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Corticosteroids
The adrenal gland has cortex and medulla
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Adrenal medulla secretes adrenalin and noradrenalin
SYNTHESIS
The corticoids (both gluco and mineralo) are 21 carbon compounds having a cyclopentanoperhydrophenanthrene (steroid) nucleus
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Synthesis
and release of glucocorticoids is controlled by pituitary ACTH which in turn is stimulated by corticotrophin
releasing factor CRF) produced by hypothalamus, Glucocorticoids have negative feedback control on ACTH
and CRF secretion
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There is a diurnal variation in the rate of
release of ACTH and cortisol
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Long term use of corticosteroids in large doses will decrease ACTH secretion and
gradually use adrenal cortical atrophy
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The steroid
receptor complex get activated, which then enters the nucleus, binds to glucocorticoid response elements on
DNA and regulate protein synthesis and produce response

HRTin acute adrenal
Insufficiency
Status asthmaticus
Anaphylactic shock

Antiinflammatory
Immunosuppressant
Triam-more potent

Long acting
HRT-Addisons disease
Antiinflammatory
Flu-e hydrocortisone-AD
Immunosuppressant
Cerebral edema-in neoplasm

LONG ACTING-Beclomethasone,Budesonide,Fluticasone-used as inhalation in bronchial asthma, COPD
Glucocorticoids – Hydrocortisone and cortisone, have predominant liver glycogen deposition and
gluconeogenic effect
Minera/ocorticoid Aldosterone and Desoxy corticosterone , produce sodium water retention
Mineralocorticoid actions
The principal mineralocorticoid (aldosterone) action is enhancement of Na+ reabsorption from the distal
convoluted tubule in kidney with an associated increase in K+ and H+ excretion
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MOA:The action of aldosterone is exerted by gene mediated increased transcription of m-RNA in renal tubular
cells which directs synthesis of proteins (aldosterone-induced proteins- AIP)
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More of these
proteins are synthesized
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They also translocate Na+K+ATPase to the basolateral membrane
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All these changes promote Na+ reabsorption
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The intercalated cells secrete more H+ due to stronger
lumen negative potential
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Glucocorticoid actions
1
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Protein metabolism
They also cause protein breakdown and amino acid mobilization from peripheral tissues lymphoid tissues such
as muscle,skin,bone(negative nitrogen balance) ,which is utilised for gluconeogenesis
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Wound healing and fibrosis are also inhibited
3 Fat metabolism They promote lipolysis due to glucagon, growth hormone, Adr and thyroxine,cAMP induced
breakdown of triglycerides is enhanced Prolonged use of glucocorticoids causes redistribution of body fat which
is deposited over face, neck and shoulder producing ' moon face' , ' fish mouth ' and 'buffalo hump'
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Calcium metabolism Glucocorticoids inhibit intestinal absorption and enhance renal excretion of Ca2+
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Spongy bones
(vertebrae,ribs, pelvis, etc
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5
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Mild mineralocorticoid action, prolonged use may produce edema and
hypertension
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CVS Glucocorticoids play a permissive role for the prcssor action of Adr and angiotensin, as well as a
permissive role in the development of hypertension
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Skeletal muscles Optimum level of corticosteroids is needed for normal muscular activity
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8
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insomnia
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Patients of
Addison's disease suffer from apathy, depression and occasionally psychosis
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Stomach Secretion of gastric acid and pepsin is increased (inhibit PG synthesis)- may aggravate peptic ulcer
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Foetal lungs: Glucorticoids promote structural and functional maturation of foetal lungs near term
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11
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However, they have a marked lympholytic action
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12
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This is the basis of most of their clinical uses
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This includes attenuation of- increased capillary
permeability, local exudation, cellular infiltration, phagocytic activity and late responses like capillary
proliferation, collagen deposition, fibroblastic activity and ultimately scar formation
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heat, swelling and pain arc suppressed
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PAF through indirect inhibition of phospholipase A2 by producing protein lipocortin
Corticoids are only palliative; do not remove the cause of inflammation; the underlying disease continues to
progress while manifestations are dampened
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Indiscriminate use of corticoids is hazardous
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Immunosuppressant effect
Glucocorticoids inhibit both B cell and T cell function and this results in impairment of humoral and cell
mediated immunity
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Factors involved may be inhibition of I L- 1 release from macrophages;inhibition of IL-2 formation and action
→ suppression of T cell proliferation and natural killer cells, etc
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Absorption
into systemic circulation occurs from topical sites of application as well,
Water soluble esters, e
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hydrocortisone hemisuccinate, dexamethasone sod
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v
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Insoluble esters, e
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hydrocortisone acetate,
triamcinolone acetonide cannot be injected i
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, but are slowly aborbed from i
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site and produce more
prolonged effects
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Hydrocortisone is 90% bound to plasma protein, mostly to a specific cortisol-binding globulin (CBG or
