Corticosteroids

Question 1

List effects of corticosteroids in airway smooth muscle.

Answer 1

Corticosteroids have numerous actions including increased expression of beta-2 adrenoceptors and reduction of expression of cytokines.

Question 2

What is fludrocortisone?

Answer 2

Fludrocortisone is a mineralocorticoid synthetic analogue. Fludrocortisone is used to treat conditions in which the body does not produce enough of its own steroids, e.g., Addison’s disease, and salt-losing adrenogenital syndrome

Question 3

List at least FIVE examples of pro-inflammatory gene targets decreased by corticosteroids.

Answer 3

Reduced expression of pro-inflammatory genes:
Cytokines e.g., TNF‐α,IL‐1β, IL‐2,IL‐4,IL‐5,IL‐13,IL‐33,IFNγ
Chemokines e.g., RANTES,Eotaxin,MIP‐1α,MCP‐1
Inflammatory enzymes e.g., Cyclooxygenase‐2(COX‐2), 5‐Lipoxygenase (5‐LOX), Phospholipase A2 (PLA2)
Adhesion Molecules e.g., ICAM‐1, VCAM‐1, E‐Selectin
Receptors e.g., IL‐2R (αchain), T‐CellReceptor (βchain)

Question 4

List at least FIVE examples of anti-inflammatory gene targets increased by corticosteroids.

Answer 4

Increased expression of anti-inflammatory genes:
Annexin‐A1: A PLA2 inhibitor
β2‐adrenoceptor
IL‐1 Receptor Antagonist
IL‐1R2 (decoy receptor)
Neutral endopeptidase (NEP)
Endonucleases
IκB‐α (Inhibitor of NF‐κB)
MAPK Phosphatase‐1 (MKP‐1)

Question 5

Name a clinically used corticosteroid with equal glucocorticoid and mineralocorticoid effects

Answer 5

Hydrocortisone (cortisol)

Question 6

List at least THREE examples of corticosteroids with minimal or zero mineralocorticoid effect

Answer 6

Methylprednisolone, Triamcinolone, Betamethasone, Dexamethasone

Question 7

Name an example of a highly potent corticosteroids with a long duration of action (24 to 72 hours)

Answer 7

Betamethasone, Dexamethasone

Question 8

Name an example of a potent corticosteroid that is highly effective for topical application

Answer 8

Betamethasone

Question 9

Name an example of a corticosteroid with a short duration of action (8 to 12 hours)

Answer 9

Hydrocortisone (cortisol)

Question 10

List endocrine/metabolic/cardiovascular side effects of long-term treatment with corticosteroids

Answer 10

Endocrine‐Metabolic Effects:
• Hyperglycaemia (and increased risk of diabetes mellitus type II)
• Moonface, ‘buffalo hump’ & truncal obesity
• Muscle wasting
• Growth retardation (pediatric patients)
• Acne, hirsutism & menstrual disturbances
• Delayed wound healing
• Skin Thinning
• Na/fluid retention, oedema, hypertension, chronic heart failure

Question 11

List musculoskeletal system side effects of long-term treatment with corticosteroids

Answer 11

Musculoskeletal System
• Osteoporosis (trabecular bone)
• Aseptic necrosis of femoral head
• Myopathy (esp. dexamethasone/triamcinolone)

Question 12

List immune system side effects of long-term treatment with corticosteroids

Answer 12

Immunosuppression leading to opportunistic infections:

Bacterial (TB), Viral(Herpes&CMV), Fungal (Canadidal, Asperigilles & Crytococcal), Parasitic (Toxoplasmosis)

Question 13

List side effects in the eye of long-term treatment with corticosteroids

Answer 13

• Posterior Subcapsular Lens Cataract

* Glaucoma

Question 14

List central nervous system side effects of long-term treatment with corticosteroids

Answer 14

Nervous System

• Euphoria, depression, psychosis

Question 15

List principles of corticosteroid therapy

Answer 15

• Host response is the cause of symptoms
• Steroids are not usually curative
• Standard Choice: Shorter‐acting steroids with little salt‐retaining activity (e.g., prednisolone)
• At lowest possible dose(often still supra‐physiological) to achieve the desired effect
• Use alternate‐day therapy or pulse therapy, if possible
• Do not stop therapy abruptly (use gradual stepwise dose reduction)
• In prolonged therapy, check: ches tX‐Ray, tuberculosis, diabetes mellitus, peptic ulcer disease, osteoporosis, and mental disorder