Steroids

Question 1

Where in the body do steroids work?

Answer 1

Cell membranes and cell signalling- anti inflammatory agents

Question 2

What are natural steroids found in the body?

Answer 2

Cholesterol testosterone and oestrogen

Question 3

What drugs are examples of steroids?

Answer 3

*dexamethasone, betamethasone, prednisolone, hydrocortisone, beclametasone

Question 4

What is the general structure of a steroid?

Answer 4

• 3 cyclohexane rings
• 1 cyclopentane ring
  Variation due to different functional groups attached

Question 5

What is the role of cholesterol in the body?

Answer 5

*Membrane fluidity and permeability- Increased cholesterol=decreased permeability due to increased packing density
*precursor for biosynthesis of cellular constituents (vit D and hormones)

Question 6

What is steroidgenesis?

Answer 6

Biological process where steroid HORMONES are generated from cholesterol
Cleaved and modified by CYP450

Question 7

What is the function of steroid hormones in the body?

Answer 7

CORTICOSTEROIDS
*produced in adrenal cortex
*regulate immune function, stress response and metabolism
Eg cortisol, aldosterone

SEX STEROIDS
*produced in overuse, testes, adrenal gland
Eg testosterone, est radios and progesterone

Question 8

How do steroids work as anti inflammatorys?

Answer 8

Reduce production of inflammatory mediators- cytokines

Question 9

How do steroids work as immunosuppressive drugs?

Answer 9

Alter immune cell functioning

Question 10

What steroids are used to treat asthma?

Answer 10

INHALED
*beclometasone diproprionate
*fluticasone proprionate
*budesonide
ORAL
*prednisolone

Question 11

How does dexamethasone work as an anti inflammatory?

Answer 11

*reduces vasodilation and permeability of vessels
*regulates gene expression
*dampens immune cell activation

Question 12

Why does dexamethasone work in severe cases of Covid-19 ?

Answer 12

*will need mechanical ventilation- up-regulates ACE2 expression allowing virus entry into cells
*dexamethasone blocks pathway avoiding increased ACE2 expression and thus reduces viral entry

Question 13

What is the MOA of steroids?

Answer 13

*glucocorticoid + gluco receptor
*binding displaces chaperones (HSP90)
*steroid- receptor complex can form a dimer- enter nucleus
*1. Cause transcription/translation of IkB (binds to SRE on genes and acts as transcription factor)
-inhibits NFkB (a pro inflammatory to produce cytokines)
*2. Directly interact with NFkB (p50:p65) to suppress cytokine synthesis (eg TNF)
*3. Promote production of anti inflammatory cytokines such as IL-10
*4. Promote apoptosis of T cells and macrophages
-reduce B cell antibody production
-reduce expression of cell surface molecules important for T cell activation
*5. Increase transcription of lipocortins
-suppress COX expression
-reduced production of ecosanoids

Question 14

Where are most steroid inhalers excreted?

Answer 14

Faeces

Question 15

What is the main glucocorticoid secreted by adrenal cortex?

Answer 15

Hydrocortisone
(Used as emergency in asthma)