Adrenal steroids
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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


Adrenal steroids

Endogenous Glucocorticoids

Hydrocortisone

Corticosterone


Adrenal steroids

Corticosteroids are Gene-Active


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


Adrenal steroids

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


Adrenal steroids

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+


Adrenal steroids

CNS

  • Direct

    • Mood

    • Behavior

    • Brain excitability

  • Indirect

    • maintain glucose, circulation and electrolyte balance


Adrenal steroids

Stomach

  • Acid and pepsin secretion

  • immune response to H.Pylori


Adrenal steroids

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


Adrenal steroids

Anti-inflammatory actions of corticosteroids

Corticosteroid inhibitory effect


Adrenal steroids

Growth and Cell division

  • Inhibit cell division or synthesis of DNA

  • Delay the process of healing

  • Retard the growth of children


Adrenal steroids

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)


Adrenal steroids

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


Iatrogenic cushing s syndrome

Iatrogenic Cushing’s syndrome


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


Adrenal steroids

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Monitoring while on steroids

Pregnancy and steroids

Infections and long term steroid

Surgery and steroids


Summary

Summary


Long term steroids

long term steroids

  • Monitor BP, electrolyte and blood sugar

  • Advise moderate exercise

  • Bone protection measures

  • Gastric protection if needed


Adrenal steroids

  • Give morning dose

  • Every other day

  • Minimum effective dose

  • Steroid sparing agents


Adrenal steroids

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  • Mineralocorticoids – action, side effects, clinical uses


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