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.
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
8. REGULATION
Synthesized and Released
under influence of ACTH
and Pituitary.
Regulated by CRH from
hypothalamus
and
by
feedback levels of blood
concentrations
8
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
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
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
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
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
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