaining the normal function
of Skeletal muscle
Addison's disease: weakness and fatigue is
due to inadequacy of circulatory
system
Prolonged use: muscle wasting and

myopathy
CNS
• Mild euphoria with pharmacological doses
• Increased motor activity, insomnia,
hypomania or depression
• Patients with Addison’s disease suffer from
apathy, depression and occasionally
psychosis
• High doses lower seizure threshold
Stomach
Aggravate peptic ulcer. May be due to:
– increased acid and pepsin secretion
– decreased immune response to

H.Pylori
Blood
 increase the number of RBCs, platelets
and neutrophils in circulation
 Decrease the lymphocytes, eosinophils
and basophils
Respiratory system
• Not bronchodilators
• Most potent and most effective anti-
inflammatory
• Effects not seen immediately (delay 6 or
more hrs)
• Inhaled corticosteroids are used for long
term control
Therapeutic uses
• Endocrine uses:
– Replacement therapy – In
• Acute adrenal insufficiency- Immediate
treatment with hydrocortisone i.v.
• Chronic adrenal insufficiency –
Addison’s disease- Hydrocortisone orally
• Congenital adrenal hyperplasia
– Diagnostic use :
• To test pituitary-adrenal axis function
Contd..
• Nonendocrine uses :
– As antiinflammatory agent in
• Rheumatoid arthritis, osteoarthritis, gout
• Ulcerative colitis and Crohn’s disease
• Inflammatory diseases of eye – Allergic
conjunctivitis, iritis, iridocyclitis
• Several inflammatory/allergic diseases and
eczematous skin diseases
• Cerebral edema, neurocysticercosis
Contd…
• As Immunosuppresive therapy in
– Collagen vascular diseases- SLE,
polyarteritis nodosa, dermatomyositis
– Skin graft and Organ transplantation
– Nephrotic syndrome
– Autoimmune diseases- Hemolytic anemia,
thrombocytopenic purpura, myasthenia
gravis
• Severe allergic reactions-anaphylaxis,
urticaria
Contd..
• Stimulation of lung maturation in
fetus
• In malignancies like
– Haemopoietic malignancies- leukemia
– Hodgkin’s and other lymphomas
• Infective disease- severe lepra reaction,
certain bacterial meningitis, pnemocystis
carinni pnemonia with hypoxia in AIDS
• Lung diseases-Status asthmatics, severe

chronic asthma, aspiration pnemonia and
pulmonary edema from drowning
Important preparations
• Hydrocortisone – Rapid & short acting; used in
– Replacement therapy
– Shock, ac severe br. Asthma, ac. Adrenal insuff.
– Topical & as suspension for enema in U. colitis
• Prednisolone – 4 times more potent & selective;

intermediate action; used in many conditions
• Methylprednisolone- more potent and more selective;

used as retention enema in u. colitis; pulse therapy in rh.
Arthritis, renal transplant, pemphigus etc
Contd..
• Triamcinolone- Highly selective glucocorticoid
& potent than prednisolone, used as
intraarticular injection
• Dexamethasone and betamethasone –
– Very potent, highly selective, long acting
– Used in inflammatory & allergic conditions,
shock, cerebral edema
• Desoxycorticosterone acetate[DOCA]
– It has only mineralocorticoid activity.
Used occasionally for replacement therapy
in Addison’s disease
• Fludrocortisone – a potent
mineralocorticoid having some
glucocorticoid activity as well.
Used for replacement therapy in Addison’s
disease
• Aldosterone – most potent
mineralocorticoid. Not used clinically
because of low oral bioavailability.
• Beclomethasone dipropionate,
budesonide, fluticasone etc are used
by inhalation in asthma, as spray in nasal
allergy.
Adverse effects
• Steroids: the worst drugs for
adverse effects
S Adverse effects
I
D
E
E
F
F
E
C
T Pituitary adrenal suppression
S +
after sudden withdrawal
following long admn
Contraindications
• Peptic ulcer
• Diabetes mellitus
• Hypertension
• Viral and fungal infections
• Tuberculosis and other infections
• Osteoporosis
• Psychosis
• Epilepsy
• CHF
Synthesis Inhibitors and Glucocorticoid
Antagonists
• Aminoglutethimide
MoA: Blocks the conversion of cholesterol to

pregnenolone  reduction in the
synthesis of all hormonally active steroids
Uses: -with metyrapone or ketoconazole to

reduce steroid secretion in pts with
Cushing’s syndrome due to adrenocortical
cancer
Ketoconazole:
- Antifungal agent
- An inhibitor of different hydroxylases;
inhibits steroidogenesis in adrenal
cortex and gonads
Uses:
- treatment of Cushing’s syndrome due to
several causes.
Metyrapone
- 11β-hydroxylase inhibitor
- interfere with cortisol and corticosterone
synthesis.
-Effective in the management of Cushing’s
syndrome
- Only adrenal inhibiting medication that can
be administered to pregnant women with
cushing’s syndrome
Trilostane
Competitive inhibitor of β-hydroxysteroid

dehydrogenase enzyme and therefore interferes
with the synthesis of adrenal and gonadal
hormones
Mitotane
Causes selective atrophy of Zona Fasciculata and
Zona Reticularis. This results in a rapid reduction
in the levels of adrenocorticosteroids
Useful in the treatment of adrenal Ca when
radiotherapy or surgery are not feasible
• Glucocorticoid Antagonist
Mifepristone
• Mineralocorticoid Antagonist
Spironolactone
Eplerenone

Corticosteroids

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Corticosteroids

• Hormones produced by the

Medulla[inner] Adrenaline and NA

Progesterone 17- Hydroxy Andro-

11-Desoxy- 21,β hydroxylase

ALDOSTERONE CORTISOL TESTOSTERONE OESTRADIOL

• Corticosteroids enters the cell as free molecules

 Decreases neutrophils, lymphocytes, eosinophils,

Prolonged use: muscle wasting and

– increased acid and pepsin secretion

– decreased immune response to

• Lung diseases-Status asthmatics, severe

• Prednisolone – 4 times more potent & selective;

• Methylprednisolone- more potent and more selective;

MoA: Blocks the conversion of cholesterol to

Uses: -with metyrapone or ketoconazole to

Competitive inhibitor of β-hydroxysteroid

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