Your SlideShare is downloading. ×
0
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Pharmacology of corticosteroids
Upcoming SlideShare
Loading in...5
×

Thanks for flagging this SlideShare!

Oops! An error has occurred.

×
Saving this for later? Get the SlideShare app to save on your phone or tablet. Read anywhere, anytime – even offline.
Text the download link to your phone
Standard text messaging rates apply

Pharmacology of corticosteroids

2,197

Published on

Presentation for Medical undergraduates for teaching pharmacology. It deals with Physiology of steroid hormones and their action along with agents which are used therapeutically with their action, …

Presentation for Medical undergraduates for teaching pharmacology. It deals with Physiology of steroid hormones and their action along with agents which are used therapeutically with their action, adverse effects and therapeutic uses.

Published in: Health & Medicine, Technology
4 Comments
23 Likes
Statistics
Notes
No Downloads
Views
Total Views
2,197
On Slideshare
0
From Embeds
0
Number of Embeds
0
Actions
Shares
0
Downloads
11
Comments
4
Likes
23
Embeds 0
No embeds

Report content
Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
No notes for slide

Transcript

  • 1. CORTICOSTEROIDS Dr Mayur Chaudhari Assistant Professor Department of Pharmacology Government Medical College, Surat
  • 2. Steroids are fast catching up with antibiotics as the most abused class of drugs today 2
  • 3. HISTORY  1855 – Thomas Addison  1856 – Charles-Edouard Brown-Sequard  1932 – Harvey Cushing  1936 – Edward Kendall & Tadeus Reichstein.  1949 – Phillip Hench  1954 – Aldosterone  1955 - ACTH 3
  • 4.  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 Mineralocorticoids are necessary for life .  Corticosteroids or corticoids refer to natural glucoand mineralo-corticoids and their synthetic analogues. 4
  • 5. LEARNING OBJECTIVES  Biosynthesis  Actions  Pharmacokinetics and Preparations  Uses  Dosage schedule and withdrawal  ADRs and Contraindications  Precautions during therapy  Contraindications 5
  • 6. ANATOMY 6
  • 7. BIOSYNTHESIS OF ADRENAL HORMONES Mineralocorticoids Glucocorticoids Sex Hormones 11-OH Pregnenolone Dehydroepiandrosterone DHEA Cholesterol ACTH Pregnenolone 11 α OH 11 α OH 17,20 lyase 11-OH Progesterone 17,20 lyase Progesterone 11- Deoxy Corticosterone Androstenodione 11- Deoxy Cortisol Testosterone Cortisol Corticosterone AT II Dihydrotestosterone Aldosterone Estradiol 7
  • 8. REGULATION  Synthesized and Released under influence of ACTH and Pituitary.  Regulated by CRH from hypothalamus and by feedback levels of blood concentrations 8
  • 9. HPA AXIS 9
  • 10. REGULATION Circadian rhythm 10
  • 11. MECHANISM OF ACTION 11
  • 12. ACTIONS • Effect on Na+ Mineralocorticoid • Effect on K+ • Fluid Balance Glucocorticoid • Carbohydrate • Protein and Fat • Other Activities 12
  • 13. MINERALOCORTICOID ACTIONS  Enhanced absorption of Na+ from DT  increased excretion of K+ and H+.  Similar action on colon, sweat gland and salivary gland. 13
  • 14. EXTREMES OF ALDOSTERONE  Dilutional hypernatremia,  Hyperkalamia, acidosis,  massive loss of Na+ and decreased EFC volume  Positive Na+ balance, expansion of ECF,  Increased plasma Na, hypokalemia, alkalosis hypertension  myocardial fibrosis 14
  • 15. GLUCOCORTICOID ACTIONS CARBOHYDRATE METABOLISM  Glycogen deposition in liver  Gluconeogenesis  Inhibit glucose utilization  Hyperglycemia  Insulin resistance, DM like state 15
  • 16. PROTEIN METABOLISM  Breakdown of protein  Mobilize Amino Acid from peripheral tissues  Muscle wasting, lympholysis, loss of osteoid from bone  Thinning of skin  Excess urea production – Negative nitrogen balance  Increase uric acid excretion 16
  • 17. FAT METABOLISM  Permissive action due to Glucagon, Growth Hormone, Adrenaline and Thyroxine – Lipolysis.  Increased breakdown of triglycerides.  Redistribution of body fat – Moon face, Buffalo Hump, Fish Mouth. 17