transcortin) as well as to albumin
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The synthetic derivatives are more resistant to metabolism and are longer acting
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to decrease their therapeutic effect
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A
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Gradual rise in BP occurs due to excess glucocorticoid action
B
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Cushing's habitus: Abnormal fat distribution causes peculiar features with rounded face, narrow mouth,
supraclavicular hump (buffalo hump), obesity of trunk with relatively thin limbs
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Fragile skin, purple striae-typically on thighs and lower abdomen, easy bruising, telangiectasis
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3
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4
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arm, pelvis
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Myopathy occurs on long term use
5
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Latent tuberculosis may flare; opportunistic infections like fungal,viral and bacterial infections with low grade
pathogens (Candida,etc
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Inhalational steroids cause local irritation and fungal infection in the upper
respiratory tract,can be prevented by the use of spacer and by rinsing the mouth after inhalation
6
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7
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8
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Compression fractures of vertebrae
and spontaneous fracture of long bones can occur, especially in the elderly
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Ischaemic necrosis of head of femur, humerous, or knee joint can occur
9
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11
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Psychiatric disturbances: mild euphoria frequently occurs, may rarely progress to manic
psychosis
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14
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Stoppage of exogenous steroid precipitates
withdrawal syndrome consisting of malaise, fever, anorexia, nausea, postural hypotcnsion, electrolyte
imbalance, weakness, pain in muscles and joints
Reactivation of the disease for which the steroid was used
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Measures that minimise HPA axis suppression are:
(a) Use shorter acting steroids (hydrocortisone, prednisolone) at the lowest possible dose
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(c) Give the entire daily dose at one time in the morning
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Replacement therapy
1
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Hydrocortisone ( I 00 mg) or dexamethasone
(8- 16 mg) are given i
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Later, cause of adrenal insufficiency should be treated
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Chronic adrenal insufficiency (Addison's disease) Hydrocortisone given orally, along with adequate
salt and water
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Congenital adrenal hyperplasia (Adrenogenital syndrome) It is a familial disorder due to genetic deficiency
of steroidogenic enzymes, mostly 2 1-hydroxylase
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There is compensatory increase in ACTH secretion
Treatment - hydrocortisone 0
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Pharmacotherapy (for nonendocrine diseases)
Systemic as well as topical corticosteroids have widest spectrum of medicinal uses due to their antiinflammatory
and immunosuppressivc properties
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Arthritides
( i) Rheumatoid arthritis: Corticosteroids are indicated only in severe cases as adjuvants to NSAIDs and
DMARDS when distress and disability persists
(ii) Osteoarthritis:rarely used,intraarticular injection of a steroid may be given to control an acute exacerbation
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(iii) Rheumatic fever: Corticoids are used only in severe cases with carditis and CHF with the aim or rapid
suppression of symptoms
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Collagen diseases Most cases of systemic lupus erythematosus, polyarteritis nodosa, dermatomyositis
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3
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Autoimmune diseases Autoimmune haemolytic anaemia, idiopathic thrombocytopenic purpura, active
chronic hepatitis respond to corticoids
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Bronchial asthma Early institution of inhaled glucocorticoid therapy is now recommended in most cases
Systemic corticosteroids are used for:
• Status asthmaticus:
• Acute asthma exacerbation
• Severe chronic asthma
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Other lung diseases Corticosteroids benefit aspiration pneumonia and pulmonary edema from drowning
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Infective diseases They are indicated in conditions like severe forms of tuberculosis (miliary
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), severe lepra reaction, certain forms of bacterial meningitis and Pneumocystis carinii pneumonia with
hypoxia in AIDS patients
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Eye diseases: Corticoids arc used in allergic conjunctivitis, iritis, iridocyclitis,keratitis, etc
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Skin diseases : Topical corticosteroids are effective in many eczematous skin diseases
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exfoliative dermatitis, Stevens-Johnson
syndrome and other severe afflictions
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Intestinal diseases Ulcerative colitis, Crohn's disease, coeliac disease are inflammatory bowel diseases
11
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12
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v
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13
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14
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Septic shock
16
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Moreover, corticosteroids reduce peripheral T4 to T3 conversion
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v
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Peptic ulcer
2
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Hypertension
4
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Tuberculosis and other infections
6
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Herpes simplex keratitis
8
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Epilepsy
10

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