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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

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adrenal steroids

Adrenal steroids

Dr SanjeewaniFonseka

Department of Pharmacology

objectives
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
slide5
Endogenous Glucocorticoids

Hydrocortisone

Corticosterone

glucocorticoids
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
Action of glucocorticoids
  • Metabolic
  • Anti-inflammatory
  • Immunosuppressive
actions
Actions
  • Carbohydrate
  • Protein
  • Lipid
  • Electrolyte and H2O
  • CVS
  • Skeletal Muscle
  • CNS
  • Stomach
  • Blood
  • Anti-inflammatory
  • Immunosuppressant
  • Growth and Cell Division
  • Calcium metabolism
carbohydrate 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
protein metabolism

Negative nitrogen balance

  • Decreased protein synthesis
  • Increased protein breakdown
slide15
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

slide16
Lipid metabolism
  • Redistribution of Fat
electrolyte and water balance
Electrolyte and water balance

Act on DT and CD of kidney

  • Na+ reabsorption
  • Urinary excretion of K+ and H+
slide18
CNS
  • Direct
    • Mood
    • Behavior
    • Brain excitability
  • Indirect
    • maintain glucose, circulation and electrolyte balance
slide19
Stomach
  • Acid and pepsin secretion
  • immune response to H.Pylori
slide20
Blood

RBC: Hb and RBC content

(erythrophagocytosis)

WBC: Lymphocytes, eosinophils, monocytes, basophils

Polymorphonucleocytes

actions on inflammatory cells
Actions on inflammatory cells
  • Recruitment of N, monocytes, macrophage into affected area
  • Action of fibroblasts
  • T helper action
  • Osteoblast
  • osteoclast
inflammatory mediators
Inflammatory mediators
  • Reduced cytokines
  • Reduced complement
  • Reduced histamine
slide23
Anti-inflammatory actions of corticosteroids

Corticosteroid inhibitory effect

slide24
Growth and Cell division
  • Inhibit cell division or synthesis of DNA
  • Delay the process of healing
  • Retard the growth of children
slide25
Calcium metabolism
  • Intestinal absorption
  • Renal excretion
  • Excessive loss of calcium from bones (e.g., vertebrae, ribs, etc)
  • Osteoporosis
pharmacological actions
Pharmacological Actions
  • synthetic glucocorticoids are used because they have a higher affinity for the receptor
  • have little or no salt-retaining properties.
clinical uses
Clinical uses
  • Replacement therapy
  • Immunosuppressive / anti-inflammatory therapy
  • Neoplastic disease
types of steroids
Types of Steroids

Replacement Therapy

  • glucocorticoid (hydrocortisone)
  • mineralocorticoid (fludrocortisone)
slide29
Anti-inflammatory Therapy
  • Short acting: hydrocortisone
  • Intermediate acting: prednisolone, methylprednisolone, triamcinolone
  • Long acting: dexamethasone
side effects
Side effects
  • Not seen in replacement therapy
  • Seen if used for anti-inflammatory property
  • Excess of physiological actions
adverse effects long term
Adverse effects (long term)
  • Glucose intolerance
  • Acne
  • Hypertension, edema
  • Susceptibility to infection (TB, fungal)
  • Myopathy
  • Behavior & mood changes
adverse effects long term1
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
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
slide41
Read

Monitoring while on steroids

Pregnancy and steroids

Infections and long term steroid

Surgery and steroids

long term steroids
long term steroids
  • Monitor BP, electrolyte and blood sugar
  • Advise moderate exercise
  • Bone protection measures
  • Gastric protection if needed
slide45
Give morning dose
  • Every other day
  • Minimum effective dose
  • Steroid sparing agents
slide47
Read
  • Mineralocorticoids – action, side effects, clinical uses
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