Therapeutic Steroids

what hormones are produced from where?

Why are steoid called steroid

core chemical structure and diagnostic tests

What is the basi cstructure of a steroid

4 ringed structure with differenct functions, also have many different steps

What is teh exotics cortisol

Corticosteroe

Mineralcorticoid?

Aldosterone - mineral ie sodium…

What us a G vs M receptors

m and G receptors are NOT mutaully exclusice..

e.g. if too much cortisol may biind to M receptor causing a mineralcorticoid response

If this happens the body will use the enzyme 11 beta HSD to convert cortisol to cortisone to prevent it bindnig to the M receptors

What is the most common reason to use steroids

Inflammation

What are the theraputic effects of glucocorticoids..

• replacement( both)

• shock metabolic

• and for immune system suppression…

• do not hold if pregnant!!

What is the artificial cortisol and what is its half life, what is done to mitigate this…

• Hydrocortisone, 60 minute half life therefore need to try and increase the potency to make it more specific for the chosen receptor…

What are the 3 ways that steroids can have enhanced potency

C1-2 double bound

methylation

flourination

Why do you want drugs with a high potency

You do not want cortisol because cortisol has a LOW potency.. This is because it has a short half life and the body responds to cortisol anyway.. IF you have a synthetic version then teh potency will be increased and the body will have a reaction to it, e.g. immune suppression. if the drug is too potent then iatrogeniccushings may be caused..

What i the comparison between different steroids…

Dexamethosone = GLucocortioid ONLY

ALdosterone = Mineral corticoid ONLY

Methylprednisolone = both..

What is the biological conversion

11 beta HSD can convert cortisone = cortisol (more biologically acitve) ONE = ketone group - cortisol = alcohol group= activr form

enzymes can do this and this will increase activatin and can be a target site for steroid drugs..

What is another way to enhance a drugs half life

ESTERIFICATION - this will decrease solubility, the less soluble the steroid, the longer the half life will be..

Ester comparison table

• less soluble = longer acting

• Pay attention to administration route, ie Im/ IV

• understand ester-dependent absorption

What are the shor term side affects of glycocorticoid steroids and long term affects

• PU/ pd, hunger and liver enzyme induction.. Increas ALP and ALT

• sepsis and secondray infection due to low immune system , GI haemorrage - NO SURGERY otherwise the wound will not heal…

What will happen from metabolic cortisol affect…

• Iattogenic hyperadrenocorticism - cushingoif

• diabetes mellitus

NB cushings is NOT itchy, BUT secondary infections from suppressed immune systems may be…

What happens if there is too much negative feedback on teh HPA axis…

• GC withdrawn cannot make ACth so cant cope with stress

• long time to restart producing glucosteroids

What happens if you suddenly stop glucocorticoids

_ adrenal glands fail - glucocortico steroids

What happens if you stop mineral coticods

Angiotensin 2

no electrolyte disturbances

What are the signs and symptoms from steroid withdrawral..

• depression

• anorecia

• vommiting

• abdominal discomfort

How do you mitigate risk of iatrogenci hyperadrenocistiam

• min dose

• least potent

• short acting

• intermittent dosing

• tapered therapy

What happens when you stop giving drugs…

Tapering..

What are the implications for diagnostic tests from exogenouc glucocorticoids

On the graphs, brown boxes highlight the results of a normal ACTH stimulation test. The lines show the results of the ACTH stim test in iatrogenic hyperadrenocorticism and primary hypoadrenocorticism.

Analytical implicatioins for diagnostic testing…

§Prednisolone and Cortisol are structurally similar enough that immunoassays for cortisol will pick up prednisolone in serum and give false high values

§Dexamethasone is different enough that it does not interfere with serum cortisol measurement

§That’s why we have dexamethasone suppression tests and not prednisolone suppression tests

How do you know if HAC is from an exogenous steroid…

ONLY acth is from IAtrogenic hyperadrenocorticism