Corticosteroids

Question 1

Mechanism of action (glucocorticoid effects)?

Answer 1

Glucocorticoid effects, they bind to their cytosolic receptors, translocate to the nucleus, bind to glucocorticoid response-elements which regulate gene expression. Corticosteroids modify the immune response by upregularting anti-inflammatory genes and downregulating pro-inflammatory genes.

Question 2

Mechanism of action (metabolic effects)?

Answer 2

Metabolic effects include increased gluconeogenesis, from increased circulating amino-acids and fatty acids released by catabolism.

Question 3

Mechanism of action (mineralocorticoid effects)?

Answer 3

Mineralocorticoid effects due to activation of Na/K pump, promoting retention of water and Na in opposition to K excretion.

Question 4

Indications ?

Answer 4

Allergic or Inflammatory disorders
Suppression of autoimmune diseases
Cancer; either as part of the chemotherapy or to reduce tumor-assisted swelling (oedemas)
Hormone replacement in Adrenal insufficiency or Hypopituitarism

Question 5

Important AE ?

Answer 5

Immunosuppression, diabetes, osteoporosis, muscle weakness, skin thinning, mood and behavioural changes, insomnia, confusion, psychosis and suicidal thoughts. Hypertension, hypokaliemia and oedema.

Question 6

Important cautions ?

Answer 6

As they suppress ACTH secretion = normal stimulus adrenal cortisol production. In prolonged treatments, this causes adrenal atrophy, preventing endogenous cortisol. If they withdrawn suddenly, acute Addisonian crisis (adrenal insufficiency) with cardiovascular collapse may occur. Slow withdrawal is required for recovery of the adrenal function.

Question 7

Important interactions ?

Answer 7

With NSAIDs, they increase the risk of peptic ulceration and gastrointestinal bleeding.
With b2 agonists, loop diuretics and thiazide diuretics, they enhance hypokaliemia.
With enzymatic inducers, their efficacy is reduced (phenytoin, carbamazepin, rifampicin)

Question 8

Corticosteroids, name them ?

Answer 8

Prednisolone
Hydrocortisone
Dexamethasone

Question 9

Which is the most potent ?

Answer 9

Dexamethasone

20 mg Hydro = 5 mg of Predni = 750 ug of dexa

Question 10

How are corticosteroids prescribed ?

Answer 10

Orally, IV or IM.

• In acute asthma, Predni in doses of about 40mg orally daily.
• In cerebral oedema due to cancer, Dexa as high as 8mg twice orally or by IV.
• Where oral admin is inappropriate, IBD or anaphylaxis, IV Hydro can be used.
• In inflammatory arthritis, Predni co-admin with steroid-sparing agents (Azathioprine, Methotrexate)
• Consider use of biphosphonates/PPI to reduce steroids side effects.

Question 11

Azathioprine ?

Answer 11

An immunosuppressive medication, used in rheumatoid arthritis, granulomatosis with polyangitis, Crohn’s disease, ulcerative colitis, and in kidney transplants. Per os/IV

Question 12

Methothrexate ?

Answer 12

Antimetabolite, antagoniste de l’acide folique.

Question 13

Steroid-sparing agents ?

Answer 13

or Steroid avoidance treatment, immunosuppressants with relatively better risk/benefits ratio than what corticosteroids offer.

Question 14

Biphosphonates ?

Answer 14

Class of drugs that prevent the loss of bone density (slowing down osteoclasts), used to treat osteoporosis and similar diseases. With two phosphonate PO(OH)2

Question 15

How are corticosteroids able to reduce brain oedema ?

Answer 15

by reducing permeability of the brain blood barrier and possibly inhibiting active sodium transport.