DNB MEDICINE ACADEMICS

2. CORTICOSTEROIDS
By Dr Kiran Bikkad

3. INTRODUCTION
 One of the broadest spectrum drugs in clinical practice
 Active principles isolated & structure ilucited by Kendall(1930)
 Therapeeutic potential & 1st striking results in RA shown by
Hench (1949)
 Nobel prize awarded in 1950

4.  Corticoids are 21 C compounds with steroid nucleus.
 Synthesised in Adrenal cortical cells from cholesterol.
1. Glomerulosa
2. Fasciculata
3. Reticularis

5. STRUCTURE

6. BIOSYNTHESIS

7. ACTIONS
 Maintain fluid electrolyte balance
 Cardiovascular & energy substrate homeostasis
 Prepare body to withstand to noxious stimuli & stress.
 Permissive action
• Eg: On BP, pressor action of adrenaline
 Devided into 2 types
• Glucocorticoid & Mineralocorticoid

8.  Glucocorticoids
• Carbohydrate, Protein & Fat metabolism
• Other actions linked to this
 Mineralocorticoids
• Effects on Sodium, Potassium & Fluid Balance

9. GLUCOCORTICOID
ACTIONS
 Carbohydrate (maintain RBS in starvation)
 Promote glycogen deposition- activate hepatic glycogen synthase
 Promote gluconeogenesis
 Inhibit peripheral Glucose Utilisation
 Increased Glucose Release from liver  Hyperglycemia
 Insulin Resistance & DM like state

10.  Protein (catabolic)
 Protein breakdown
 Muscle wasting
 AA metabolised in liver utilised for gluconeogenesis  Excess
urea  Negative nitrogen balance

11.  Fat
 Permissive
 Promote lipolysis d/t glucagon, GH, Adr, Thyroxine.
 cAMP indused breakdown of TG
 Redistribution of fat (over neck face & shoulder)
 Moon face, Fish Mouth, Buffalo Hump.

12.  Calcium Metabolism
 Inhibit intestinal absorption
 Encrease renal excretion
 -ve Calcium balance  Spongy bones.
 Loss of osteoid from bone
 Lympholysis
 Skin thinning

13.  Water Excretion
 Independent of sodium transport action
 Aldosterone maintains GFR, so in absence of it, risk of water
intoxication+.

14.  CVS
 Restrict capillary permeability & maintain arteriolar tone &
myocardial contractility
 Permissive effect on pressor effect of Adr.
 So Cautiously used in HTN

15.  Skeletal Muscles
 Optimum level required for normal muscle activity
 Weakness in Both Hypo & Hypercorticism
 Hypo:
• Hypodynamic circulation  decreased work capacity & weakness
 Hyper:
• Excess mineralocorticoid action Hypokalemia  weakness.
• Excess Glucocorticoid action  Muscle wasting  myopathy 
weakness.

16.  CNS
 Mild Euphoria
 Increased motar activity
 Insomnia
 Anxiety/depression
 High doses lower seizure threshold so cautious use in Epileptics

17.  Stomach
 Increase gastric acid & pepsin secretion
 Increases peptic Ulcers

18.  Lymphoid Tissue & Blood Cells
 Lymphocyte destruction increased (T>B)
 Increase : RBC, Neutrophills, Platelets
 Decrease : Lymphocyte, Eosinophills & Basophills (d/t
sequastration in tissue & normalise after 24 hours)

19.  Inflammatory Response
 Non specific
 Suppress all components & stages of inflammation

20.  Early response
1. Increased capillary permeability
2. Local exudation
3. Cellular infiltration
4. phagocytic activity
 Late response
1. Proliferation
2. Collagen deposition
3. Fibroblastic activity
4. Scar formation

21.  Mechanism of action not fully understood
 Induces synthesis of lipocortin  inhibits phospholipase A2
 Release of arachidonic accid & PAF blocked  Ecosanoids (PGs,
TXs, LTs) & PAF not produced. (PROINFLAIMATORY)
 Inhibit production of IL-1 from monocyte & macrophages 
Activation T Lymphocytes, fibroblasts, & production of PGs & acute
phase reactants attenuated.
 Inhibits TNF from Phagocytes.
 Inhibits formation of fibrinogen activator by Macrophages & action
of Migration Inhibitory Factor (MIF).

22.  Immunological & Allergic Response
 By suppression of recruitment of leucocytes at the site of
contact with antigen  no inflammatory response to immunological
injury
 CMI suppressed more involving T lymphocyte.
• E.g. :- Delayed Hypersensitivity & Graft rejection
 Inhibit IL 2 Formation  T cell proliferation & suppression of
NK cells.

23. MINERALOCORTICOID
ACTION
 Principle Action : enhance Sodium Reabsorption in DCT ,
Associated potassium & proton excretion.
 Deficiency  unable to absorb Na+  Dilutional Hyponatremia
 Cellular Hydration  Decreased Blood Volume & raised
Haematocrit  circulatory collapse & asso. Hyperkalaemic Acidosis.

