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
Glucocorticoids
Kinetics:
•
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
8. Stomach
2. Protein
9. Blood
3. Lipid
10. Anti-inflammatory
4. Electrolyte and
H2O
11. Immunosuppressant
5. CVS
12.Growth and Cell
Division
6. Skeletal Muscle
13. Calcium metabolism
7. CNS
Carbohydrate metabolism
• Gluconeogenesis
– Peripheral actions (mobilize
– Hepatic actions
glucose and glycogen)
• 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
Skeletal Muscles
Needed for maintaining the normal function of Skeletal
muscle
Addison's disease: weakness and fatigue is
due to
inadequacy of circulatory system
Prolonged use: Steroid myopathy
Lipid metabolism
• Redistribution of Fat
Electrolyte and water balance
Act on DT and CD of kidney
–
Na+ reabsorption
– Urinary excretion of K+ and H+
CNS
• Direct
– Mood
– Behavior
– Brain excitability
• Indirect
– maintain glucose, circulation and electrolyte
balance
Stomach
– Acid and pepsin secretion
– immune response to H.Pylori
Blood
RBC: Hb and RBC content
(erythrophagocytosis)
WBC: Lymphocytes, eosinophils,
monocytes, basophils
Polymorphonucleocytes
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
Growth and Cell division
• Inhibit cell division
or synthesis of DNA
• Delay the process of
healing
• Retard the growth of
children
Calcium metabolism
•
Intestinal absorption
•
Renal excretion
•
Excessive loss of calcium from bones
(e.g., vertebrae, ribs, etc)
• Osteoporosis
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
Preparations
Drug
Cortisol
Anti-inflam.
Salt retaining
Topical
1
1.0
1
0.8
0.8
0
Prednisone
4
0.8
0
Prednisolone
5
0.3
4
Methylprednisolone
5
0
5
5
0
5
Paramethasone
10
0
-
Fluprednisolone
15
0
7
Cortisone
Intermediate acting
Triamcinolone
Preparations
Drug
Anti-inflam.
Salt retaining
Topical
Long acting
Betamethasone
25-40
Dexamethasone
30
Mineralocorticoids
Fludrocortisone
10
DOCA
0
0
0
10
10
250
20
10
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