Glucocorticoids Flashcards
Types of Adrenocorticoids
Glucocorticoids and Mineralocorticoids
Glucocorticoids:
_______ hormone
Increases ________ concentrations
Potent __________ effect
Stress; Glucose; Anti-inflammtory
Mineralocorticoids:
Regulates _________
Controls _________
Na/K+ level; Blood pressure
Adrenal Gland:
What comes from the Cortex?
Glucocorticoids; Mineralocorticoids; Androgens
Adrenal Gland:
what comes from the medulla?
Epinephrine and Norepinephrine
What is the HPA Axis
Hypothalamus Pituitary Adrenal Axis
1) Hypothal senses stress
2) Hypothal makes CRH
3) CRH goes to Ant. Pituitary
4) Ant. Pituitary makes ACTH
5) ACTH stimulates Adrenal gland
6) Adrenal gland makes cortisol
Stress Hormones: Epi vs. Cortisol
Epinephrine binds to what receptor?
Beta-adrenergic receptor (GPCR)
will stimulate GaS pathywat - more cAMP
Stress Hormones: Epi vs. Cortisol
Which one is immediate response and which one is long term response?
immediate: Epi
Cortisol: long term/has to regulate gene transcription
Stress Hormones: Epi vs. Cortisol
Cortisol binds to what receptor?
nuclear hormone receptor
Stress Hormones: Epi vs. Cortisol
Epi role in the body
breaks down glycogen/release insulin
Stress Hormones: Epi vs. Cortisol
Cortisol role in the body
induce gluconeogeneic enzymes
How does glucocorticoids affect the LIVER
increase gluconeogenesis and increase glycogen storage (because it becomes readily available glucose)
How does glucocorticoids affect the Muscle
promote protein degradation
decrease protein synthesis
decrease sensitivity to INSULIN
How does glucocorticoids affect the Adipose tissue
promote lipolysis (break down for energy) decrease sensitivity to insulin
Glucocorticoids reduce the sensitivity to insulin in what areas?
muscle and adipose tissues
How does glucocorticoids affect the immune system
blocks synthesis of cytokines and inhibits production of eicosanoids
leads to IMMUNOSUPRESSION AND ANTI-INFLAMMATION
Classic Model of Steroid Action:
Hormone binds to Hormone receptor and ______ is released; Then the hormone receptor will move to the _______ and work as a __________ factor
heat shock proteins; nucleus; transcription
Hormone receptors move to nucleus to affect transcription and do this by binding as a _______
dimer
what is the HRE
Hormone responsive elements - is where dimers bind on DNA
where is HRE found
upstream from steroid responsive genes
Glucocorticoids upregulate what kind of enzymes?
ones that cause gluconeogensis and anti-inflammatory proteins
what is lipocortin I?
it comes from glucocorticoids (somehow) and it will suppress phospholipase A2 –> will hault eicosanoid synthesis
what is NFkB?
it is Nuclear Factor kB - and it normally activates immune cells/causes cytokines to be made
when NFkB is inactive - it is bound to ________ and forms a _________
IkB; heterodimer
when the cell is under immune cell activation - what happens to NFkB?
IkB is removed from NFkB which allows NFkB to move to the nucleus and turn on transcription for cytokine genes
Relationship b/w glucocorticoids and NFkB?
activated glucocorticoid receptor will bind to NFkB and prevent NFkB from making cytokines via altering gene transcription
A __________ will sequester NFkB
GR-GR dimer
GR = glucocorticoid receptor
Best Type of Glucocorticoid for therapy =
- maximize _________ acitivity
- minimize _________ activity
- prevent _______ & ________
anti-inflammatory; mineralcorticoid; Cushing’s syndrome; Addisonian Crisis
Glucocorticoids vs. Mineralcorticoids
what 2 things are NEEDED for GC activity?
11-B hydroxyl
C17 hydroxyl
Glucocorticoids vs. Mineralcorticoids
What 2 things are required for BOTH (GC and MC)
4-5 double bond
C3 ketone
Which Synthetic Glucocorticoid?
has a 9a-F
Fludrocortisone
Which Synthetic Glucocorticoid?
used in mineralocorticoid replacement therapy
Fludrocortisone
Which Synthetic Glucocorticoid?
has extra double bond b/w C1/C2
Prednisone/Prednisolone
Which Synthetic Glucocorticoid?
Needs to be converted to its active form by the liver
Prednisone
Which Synthetic Glucocorticoid?
Which two are enantiomers of each other?
Dexmethasone and Betamethasone
Which Synthetic Glucocorticoid?
has a 6a-methyl group
methylprednisolone
triamcinolone has increased ____-ilicity
hydro–
dexamethasone has increased ____-ilicity
lipo–
Since Dexamethasone does have increased lipophilicity - how does it affect binding and effect
it has INCREASED RECEPTOR BINDING and STRONGER EFFECT
Glucocorticoids can be made into ProDrugs - they get activated ________ by _______
hydrolysis; esterases
Glucocorticoids & ProDrugs:
What are the types of ProDrug “side chain”/”add-ons”
Acetate/butyrate; Phosphate; Succinate
Glucocorticoids & ProDrugs:
How does Acetate/Butyrate affect the glucocorticoid
- increases LIPOPHILLICITY
- prolonged action/will stay at site LONGER
(via injection)
Glucocorticoids & ProDrugs:
How does Phosphate affect the glucocorticoid
- increases SOLUBILITY
- rapid hydrolysis
- OPTIMAL for IV or IM
Glucocorticoids & ProDrugs:
How does succinate affect the glucocorticoid
- soluble
- SLOW hydrolysis
Which adrenocorticoid(s) have the lowest MC activity (aka 0 on the chart he gave us..)
- methylprednisolone
- triamcinolone
- dexamethasone
- betamethasone
Which adrenocorticoid(s) have the highest MC activity
fludrocortisone
Adverse effects of Corticoids:
- if there is crossover mineralcorticoid activity…
- EDEMA via Na/Water retention
- development of HTN
Adverse effects of Corticoids:
what are the Cushing Like effects
Redistribution of fate aka
Moon face/Buffalo hump
-NON-REVERSIBLE
Adverse effects of Corticoids:
What are some metabolic effects
- steroid myopathy (lose muscle)
- reduced long bone growth in children
- osteoporosis
How can corticoids lead to osteoporosis
glucocorticoids inhibit OSTEOBLASTS (they normally BUILD BONES)
How to prevent osteoporosis from corticoids
bisphosphanates
Adverse effects of Corticoids:
GI effect?
greater peptic ulcer risk
Symptoms of Addisonian Crisis
- inability to withstand stress
- hypotension
- weakness
Why can Addisonian Crisis happen
its due to negative feedback on the hypothalamus and pituitary from prolonged doses of glucocorticoids
Which Inhaled Glucocorticoid?
has rapid metabolism by the liver
Flunisolide/Aerobid
