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• The adrenal produces various
classes of hormones, each of which
aid in dealing with the stress faced by
animals and people almost daily
• At least two of these groups

Glucocorticoids and

necessary for or
lifecorticoids refer
to natural
gluco- and mineralo-corticoids and


Physiological and Pharmacological actions
Pharmacokinetics and preparations
Uses – therapeutic and diagnostic
Dosage schedule and withdrawal
Adverse reactions and contraindications
Precautions during therapy


An inner medulla, is a

source of catecholamine –
adrenaline and nor-adrenaline

An outer cortex, which
secretes several classes of
steroid hormones including
Glucocorticoids and

Regulation of Synthesis • Synthesized and released under influence of ACTH . Pituitary (HPA axis) • Regulated by CRH from hypothalamus and by feedback levels of blood concentrations .Ant.

Control by circadian rhythm (Diurnal rhythm) – morning rise Stress: hypoglycaemia. 2. .Regulation of Synthesis . physical stress etc.Others 1.

Glucocorticoids .MOA  Not stored:      rate of synthesis = rate of release Synthesize rhythmically and controlled by irregular pulses of ACTH. influenced by light and major pulses occur early in the morning and after meals Glucocorticoids act via their receptors located in nucleus (GR) GRs are widely distributed and located almost in all cells of the body They are made up of almost 800 amino acids .

MOA        GR receptors are located in the cytoplasm One GR receptor has a DNA binding domain and a ligand binding domain along with stabilizing proteins (HSP 90 and HSP 70) This receptor is incapable of activating transcription Binding of free steroid molecule to GR forms an unstable compound Therefore HSP and other proteins get dissociated The S+GR complex enters the nucleus and binds to Glucocorticoids response element (GRE) on gene and regulate transcription by RNA polymerase II and others The resulting mRNA is transported to cytoplasm for production of protein and bring about final response .Glucocorticoids .

Glucocorticoids .MOA .

lipid and protein metabolism Fluid and electrolyte balance Normal functioning of CVS.g. kidneys.sympathomimetic amine) .. immune system. skeletal muscles and nervous system Provides resistance to stress and noxious stimuli and environmental changes Permits and facilitates the actions of other hormones  Direct Actions  Permissive Actions • • • • Lipolytic effects Effect on BP Effect on bronchial muscles (e.Actions Numerous and widespread actions:      Carbohydrate.

expansion of ECF. hyperkalamia. sweat gland and salivary gland Deficiency of mineralocorticoid action leads to – dilutional hyponatraemia.Actions of Corticosteroids Mineralocorticoid       Aldosterone is the prototype of mineralocorticoid effects Acts on the distal tubule to enhance absorption of Na+ Increase excretion of K+ and H Similar effects occur in colon. massive loss of Na+ and decreased ECF volume (essential for survival) Hyperaldosterinism: Positive Na+ balance. . acidosis. hypokalaemia. increased plasma Na. alkalosis and progressive rise in BP – hypertension. myocardial fibrosis etc.

increase protein breakdown and activate lipolysis – form amino acids and glycerol for gluconeogenesis All these results in    Diabetes like stat resistant to insulin – increased glucose release from liver + decreased peripheral glucose utilization Negative Nitrogen balance (catabolic effect) – amino acid used up in gluconeogenesis – increased urea production Mobilization of amino acids – muscles.Glucocorticoid actions Carbohydrate & protein metabolism     Profound effect on carbohydrate and protein metabolism – aimed at protecting glucose dependent tissues (brain and heart) Promotes glycogen deposition in liver and stimulate it to form glucose from amino acids – gluconeogenesis In peripheral tissues decreases utilization of glucose. thinning of bone and skin .

Actions: Carbohydrate and protein metabolism Negative nitrogen balance & hyperglycaemia  Gluconeogenesis   Peripheral actions (mobilize AA & Hepatic actions glucose and glycogen)  Peripheral utilization of glucose  Glycogen deposition in liver (activation of hepatic glycogen synthase) .

but in face and neck predominant action – fat deposition . + Glucocorticoids mediated increased insulin = net result is insulin mediated lipogenesis and fat deposition Peripheral adipocytes are less sensitive to insulin. glucagons.Fat Metabolism   Redistribution of fats in different areas of the body Due to permissive facilitation of effects of other agents – GH. Adr. thyroxine and insulin    Deposition of fats in face. neck and shoulder – moon face/buffalo hump Glucocorticoids facilitated hormone sensitive lipolysis action of GH and Adr.

in adrenal insufficiency capacity to excrete water is lost – water intoxication Normal muscular activity needs Glucocorticoids at its optimum level Excess level leads to muscular weakness and wasting Muscular weakness occurs in both Hypocorticism (due to hypodynamic circulation) and hypercorticism – due to hypokalaemia CNS:    Euphoria – in pharmacological doses Addison's disease – apathy. depression and psychosis High doses – induce seizure .Actions of Glucocorticoids  Water excretion:   Calcium Balance:   Decrease absorption of Ca++ in GIT and increased excretion – calcium depletion .osteoporosis Skeletal muscle:     Glucocorticoids play important role in maintaining normal GFR .

