Glucocorticoids Pharmacology

Question 1

MA of Glucocorticoids

Answer 1

Inhibit gene transcription of COX-2 -> reduction of prostaglandin synthesis

Bind to cytoplasmic glucocorticosteroid receptor -> the complex inhibits transcription of many pro-inflammatory proteins

Reduces T-cell proliferation and
migration of inflammatory cells -> resulting in
impaired cell mediated immunity

Question 2

Glucocorticoid effects

Answer 2

Anti-inflammatory
(redness, swelling, pain and heat)
Anti-allergic
Antirheumatic

Question 3

Metabolic effects of glucocorticoids

Answer 3

Increased gluconeogenesis caused by:
inhibition of peripheral protein synthesis so that amino acids are available for glucose synthesis,

Decrease in glucose transport across membranes
reducing peripheral utilisation of glucose

Increased fatty acid release from fatty tissue and increased body fat deposited on face and trunk (moon faces, truncal obesity, buffalo hump)

New onset diabetes

Antigrowth hormone

Adrenal insufficiency

Question 4

Metabolic effects of mineralocorticoids

Answer 4

Mimic aldosterone effects on the distal nephron :
Sodium retention
Potassium loss

Conn’s syndrome

Mineralocorticoid excess disease (aldosterone antagonists used to treat it –Spironolactone
and Eplerenone)

Question 5

Hydrocortisone

Answer 5

Predominantly glucocorticoid with significant
mineralocorticoid activity

Absorption from variable , presystemic elimination

Metabolised in the liver -> decreased BA

Plasma half life 90mins (biological half life longer)

Question 6

Prednisolone

Answer 6

Similar to hydrocortisone

Anti-inflammatory -four times more potent

Less active as a mineralocorticoid

Question 7

Dexamethosone

Betamethasone

Answer 7

Powerful anti-inflammatory

No mineralocorticoid
effects

Question 8

Mineralocorticoid examples

Answer 8

Aldosterone

Fludrocortisone

Question 9

Aldosterone

Answer 9

1000 times more potent than hydrocortisone as mineralocorticoid

Acts on distal nephron – sodium and water retention, potassium loss

Question 10

Fludrocortisone

Answer 10

500 times more potent than hydrocortisone as mineralocorticoid

Used as replacement therapy in patients with
adrenocortical insufficiency

Administered orally, undergoes presystemic elimination

Question 11

Clinical Uses 1

Answer 11

Treatment of respiratory diseases: 
Asthma, Hayfever
Sarcoidosis
Extrinsic allergic alveolitis
Fibosing alveolitis

Treatment of rheumatic and collagen disease:
Rheumatoid Arthritis 
Polymyalgia rheumatica
Systemic Lupus Erythromatosis
Dermatomyositis

Question 12

Clinical Uses 2

Answer 12

Treatment of skin disorders:
Eczema, psoriasis

Organ transplantation

Treatment of shock

Treatment of liver disease

Treatment of GIT disease:
Ulcerative colitis, Crohn’s

Treatment of nephrotic syndrome

Treatment of hypercalcaemia (sarcoidosis)

Treatment of brain oedema (inflammatory origin)

Replacement therapy in Addison’s disease

Treatment of congenital adrenal hyperplasia

Question 13

Unwanted effects

Answer 13

Cushingoid physical appearance

Impaired resistance to infection

Delayed wound healing

Salt and water retention

Hypokalaemia

Hypertension

Hyperglycaemia

Osteoporosis

Peptic ulcer disease

Mental changes: anxiety, insomnia,elation, depression,
psychosis