ADRENOCORTICOSTEROIDS

INTRODUCTION

•      PRODUCED IN ADRENAL CORTEX

•      REGULATED BY ACTH

•      SYNTHESIZED FROM CHOLESTEROL

•      MINERALOCORTICOID

–   Electrolyte homeostasis (e.g. aldosterone)

•      GLUCOCORTICOID

–   Carbohydrate, fat, & protein metabolism

–   example:  cortisol

DISEASE STATES

•      Cushing’s Disease

–   High output of adrenocorticosteroids

–   Hypertension

–   Fat Redistribution

•      Addison’s Disease

–   Low production of adrenocorticosteroids

–   Requires therapy with mineralocorticoids and glucocorticoids

PHARMACOLOGY

•      CARBOHYDRATE METABOLISM

–   Protection under physical stress

–   Protect glucose dependent brain function

•   gluconeogenesis

•   reduce peripheral glucose utilization

•   insensitivity to insulin

PHARMACOLOGY

•      LIPID METABOLISM

–   Lipogenesis and Lipolysis

–   Fat redistribution: buffalo hump, moon face

•      ELECTROLYTE BALANCE

–   Sodium and Water Retention

–   Increased Blood Pressure

–   Potassium Loss

–   Addison’s: opposite effect-hyperkalemia and circulatory collapse

PHARMACOLOGY - CNS

•      Corticosteroids

–   Depression

•      Addison’s Disease

–   Apathy

–   Psychosis

PHARMACOLOGY

•      HEMATOLOGIC

–   Decrease WBC (specifically lymphocytes)

•      DECREASE IMMUNE RESPONSE

•      ANTI INFLAMMATORY RESPONSE

•      RETARD GROWTH INCHILDREN (ß bone growth)

CORTICOSTEROID WITHDRAWAL

•      Acute adrenal insufficiency

–   fever

–   myalgia

–   arthralgia

–   malaise

•      Avoid by gradual withdrawal of therapy

CONSEQUENCES OF PROLONGED THERAPY

•      Adrenal Suppression

•      Fluid and Electrolyte Imbalance

•      Peptic Ulceration

•      Depression

•      Cataracts

•      Osteoporosis

CLINICAL USE

•      Adrenal Insufficiency

–   administer both mineralo and gluco-corticoids

•      Rheumatoid Arthritis

•      Allergic Disorder - not anaphylactic

•      Asthma

•      Ocular Disease - avoid if viral infection

•      Skin Disorder

•      Lymphocytic leukemia

Other Agents

•      Aminoglutethimide

–   Decreases production of sterol including sex hormones

•      Mitotane

–   Adrenocorticolytic