monocytes. eosinophils and basophils but increases Polymorphs .Actions of Glucocorticoids  CVS: Permissive role on pressor effect with Adr and angiotensin     Maintain tone of arterioles and myocardial contractility Adrenal insufficiency leads to low cardiac output and arteriolar dilatation and poor response to adrenaline Cardiovascular collapse – along with mineralocorticoids Blood and lymphoid tissues:     Destruction of lymphoid tissue – modest in normal persons In presence of malignancy of lymphatic cells – lytic actions are significant (apoptosis) – used in lymphomas (Basis of Use) Minor effects on haemoglobin and RBCs – protect against haemolysis of RBCs – Increase in number of RBCs Decreases the numbers of circulating lymphocytes.

hypersensitivity Underlying cause of disease is not corrected Reduction in cardinal signs of inflammation Anti-inflammatory effects are non—specific and covers all components of inflammation:   Effects on concentration.Glucocorticoids – anti-inflammatory and immunosuppressive effects     Suppress inflammatory response to all noxious stimuli: Pathogens. LT and PAF synthesis that results from activation of phospholipase A2 Basis of exogenous use of most clinical uses .physical and immune mediated stimuli. chemical. distribution and functions of peripheral leukocytes – increased neutrophils & their activity In macrophages: reduction of arachidonic acid metabolites (mediators) like PG.

3. – fibroblast proliferation and T-lymphocyte function – interference with chemotaxis .macrophage into affected area & elaboration of chemotactic substances Lipocortin: decreased production of PG.Glucorticoids . GM-CSF etc. LT and PAF Negative regulation of COX 2: inducible PG production Negative regulation of genes in cytokines of macrophages. endothelial cells and lymphocytes: production of IL (1. 2. TNFα. 6).Multiple Mechanisms     Recruitment of WBC & monocyte .

Contd.osteoporosis Decreased IgG production Decreased generation of induced nitric oxide .       In endothelial cells-Endothelial leucocyte adhesion molecule (ELAM) and other CAM are inhibited – adhesion and localization of leucocytes interfered Release of histamine from basophils is inhibited Decreased production of collagenase – prevention of tissue destruction Decreased functioning of osteoblasts and increased activity of osteoclastic activity .

Corticosteroids Lipocortin Phospholipids Phospholipase A2 Arachidonic acids Cycylooxygenase lipoxygenase Leukotriene PAF by lipocortin Prostaglandins. Thromboxane Prostacyclins .

sensitisation of T lymphocytes etc. . delay revascularization.Immunosuppressive & anti-allergic actions     Suppresses all types of hypersensitivity & allergic phenomenon At High dose: Interfere with all steps of immunological response Causes greater suppression of CMI (graft rejection & delayed hypersensitivity) Transplant rejection: antigen expression from grafted tissues.

Glucocorticoids – Anti-inflammatory and Immunosuppressive effects .

Important agents  Injectable: Betamethasone Prednisolone Hydrocortisone  Oral: Betamethasone Prednisolone Methylprednisolone  Fludricortisone Prednisone Topical: Betamethasone Flucinolone  Dexamethasone Methylprednisolone Triamcinolone Clobetasol Mometasone Inhalation: Beclomethasone Flunisolode Budesonide .

asthma and inflammatory bowel disease In organ transplant patients and those with autoimmune disorders corticosteroids are used for their immunosuppressive effects .Therapeutic uses    Physiologic doses of Corticosteroids are used for replacement therapy in primary and secondary adrenal insufficiency such as Addison`s disease Supraphysiologic doses are used for their antiinflammatory effects in arthritis.

Hemorrhage and AIDS  Congenital adrenal hyperplasia  Congenital disorder due to deficiency of 21hydroxylse enzyme – no cortisol but ACTH – increased androgen production CAH .Replacement Therapy  Adrenal insufficiency – acute/chronic     Abrupt withdrawal of steroid therapy Chronic infections – Tuberculosis Autoimmune adrenal disease Surgery.

dexamethasone can be used)  Chronic adrenal insufficiency     Hydrocortisone Prednisolone or dexamethasone – long acting Fludrocortisone for mineralocorticoid effects Congenital adrenal hyperplasia  Hydrocortisone 0.Replacement Therapy  Acute adrenal insufficiency   IV replacement of sodium chloride and fluid IV hydrocortisone 100 mg stat followed by100 mg every 8 Hrs – maximal daily rate of secretion (alternatively.6 mg/kg in divided doses – to maintain feedback suppression .

intra-articular injection Rheumatic fever – severe cases with carditis and CHF Gout – NSAID failed cases and colchicine failed cases – intra-articular injection Vasculitic disorders: Polyarteritis nodosa .Anti-inflammatory Uses  For suppression of inflammatory components in –      Rheumatoid arthritis – as adjuvant with NSAIDs in severe cases Osteoarthritis – NSAIDs.