24. PHARMACOKINETICS
 All are effective by oral route except DOCA
 Metabolised by LIVER (Hepatic Microsomal Enzymes)
 Excreted in Urine
 Synthetic steroids are more resistant to metabolism & are long acting.
 Phenobarbitone & Phenytoin induce metabolism of steroids &
decrease therapeutic effect
 Hydrocortisone
1. Very High 1st pass metabolism
2. 90/5 bound to plasma protein (Transcortin) & Albumin.

25. PREPERATION & DOSE
 Hydrocortisone (cortisol)
 Rapid & short action (T1/2 <12 hrs)
 Dose :
1. 100 mg i.v. bolus & 100mg 8 hourly infusion in Shock, Status
Asthmaticus & Acute adrenal insufficiency
2. 20 mg (morning) + 10 mg (afternoon) orally as Replacement
Therapy.
3. As suspension for enema In Ulcerative Colitis.

26. PREDNISOLONE
 4 times more potent than hydrocortisone
 More selective glucocorticoid activity
 Dose :
 Oral 5-60 mg/day
 i.m. / i.v. 10-40mg/day

27. METHYL PREDNISOLONE
 Slight more potent & selective
 Dose : 4-32mg/day
 Use : as retention enema in UC
 High dose pulse therapy in non responding RA, Renal transplant (1gm
i.v. every 6-8 weekly)
 MOA of MPPT : initial effect d/t anti-inflaimmatory action & long
term benefit d/t temporary switching off immunodamaging process

28. DEXAMETHASONE
 Very potent & highly selective glucocorticoid
 Causes marked Pituitary Adrenal suppression
 No fluid retention & HTN.
 Dose : 0.5-5mg/day oral
 4-20mg/day i.v. or i.m.

29. BETAMETHASONE
 All properties & doses same as dexa but Little more potent

30. DOCA
 Des oxy corticosterone acetate
 Only mineralocorticoid activity(100%)
 Use : As replacement therapy in Addison's disease 2-5mg
sublingual & 10-20 mg i.m. once or twice weekly.

31. FLUDROCORTISONE
 More potent mineralocorticoid
 Minimal glucocorticoid activity
 Same as Replacement therapy in Addisons disease :- 50-200
mocro.gm/day

32. ALDOSTERONE
 Most potent mineralocorticoid
 Not used clinically bcoz low bioavailability & difficulty in
regulation

33. RELATIVE ACTIVITY

34. USES
 Replacement Therapy
1. Adrenal Insufficiency
1. Acute
2. Chronic
2. Congenital Adrenal Hyperplasia

35. NON ENDOCRINE
DISEASES
 Arthitides
1. Rheumatoid Arthritis :-
1. COBRA REGIMEN (SULFASALAZINE 2 gm/day, MTX
7.5mg/week, prednisolone go-7.5mg.day over 5 months)
2. Osteorthritis
3. Rheumatic Fever
4. Gout

36. COLLAGEN DISEASE
1. SLE
2. PAN
3. Dermatomyositis

37. SEVERE ALLERGIC
REACTIONS
1. Anaphylaxis
2. Angioedema
3. Urticaria
4. Serum Sickness

38. AUTOIMMUNE DISEASES
1. Haemolytic Anaemia
2. Thrombocytopenia
3. Active Chronic Hepatitis
4. Myasthenia Gravis as adjunctive to neostigmine

39. LUNG DISEASES
1. Br Asthma
2. ILD
3. Lung maturation & surfactant production

40. EYE DISEASES
1. Allergic Conjunctivitis
2. Iritis
3. Iridocyclitis
4. Keratitis

41. SKIN DISEASES
 Eczema
 Pemphigus vulgaris
 Exfoliative dermatitis
 Steven Johnson Syndrome

42. INTESTINAL DISEASES
 Ulcerative Colitis
 Crohn’s disease
 Coeliac Disease

43. MALIGNANCIES
 Lymphomas :
1. Hodgkin's
2. ALL, etc.
 Breast carcinoma (HR)

44. OTHER
 CEREBRAL EDEMA d/t tumour, TB meningitis
 ORGAN TRAANSPLANT
 SKIN ALLOGRAFT
 SHOCK

45. ADVERSE EFFECTS
 Cushing habitus : moon face, fish mouth, buffalo hump
 Fragile skin with striae
 Hyperglycemia
 Muscle weakness
 Susceptibility to infection
 Delayed wound healing

46. ADVERSE EFFECTS
 Osteoporosis
 Peptic ulcers
 Cataract posterior subcapsular
 Glaucoma
 Mannic psychosis
 Supression of HPA axis

47. BUFFALO HUMP

48. MOON FACE

49. FISH MOUTH

50. C/I
 Peptic ulcer
 Uncontrolled DM/HTN
 Pregnancy
 Osteoporosis
 Herpes simplex keratitis
 Psychosis
 Epilepsy
 Renal failure

51. THANK YOU