  • 18. CALCIUM METABOLISM  Inhibition of intestinal absorption and promotion of excretion  Loss of calcium from bone.  Negative calcium balance  Spongy bones – more sensitive. 18
  • 19. WATER EXCRETION AND STOMACH  Maintain normal GFR  In adrenal insufficiency capacity is lost – water intoxication  Gastric acid and pepsin secretion enhanced  Aggravate peptic ulcer 19
  • 20. CARDIOVASCULAR SYSTEM  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 20
  • 21. SKELETAL MUSCLES  Hypocorticism: Decreased work capacity, weakness  Hypercorticism: Excess Mineralocorticoid .Hypokalemia – Weakness.  Excess glucocorticoid : Muscle wasting, weakness and myopathy 21
  • 22. CENTRAL NERVOUS SYSTEM  Mild euphoria, increased motor activity  Insomnia, hypomania or depression  Apathy, depression and psychosis in Addison’s disease.  Maintenance of perceptions and excitability of neurons  Lowers seizure threshold 22
  • 23. LYMPHOID TISSUE  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, monocytes, eosinophils and basophils but increases Polymorphs 23
  • 24. INFLAMMATION  Prevent migration of leucocytes  Prevent chemotaxis and lysosomal enzyme synthesis  Diminish production of PGs, LTs, PAF and histamine release  Stabilize lysosomal membrane preventing spillage of lysosomal enzymes 24
  • 25. INFLAMMATION  Suppress inflammatory response to all noxious stimuli at all stages  Cardinal signs of inflammation inhibited  Root cause remain intact  Favor spread of infection  Interfere with healing and scar formation  Silent perforation 25
  • 26. IMMUNOLOGICAL ACTION  Inhibit function of macrophages, Reduce ability to respond to antigen  Inhibit activation of cytotoxic T lymphocytes, cause lysis of T Lymphocytes  Effects of complement are inhibited  Prevent Homograft rejection 26
  • 27. IMMUNOLOGICAL ACTION  Impair immunological competence  Suppress all types of hypersensitization and allergy.  Suppression of CMI – delayed hypersensitivity, graft rejection  Inhibit release of IL1 from macrophages, IL2 formation  Suppression of natural killer cell 27
  • 28. MISCELLANEOUS  Uricosuric action  Nonspecific antipyretic  Structural and functional maturation of fetal lung 28
  • 29. PHARMACOKINETICS  Therapeutically given by various routes – orally, IM, IV, topically  Hydrocortisone undergoes high first pass metabolism  Oral bioavailability of synthetic corticoids is high  Both, endogenous and therapeutically administered GC are bound to Corticosteroid Binding Globulin (CBG) 29
  • 30. PHARMACOKINETICS  Synthetic steroids have to undergo reduction in liver to active compounds  Metabolized in liver and excreted in urine  Exogenously administered hydrocortisone has t1/2 of 1.5 Hrs 30
  • 31. HYDROCORTISONE  Rapid but short acting with significant Mineralocorticoid activity  Used for replacement therapy, shock,  Status asthmaticus and adrenal insufficiency  Topically and as enema for ulcerative colitis 31
  • 32. PREDNISOLONE  More potent than hydrocortisone, more GC activity  Intermediate duration of action  Less HPA axis suppression  Used for allergic, inflammation  autoimmune diseases, malignancy 32
  • 33. METHYLPREDNISOLONE  More potent and more selective  Retention enema in ulcerative colitis  Pulse therapy in non responsive RA  Renal transplant, pemphigus  Minimal suppression of HPA axis. 33
  • 34. TRIAMCINOLONE  Potent and selective glucocorticoid  Used as intraarticular injection DEXAMETHASONE  Potent and highly selective, long acting  Marked HPA suppression  Inflammatory and allergic condition  Shock, cerebral edema. 34
  • 35. FLUDROCORTISONE  Potent mineralocorticoid having some GC activity  Replacement therapy in Addison’s disease  Congenital adrenal hyperplasia  Idiopathic hypotension 35
  • 36. THERAPEUTIC USES  Physiologic doses of Corticosteroids are used for replacement therapy  Supraphysiologic doses are used for their antiinflammatory effects  immunosuppressive effects In organ transplant patients and those with autoimmune disorders 36
