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

GlucocorticoidsKinetics:• 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

2. Protein

3. Lipid

4. Electrolyte and

H2O

5. CVS

6. Skeletal Muscle

7. CNS

8. Stomach

9. Blood

10. Anti-inflammatory

11. Immunosuppressant

12.Growth and Cell

Division

13. Calcium 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

Negative nitrogen balance

• Decreased protein synthesis

• Increased protein breakdown

Addison's disease: weakness and fatigue is due to

Prolonged use:

Skeletal Muscles

Needed for maintaining the normal function of Skeletal muscle

inadequacy of circulatory system

Steroid myopathy

• Redistribution of Fat

Lipid metabolism

Electrolyte and water balance

Act on DT and CD of kidney

– Na+ reabsorption

– Urinary excretion of K+ and H+

• Direct– Mood– Behavior– Brain excitability

• Indirect– maintain glucose, circulation and electrolyte

balance

CNS

– Acid and pepsin secretion

– immune response to H.Pylori

Stomach

RBC: Hb and RBC content

(erythrophagocytosis)

WBC: Lymphocytes, eosinophils, monocytes, basophils

Polymorphonucleocytes

Blood

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

• Inhibit cell division or synthesis of DNA

• Delay the process of healing

• Retard the growth of children

Growth and Cell division

• Intestinal absorption

• Renal excretion

• Excessive loss of calcium from bones (e.g., vertebrae, ribs, etc)

• Osteoporosis

Calcium metabolism

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

PreparationsDrug Anti-inflam. Salt retaining Topical

Cortisol 1 1.0 1Cortisone 0.8 0.8 0Prednisone 4 0.8 0Prednisolone 5 0.3 4Methylpredni- solone

5 0 5

Intermediate actingTriamcinolone 5 0 5Paramethasone 10 0 -Fluprednisolone 15 0 7

PreparationsDrug Anti-inflam. Salt retaining Topical

Long actingBetamethasone 25-40 0 10Dexamethasone 30 0 10

MineralocorticoidsFludrocortisone 10 250 10DOCA 0 20 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