adrenal steroids dr sanjeewani fonseka department of pharmacology
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Adrenal steroids
Dr Sanjeewani Fonseka
Department of Pharmacology
Objectives• Recall the physiological effect of adrenocortical steroids
• Describe the anti- inflammatory and immunosuppressive effects of glucocorticoids
• Compare the relative potency, glucocorticoid/mineralocorticoid activity and duration of action of commonly available steroid drugs
• List clinical uses and adverse effects of glucocorticoid drugs
• Explain the principles underling replacement therapy in adrenocortical insufficiency
• Describe the precautions that can be taken to minimize the adverse effects of long-term steroid therapy
Endogenous Glucocorticoids
Hydrocortisone
Corticosterone
Corticosteroids are Gene-Active
GlucocorticoidsKinetics:• Well absorbed orally
• Bound to corticosteroid-binding globulin and albumin
• Distributed all over the body & passes the BBB
• In the liver, cortisol is reversibly converted to cortisone & conjugated with glucuronic & sulfuric acid
• Excreted in urine as 17-hydroxy corticosteroids
Action of glucocorticoids
• Metabolic
• Anti-inflammatory
• Immunosuppressive
Actions
1. Carbohydrate
2. Protein
3. Lipid
4. Electrolyte and
H2O
5. CVS
6. Skeletal Muscle
7. CNS
8. Stomach
9. Blood
10. Anti-inflammatory
11. Immunosuppressant
12.Growth and Cell
Division
13. Calcium metabolism
Carbohydrate metabolism
• Gluconeogenesis– Peripheral actions (mobilize glucose and glycogen)
– Hepatic actions
• Peripheral utilization of glucose
• Glycogen deposition in liver(activation of hepatic glycogen synthase)
hyperglycemia
protein metabolism
Negative nitrogen balance
• Decreased protein synthesis
• Increased protein breakdown
Addison's disease: weakness and fatigue is due to
Prolonged use:
Skeletal Muscles
Needed for maintaining the normal function of Skeletal muscle
inadequacy of circulatory system
Steroid myopathy
• Redistribution of Fat
Lipid metabolism
Electrolyte and water balance
Act on DT and CD of kidney
– Na+ reabsorption
– Urinary excretion of K+ and H+
• Direct– Mood– Behavior– Brain excitability
• Indirect– maintain glucose, circulation and electrolyte
balance
CNS
– Acid and pepsin secretion
– immune response to H.Pylori
Stomach
RBC: Hb and RBC content
(erythrophagocytosis)
WBC: Lymphocytes, eosinophils, monocytes, basophils
Polymorphonucleocytes
Blood
Actions on inflammatory cells
• Recruitment of N, monocytes, macrophage into affected area
• Action of fibroblasts
• T helper action
• Osteoblast
• osteoclast
Inflammatory mediators
• Reduced cytokines
• Reduced complement
• Reduced histamine
Anti-inflammatory actions of corticosteroids
Corticosteroid inhibitory effect
• Inhibit cell division or synthesis of DNA
• Delay the process of healing
• Retard the growth of children
Growth and Cell division
• Intestinal absorption
• Renal excretion
• Excessive loss of calcium from bones (e.g., vertebrae, ribs, etc)
• Osteoporosis
Calcium metabolism
Pharmacological Actions
• synthetic glucocorticoids are used because they have a higher affinity for the receptor
• have little or no salt-retaining properties.
Clinical uses
• Replacement therapy
• Immunosuppressive / anti-inflammatory therapy
• Neoplastic disease
Types of Steroids
Replacement Therapy
• glucocorticoid (hydrocortisone)
• mineralocorticoid (fludrocortisone)
Anti-inflammatory Therapy
• Short acting: hydrocortisone
• Intermediate acting: prednisolone, methylprednisolone, triamcinolone
• Long acting: dexamethasone
PreparationsDrug Anti-inflam. Salt retaining Topical
Cortisol 1 1.0 1Cortisone 0.8 0.8 0Prednisone 4 0.8 0Prednisolone 5 0.3 4Methylpredni- solone
5 0 5
Intermediate actingTriamcinolone 5 0 5Paramethasone 10 0 -Fluprednisolone 15 0 7
PreparationsDrug Anti-inflam. Salt retaining Topical
Long actingBetamethasone 25-40 0 10Dexamethasone 30 0 10
MineralocorticoidsFludrocortisone 10 250 10DOCA 0 20 0
Side effects
• Not seen in replacement therapy
• Seen if used for anti-inflammatory property
• Excess of physiological actions
Iatrogenic Cushing’s syndrome
Adverse effects (long term)
• Glucose intolerance
• Acne
• Hypertension, edema
• Susceptibility to infection (TB, fungal)
• Myopathy
• Behavior & mood changes
Adverse effects (long term)
• Avascular necrosis of bone
• Cataract
• Peptic ulcer
• Skin atrophy, delayed wound healing
• Growth retardation (children)
• Suppression of HPA axis
Drug interactions
• Estrogens - decrease prednisone clearance
• Phenobarbital, phenytoin, and rifampicin - increase metabolism of glucocorticoids
• May cause digitalis toxicity secondary to hypokalemia
• Monitor for hypokalemia with co-administration of diuretics
Read
Monitoring while on steroids
Pregnancy and steroids
Infections and long term steroid
Surgery and steroids
Summary
long term steroids
• Monitor BP, electrolyte and blood sugar
• Advise moderate exercise
• Bone protection measures
• Gastric protection if needed
• Give morning dose
• Every other day
• Minimum effective dose
• Steroid sparing agents
Read
• Mineralocorticoids – action, side effects, clinical uses