Steroids Flashcards
What physiological roles do steroids Play in the body
Cell membranes and cell signalling
Anti inflammatory agents
Steroid structure
4 cycloalkane structure - 3 cyclohexane rings and 1 cyclopentane ring
Variation obtained by different functional groups attached to the 4-ring core and oxidation states of the rings
Biological role of cholesterol
Facilitates membrane fluidity
Controls membrane permeability
Synthetic precursor - important for the biosynthesis of many cellular constituents - Vitamin D and steroid hormones
Steroidgenesis
What is steroidgenesis
Biological process whereby steroid hormones are generated from cholesterol
Where are corticosteroids produced
Adrenal cortex
Where are sex steroids produced
Ovaries, testes, adrenal gland
What do corticosteroids do
Regulate immune function , stress response and metabolism
Examples of corticosteroid
GlucocorticoidS and mineralcorticoids
What do sex hormones do
Interact with estrogen or androgen receptors
Differentiate sex and support reproduction
Examples of sex hormones
Androgens (testosterone)
Oestrogens (estradiol)
Progestogens (progesterone)
What inflammatory mediator does steroids reduce the production of
Cytokines
What does dexamethasone treat
Asthma Allergies Cancer Colitis Arthritis
What does dexamethasone do
Anti inflammatory mechanism of action
Reduces vasodilation and permeability of vessels
Regulates gene expression
Dampens activation of immune cells
How does dexamethasone treat covid 19
Mechanical ventilation and stress up regulates ACE2 expression
Enables virus entry into cells
Dexamethasone and other steroids block this pathway , preventing increase in ACE2 expression
Steroid mechanism of action ( up to entering nucleus )
Steroid crosses plasma membrane and interacts with steroid receptor
Steroid binding to receptor displaces chaperone eg HSP90
Steroid receptor complexes can then form a dimer and enter the nucleus
What can the steroid receptor complex do once in nucleus
Cause transcription / translation of proteins such as IkB by binding to DNA and functioning as a transcription factor
Directly interact with NFkB (p50:p65) to suppress cytokine synthesis
What does iKb inhibit
NF-kB
What does NF-kB produce
Pro inflammatory proteins
What is a cytokine
Any of A number of substances such as interferons , interleukin and growth factors which are secreted by a certain no of cells of the immune system and have effects on other cells
Others ways steroids can have a anti inflammatory effect
Directly affect cells of the immune system to suppress or inflammatory responses
Inhibit the production of pro inflammatory cytokines
Promote production of anti inflammatory cytokines
Promote the apoptosis of T cells , macrophage and dendritic cells ,wading to a reduced immune response
Reduce Nk cell cytotoxicity
Recipe Bcell antibody production
Reduce expression of cell surface molecules responsible for T cell activation
Also implicated in regulating arachidonic acid metabolism
Increase transcription and translation of lipocortins
Suppress phospholipid A2 activity and suppress COX enzymes
Reduced production of inflammatory mediators
Beclomethasone diproprionate
Prodrug of beclometasone
Administered by inhalation
Half life -2,8 hrs
Prednisolone
Approved for treatment of wide range of inflammatory disease
Oral administration
Readily absorbed by GI tract
Half life 2-3 hours
Hydrocortisone
Main glucocorticoid secreted by adrenal cortex
Synthetic derivative administered by IV
used in emergencies
Half life 6-8 hrs
