Adrenal%20steroids

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Adrenal steroids

• Dr Sanjeewani Fonseka
• Department of Pharmacology

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Objectives

• Recall the physiological effect of adrenocortical
  steroids
• Describe the anti- inflammatory and
  immunosuppressive effects of glucocorticoids
• Compare the relative potency, glucocorticoid/miner
  alocorticoid 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

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• Endogenous Glucocorticoids
• Hydrocortisone
• Corticosterone

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Corticosteroids are Gene-Active
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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

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Action of glucocorticoids

• Metabolic
• Anti-inflammatory
• Immunosuppressive

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Actions

1. Stomach
2. Blood
3. Anti-inflammatory
4. Immunosuppressant
5. Growth and Cell Division
6. Calcium metabolism

1. Carbohydrate
2. Protein
3. Lipid
4. Electrolyte and H2O
5. CVS
6. Skeletal Muscle
7. CNS

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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
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protein metabolism

• Negative nitrogen balance
• Decreased protein synthesis
• Increased protein breakdown

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Skeletal Muscles
Needed for maintaining the normal function of
Skeletal muscle

• Addison's disease weakness and fatigue is due to
  
• Prolonged use

inadequacy of circulatory system
Steroid myopathy
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Lipid metabolism

• Redistribution of Fat

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Electrolyte and water balance

• Act on DT and CD of kidney
• Na reabsorption
• Urinary excretion of K and H

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CNS

• Direct
• Mood
• Behavior
• Brain excitability
• Indirect
• maintain glucose, circulation and electrolyte
  balance

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Stomach

• Acid and pepsin secretion
• immune response to H.Pylori

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Blood

• RBC Hb and RBC content
• (erythrophagocytosis)
• WBC Lymphocytes, eosinophils, monocytes,
  basophils
• Polymorphonucleocytes

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Actions on inflammatory cells

• Recruitment of N, monocytes, macrophage into
  affected area
• Action of fibroblasts
• T helper action
• Osteoblast
• osteoclast

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Inflammatory mediators

• Reduced cytokines
• Reduced complement
• Reduced histamine

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Anti-inflammatory actions of corticosteroids
Corticosteroid inhibitory effect
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Growth and Cell division

• Inhibit cell division or synthesis of DNA
• Delay the process of healing
• Retard the growth of children

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Calcium metabolism

• Intestinal absorption
• Renal excretion
• Excessive loss of calcium from bones (e.g.,
  vertebrae, ribs, etc)
• Osteoporosis

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Pharmacological Actions

• synthetic glucocorticoids are used because they
  have a higher affinity for the receptor
• have little or no salt-retaining properties.

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Clinical uses

• Replacement therapy
• Immunosuppressive / anti-inflammatory therapy
• Neoplastic disease

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Types of Steroids

• Replacement Therapy
• glucocorticoid (hydrocortisone)
• mineralocorticoid (fludrocortisone)

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• Anti-inflammatory Therapy
• Short acting hydrocortisone
• Intermediate acting prednisolone,
  methylprednisolone, triamcinolone
• Long acting dexamethasone

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Preparations Preparations Preparations Preparations
Drug Anti-inflam. Salt retaining Topical
Cortisol 1 1.0 1
Cortisone 0.8 0.8 0
Prednisone 4 0.8 0
Prednisolone 5 0.3 4
Methylpredni- solone 5 0 5
Intermediate acting Intermediate acting Intermediate acting Intermediate acting
Triamcinolone 5 0 5
Paramethasone 10 0 -
Fluprednisolone 15 0 7
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Preparations Preparations Preparations Preparations
Drug Anti-inflam. Salt retaining Topical
Long acting Long acting Long acting Long acting
Betamethasone 25-40 0 10
Dexamethasone 30 0 10
Mineralocorticoids Mineralocorticoids Mineralocorticoids Mineralocorticoids
Fludrocortisone 10 250 10
DOCA 0 20 0
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Side effects

• Not seen in replacement therapy
• Seen if used for anti-inflammatory property
• Excess of physiological actions

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Iatrogenic Cushings syndrome
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Adverse effects (long term)

• Glucose intolerance
• Acne
• Hypertension, edema
• Susceptibility to infection (TB, fungal)
• Myopathy
• Behavior mood changes

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Adverse effects (long term)

• Avascular necrosis of bone
• Cataract
• Peptic ulcer
• Skin atrophy, delayed wound healing
• Growth retardation (children)
• Suppression of HPA axis

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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

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• Read
• Monitoring while on steroids
• Pregnancy and steroids
• Infections and long term steroid
• Surgery and steroids

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Summary
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long term steroids

• Monitor BP, electrolyte and blood sugar
• Advise moderate exercise
• Bone protection measures
• Gastric protection if needed

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• Give morning dose
• Every other day
• Minimum effective dose
• Steroid sparing agents

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• Read
• Mineralocorticoids action, side effects,
  clinical uses