Intra-articular Steroids Can be used in inflammatory Non-inflammatory diseases • Knee joint • Shoulder joint • Tennis elbow • Carpal tunnel syndrome .

Autoimmune diseases ITP  Autoimmune haemolytic anaemia  Idiopathic thrombocytopenic purpura  Active chronic hepatitis. alcoholic hepatitis (Prednisolone 1-2 mg/kg/day given till remission followed by gradual withdrawal or low dose maintenance) .

Renal diseases SLE  Nephrotic syndrome in children  Renal disease secondary to SLE  Renal sarcoidosis  Glomerulonephritis – membranous type (Life saving importance – usually given in large doses followed by tapering to maintenance dose) .

azathioprine  For prolonged use:  Prednisolone or methylprednisolone are used    Intermediate duration of action Can be easily tapered Can be converted to an alternate regime .Organ Transplant  Combined with other immunosuppressants – cyclosporin.

Allergic Disorders    Exhibit a delayed response in allergies (1-2 hrs even in IV injection) In anaphylaxis. angioneurotic oedema and serum sickness etc. drug allergies –   Allergic reactions can be suppressed by corticosteroids as supplements Intranasal administration in allergic rhinitis budesonide and flunisolide . bee sting. – adrenaline is the choice Seasonal allergies.

Bronchial Asthma   The increased recognition of the immunological and inflammatory nature of Bronchial asthma has led to the use of corticosteroids In severe asthma attacks IV hydrocortisone Oral prednisolone  Methylprednisolone Acute attacks: *Inhaled beclmethasone. flunisolide alone or combined with beta-2 agonists/ipratropium *Oral steroids . budesonide.

Infectious Diseases  Indicated only in severe infective diseases to tide over crisis or prebent complictions      AIDS and pneumocystis carinii pneumonia In haemophilus influenza meningitis to reduce neurological complications Tubercular meningitis Lepra reaction Scepticaemia Lepra reaction .

fulminant bacterial infections. Systemic steroids for the posterior chamber Dexamethasone topical 0.Ocular Diseases       Important drug therapy for suppressing inflammation in eye and preservation of sight Topical instillations are used for conditions of the anterior chamber – allergic conjunctivitis. fungal infections and injuries .1% Prednisolone oral Contraindicated in viral. iritis. iridocyclitis and keratitis etc.

Skin Diseases Pemphigus vulgaris  The largest application of steroid therapy  Topical forms are widely used in many eczematous skin diseases  Systemic therapy are also required and may be life saving in    Pemphigus vulgaris Exfoliative dermatitis Stevens-Johnson syndrome .

GIT  Inflammatory conditions of intestine like Ulcerative colitis  Crohn`s disease  Coeliac disease (oral therapy or retention enema with hydrocortisone)   May mask the major complications like perforation and peritonitis .

Malignancy Hodgkin`s lymphoma  Essential for combined chemotherapy of    Acute lymphatic leukemia Hodgkin's and other lymphomas Hormone responsive breast carcinoma  Symptomatic relief in other advance malignancies by improving appetite and controlling secondary hypercalcaemia .

Cerebral Oedema  Cerebral oedema due to tumors (neoplasms)  Traumatic and poststroke oedema (?) (Dexamethasone or betamethasone is preferred because no Na+ retaining activity)  Other CNS conditions .spinal chord injury. Bell`s palsy and neurocysticercosis  (Oral Prednisolone is the preferred drug) .

pulmonary oedema from drowning  Hyperthyroidism – thyroid storm .Other Uses  Antiemetic – with ondansetron  Acute mountain sickness  Aspiration pneumonia.

Adverse Effects  Two types:   From abrupt withdrawal Chronic therapeutic use of high dose  Withdrawal    Flare up of underlying disease Suppression of HPA axis and acute adrenal insufficiency Increased ICT and papilloedema .

Adverse Effects Cushing`s habitus .

humorous etc.Other Important Adverse Effects           Fluid and Electrolyte Disturbance – Na and water retention Precipitation of Diabetes mellitus – hyperglycemia Increased susceptibility to infections – immune response suppression Peptic ulceration – bleeding & perforation Osteoporosis – flat spongy bones Osteonecrosis – avascular necrosis of head of femur. Myopathy – weakness of muscles Cataract – posterior sub capsular Glaucoma – prolonged topical therapy Growth retardation – in children .

the patient may be switched to a shorter acting agent for further tapering Intermediate acting corticosteroids allow for more flexible dosing schedule      Have potent glucocorticoid effects Causes lesser suppression of HPA axis Causes less GIT irritation Preferred for oral therapy Prednisolone. are available in a number of dosage forms .5-5 mg of prednisolone equivalent daily Once the GC dose is reduced to 5 mg of prednisolone equivalent. methylprednisolone and triacinolone have a half life of 12-36 Hrs.Withdrawal of Steroid Therapy    Taper the dose to reduce GC dose by 2.

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