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 anti-inflammatory gene targets increased by corticosteroids.

Increased expression of anti-inflammatory genes:

Answer 3

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 4

Name a clinically used corticosteroid with equal glucocorticoid and mineralocorticoid effects

Answer 4

Hydrocortisone (cortisol)

Question 5

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

Answer 5

Methylprednisolone, Triamcinolone, Betamethasone, Dexamethasone

Question 6

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

Answer 6

Betamethasone, Dexamethasone

Question 7

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

Answer 7

Betamethasone

Question 8

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

Answer 8

Hydrocortisone (cortisol)

Question 9

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

Answer 9

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 10

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

Answer 10

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

Question 11

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

Answer 11

Immunosuppression leading to opportunistic infections:
Bacterial (TB), Viral(Herpes&CMV), Fungal (Canadidal, Asperigilles & Crytococcal), Parasitic (Toxoplasmosis)

Question 12

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

Answer 12

• Posterior Subcapsular Lens Cataract
• Glaucoma

Question 13

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

Answer 13

Nervous System
* Euphoria, depression, psychosis

Question 14

List principles of corticosteroid therapy

Answer 14

• 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: chest X-Ray, tuberculosis, diabetes mellitus, peptic ulcer disease, osteoporosis, and mental disorder

Question 15

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

Answer 15

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)