Glucocorticoids

Question 1

Describe the biological function of glucocorticoids

Answer 1

stress hormones
increase circulating glucose concentrations
potent anti-inflammatory effects

Question 2

Explain how the hypothalamus and the pituitary regulate the biosynthesis of cortisol

Answer 2

production of cortisol is regulated by hypothalamus

1- hypothalamus sense stress
2-hypothalamus releases CRH (corticotropin releasing hormone) in response to stress
3- ACTH (corticotropin) in adrenal gland releases cortisol

cortisol trigger physiological responses in the body
(-) feedback loop in the body

Question 3

Transcriptional Regulation by Glucocorticoids Mechanisms

ex: cortisol

Answer 3

cortisol binds to glucocorticoid receptor (nuclear hormone receptor)

regulates gene transcription-translation and protein production

induces long term persistent biological response

induces gluconeogenic enzymes

inhibits pro-inflammatory processes

steady long term stress response

Question 4

Asthma

Answer 4

generally due to inflammation of the bronchial airways

Question 5

Short Acting Treatments

Answer 5

provide rapid relief during an attack

Question 6

Long Term Treatments

Answer 6

help prevent future attacks

Question 7

Inhaled Glucocorticoids

Answer 7

most effective preventive agent

Question 8

Oral Glucocorticoids

Answer 8

only for severe cases due to considerable adverse effects

Question 9

Adrenocorticoids

Answer 9

glucocorticoids:
stress hormones
increasing circulating glucose concentrations
potent anti-inflammatory effects

mineralocorticoids:
regulates Na+/K+ levels
controls blood pressure

Question 10

Functions of Glucocorticoids

Answer 10

liver:
increase gluconeogenesis
increase glycogen storage

muscle:
promote protein degradation
decrease protein synthesis
decrease sensitivity to insulin

adipose tissues:
promote lipolysis
decrease sensitivity to insulin

immune system:
block the synthesis of cytokines (immunosuppression)
inhibits the production of eicosanoids
(anti-inflammation)

Question 11

Glucocorticoids (GC)

Answer 11

4,5- double bond is required for GC activity
C3 ketone is required for GC activity
11-beta-hydroxyl is required for GC activity
C17 hydroxyl is required for GC activity

Question 12

Mineralocorticoids (MC)

Answer 12

4,5-double bond is required for MC activity
C3 ketone is required for MC activity
11-beta-hydroxyl is less important for MC activity
C17 hydroxyl is not required for MC activity

Question 13

Crossover mineralocorticoid activity:

Answer 13

adverse effect of corticoids:

• Na+ and water retention
• development of HTN

correctable with selective synthetic glucocorticoids

Question 14

Metabolic Effects

(increased glucose production):

Answer 14

adverse effect of corticoids:

steroid myopathy
-high doses over periods of time causing wasting of proximal muscles

Question 15

Reduced long bone growth in children:

Answer 15

adverse effect of corticoids:

may cause premature closing of epiphyseal junction and stop growth

Question 16

Osteoporosis:

Answer 16

adverse effect of corticoids:

a pharmacological dose of glucocorticoids inhibit osteoblasts
-can be prevented by bisphosphonate

Question 17

Cushing’s-like effects:

Answer 17

adverse effect of corticoids:

moon face
buffalo hump

Question 18

Impaired glucose tolerance:

Answer 18

hyperglycemia from gluconeogenesis

decreased insulin response

Question 19

Suppression of the immune system:

Answer 19

increased susceptibility to infections

impaired wound healing

Question 20

greater peptic ulcer risk

Answer 20

adverse effect of corticoids

Question 21

euphoria or depression

Answer 21

adverse effect of corticoids

Question 22

cataracts

Answer 22

adverse effect of corticoids

Question 23

(Addisonian Crisis) adrenal Insufficiency upon withdrawal

Answer 23

adverse effect of corticoids

• due to negative feedback on hypothalamus and pituitary from prolonged pharmacological doses of glucocorticoids
• delayed recovery of hypothalamus and pituitary
• depressed ACTH release and adrenal response to ACTH
• directly related to dose and duration of therapy

symptoms: inability to withstand stress
hypotension
weakness

Question 24

Mechanisms of Glucocorticoid Action in Asthma

Answer 24

glucocorticoids will not stop an asthma attack while it is happening

effective in inhibitng airway inflammation

• modulation of cytokine and chemokine production
• inhibition of eicosanoid synthesis
• inhibition of accumulaton of immune cells in lung tissue
• decreased vascular permeability

inhaled glucocorticoids are used prophylactically to control asthma

Question 25

Inhaled Glucocorticoids

Answer 25

desired properties

• high potency
• minimal systemic effects -only want the drug to be in paients airways
• prolonged action

solutions:
high lipophillicty -decreases solubility
tighter binding to the receptor
better tissue penetration
prolonged action by forming poorly soluble microcrystals

low oral bioavailability:
70-90% of inhaled glucocorticoids is swallowed

rapid clearance:
short half life

reserved for moderate or severe asthma

Question 26

Inhaled glucocorticoids adverse effect:

Answer 26

systemic effects are neglible due to extremely low oral bioavilability (extensive first-pass metabolism by the liver)

• high doses, oropharyngeal candidiasis and dysphonia may occur
• candidiasis-prevention by washing mouth and throat with water after each use

decrease in bone mineral density may occur in females