  • 37. REPLACEMENT THERAPY Adrenal insufficiency – acute/chronic  Abrupt withdrawal of steroid therapy  Chronic infections – Tuberculosis  Autoimmune adrenal disease  Surgery, Hemorrhage and AIDS Congenital adrenal hyperplasia  Congenital disorder due to deficiency of 21-hydroxylse enzyme – no cortisol but ACTH – increased androgen production 37
  • 38. REPLACEMENT THERAPY ACUTE ADRENAL INSUFFICIENCY  IV Hydrocortisone/ Dexamethasone bolus f/b infusion  Monitor CVP  Short term infusion of dopamine CHRONIC ADRENAL INSUFFICIENCY  Hydrocortisone orally  If needed ad fludrocortisone 38
  • 39. REPLACEMENT THERAPY CONGENITAL ADRENAL HYPERPLASIA  Hydrocortisone 0.6 mg/kg in divided doses  Fludrocortisone 10-20 µg/kg if salt wasting persist 39
  • 40. MUST KNOW  Biosynthesis and Regulation of Corticosteroids  Mechanism of action of Corticosteroids  Name of commonly used Glucocorticoids  Anti-inflammatory and immunosuppressive actions of Glucocorticoids 40
  • 41. 3/09/13 99.16,100,34.62,56,39,38,33,78,94,71,17,29,44,37,81,92,48,10,66,9 ,70,73,21,75,58,53,60,27,20,19,14,22,88,52,89,5,2,86,68,69,28,45, 8,13,26,41,32,54,82,74,98,11,3,47,93,55,91,63,49,30,15,95,64,96,77 ,18,101,76 06/09/13 38,99,16,100,52,40,35,71,78,94,89,86,5,69,2,28,53,58,75,21,70,33, 73,60,92,66,9,37,27,20,19,88,22,14,34,56,62,13,45,85,7,36,49,46,1 1,98,54,50,59,82,3,18,47,30,51,15,23,63,57,61,91,12,93,101,96,95,6 7 41
  • 42. CORTICOSTEROIDS Dr Mayur Chaudhari Assistant Professor Department of Pharmacology Government Medical College, Surat
  • 43. OBJECTIVES  Pharmacotherapy  Adverse Effects  Contraindications 43
  • 44. GENERAL PRINCIPLES  Single dose is not harmful  Short Courses  Long term use – Hazardous  Initial Dose – According to severity  No abrupt withdrawal  Local Therapy 44
  • 45. Pharmacotherapy 45
  • 46. ARTHRITIDES  Rheumatoid Arthritis  Osteoarthritis  Rheumatic fever  Gout 46
  • 47. COLLAGEN DISEASES  Systemic Lupus Erythematous  Nephrotic Syndrome  Glomerulonephritis 47
  • 48. SEVERE ALLERGIC REACTIONS  Anaphylaxis  Angioneurotic edema  Urticaria  Serum Sickness  Allergic conjunctivitis  Allergic Rhinitis 48
  • 49. AUTOIMMUNE DISEASES  Hemolytic anemia  Idiopathic thrombocytopenic purpura  Active chronic hepatitis 49
  • 50. BRONCHIAL ASTHMA  Status asthmaticus  Acute asthma exacerbation  Severe chronic asthma 50
  • 51. LUNG DISEASES  Aspiration pneumonia  Pulmonary edema  Lung maturation in fetus 51
  • 52. INFECTION  Severe tuberculosis  Lepra reaction  Bacterial meningitis  Pneumocystis carinii pneumonia 52
  • 53. EYE DISEASES  Allergic conjunctivitis  Iritis  Iridocyclitis  Keratitis 53
  • 54. SKIN DISEASES  Eczema  Pemphigus vulgaris  Exfoliative dermatitis  Steven Johnson Syndrome 54
  • 55. INTESTINAL DISEASES  Ulcerative colitis  Crohn’s Disease  Coeliac Disease 55
  • 56.  CEREBRAL OEDEMA  NEUROCYSTICERCOSIS  MALIGNANCIES  ORGAN TRANSPLANT  SKIN ALLOGRAFT 56
  • 57.  SEPTIC SHOCK  THYROID STORM  PITUITARY ADRENAL AXIS FUNCTION 57
  • 58. ADVERSE EFFECTS 58
  • 59. MINERALOCORTICOID  Na+ and water retention  Edema  Hypokalemic alkalosis  Progressive rise in BP 59
  • 60. GLUCOCORTICOID  Cushing’s habitus  Fragile skin, Purple Striae  Hyperglycemia  Muscular Weakness  Delayed healing 60
  • 61.  Susceptibility to infection  Peptic Ulceration  Osteoporosis  Posterior Sub capsular cataract  Glaucoma  Growth Retardation  Foetal abnormality 61
  • 62.  Psychiatric Disturbances  HPA Axis Suppression 62
  • 63. CONTRAINDICATIONS  Peptic ulcer  Diabetes mellitus  Hypertension  Viral and fungal infections  Tuberculosis 63
  • 64. CONTRAINDICATIONS  Osteoporosis  Herpes simplex keratitis  Psychosis  Epilepsy  Congestive heart failure  Renal Failure 64
  • 65. SUMMARY  Guidelines for use of glucocorticoids  Pharmacotherapy  Adverse effects  Contraindications 65

×