Adrenal glands and Corticosteroids as drug targets

Question 1

what is cortisol?

Answer 1

a glucocorticoid

Question 2

effect of cortisol?

Answer 2

raises blood sugar, protein/ fat metabolism

Question 3

what is aldosterone?

Answer 3

mineralocorticoid

Question 4

effect of aldosterone?

Answer 4

increases serum Na, raises BP

Question 5

what are the effects of androgen precursors?

Answer 5

maturation and development

Question 6

where are the adrenal glands?

Answer 6

sit on top of the kidneys

Question 7

what happens if you lose an adrenal gland?

Answer 7

if you lose one the other ups its game

Question 8

3 parts of the adrenal gland? and functions?

Answer 8

outer capsule- where the blood vessels land and deviate
adrenal cortex- produces steroids
adrenal medulla- cathecholamine prosecution

Question 9

is the adrenal cortex electrically active?

Answer 9

no

Question 10

is the adrenal medulla electrically active?

Answer 10

yes

Question 11

3 regions of the adrenal cortex?

Answer 11

zona glomrulosa- closest to the capsule
zona fasiculata
zona reticularis

Question 12

which zones produce the corticosteroids?

Answer 12

zona glomerulosa- aldosteron

zona fasiculata- cortisol

Question 13

what does the zone reticularis produce?

Answer 13

produces adrenal androgens

Question 14

what are adrenal androgens the primary precursors for?

Answer 14

testosterone

oestrogen

Question 15

in steridogenesis within the adrenal cortex, are the steroids synthesised and stored?

Answer 15

no, synthesised on demand from cholesterol

Question 16

what is the rate limiting step of sterroidogenesis?

Answer 16

cholesterol–> pregnenolone

Question 17

what is the basic steroid backbone?

Answer 17

17 carbon resides

4 ring

Question 18

what stimulates the conversion of cholesterol to pregnenolone?

Answer 18

ACTH stimulates the induction of pregnenolone synthase

Question 19

physiological actions of adrenal steroids: glucocorticoids?

Answer 19

metabolic effects- glucose like effects
anti-inflammatory
immunosuppressive

Question 20

physiological actions of adrenal steroids:

mineralcorticoids

Answer 20

water and electrolyte balance- associated with Na conservation and raising of extracellular volume to fight low BP

Question 21

physiological actions of adrenal steroids:

adrenal androgens

Answer 21

maturation and development- key precursors for oestrogen and testosterone

Question 22

what is transcortin?

Answer 22

corticosteroid binding globulin

binds 90% of cortisol and 60% of aldosterone

Question 23

does transporting bind synthetic steroids?

Answer 23

no

Question 24

what does albumin bind?

Answer 24

synthetic and natural steroids

Question 25

what are the actions of steroids?

Answer 25

changes in transcription and translation | altering the synthesis of specific proteins

Question 26

why can this alteration of proteins by steroids take a while?

Answer 26

have to change protein turnover and get into the DNA- roughly 20-30 minutes

Question 27

can aldosterone have quick effects on protein synthesis? why?

Answer 27

yes due to receptors on the cell surface

Question 28

explain to steps to cortisol release when you get an emotional response?

Answer 28

emotional response (stress/ excitement etc) activates the hypothalamus hypothalamus releases CRH which stimulates the release of ACTH from the pituitary this then enters the circulation and reaches the adrenal cortex where it stimulates pregnenolone synthase the synthesis of cortisol then begins.

Question 29

does cortisol release from an emotional response experience negative feedback?

Answer 29

yes- switches of ACTH production and CRH production

Question 30

effects of cortisol in an emotional response?

Answer 30

``` Promoting lipolysis Promoting gluconeogenesis Protein catabolism Sensitizing blood vessels Reducing inflammation ```

Question 31

do mineralcorticoid have wide tissue distribution?

Answer 31

no- limited

Question 32

effect of mineral corticoids?

Answer 32

causes NA uptake, leading to fluid resorption and K loss

Question 33

what can act as a competitive inhibitor of mineralocorticoid receptors

Answer 33

spironolactone

Question 34

what does spironolactone treat?

Answer 34

hypertension | diuretic

Question 35

what happens when aldosterone is released?

Answer 35

it increases BP by increasing salt retention when bp falls, renin converts angiotensin 1------> antiotension 2 a2 causes constriction and raises BP

Question 36

what does Angiotensin 2 cause?

Answer 36

vasoconstriction and raises BP

Question 37

short acting synthetic steroids?

Answer 37

hydrocortisone | fludrocortisone

Question 38

how long is the half life of hydrocortisone and fludrocortisone?

Answer 38

short acting | t1/2 is 8-12 hours

Question 39

intermediate acting synthetic steroids examples?

Answer 39

prednisolone

Question 40

how long is the half life of prednisolone?

Answer 40

12-36 hours | intermediate

Question 41

long acting synthetic steroids examples?

Answer 41

dexamethasone and betamethasone

Question 42

how long is the half life of dexamethasone and betamethasone

Answer 42

36-72 hours | long acting

Question 43

what does chemical modification of steroids influence?

Answer 43

the selectivity

Question 44

examples of steroids which have GC and MC activity?

Answer 44

prednisolone

Question 45

examples of steroids with pure GC activity?

Answer 45

dexamethasone, betamethasone, beclomethasone

Question 46

examples of steroids with pure MC?

Answer 46

fludrocortisone

Question 47

TF: it is easy to remove the anti-inflammatory responses in synthetic steroids?

Answer 47

false

Question 48

THERE IS AN IMPORTANT STRUCTURE OF STEROID AND THEIR ACTIVITY IN THIS LECTURE YOU NEED TO LEARN!

Answer 48

LEARN

Question 49

what is an example of a hypo function of steroids?

Answer 49

Addisons disease

Question 50

what is the Addisons mnemonic?

Answer 50

``` A: appetite loss and weight loss D: discolouration of the skin D: Dehydration I: increased thirst S: salt, soy sauce and liquorice cravings O: oligomenorrhoea: irregular periods N: no energy S: sore muscles ```

Question 51

what is the adrenal crisis in Addisons disease?

Answer 51

profound fatigue dehydration vascular collapse renal shutdown

Question 52

Addisons: adrenal crisis: _____ serum NA _____ serum K

Answer 52

decreased | increased

Question 53

treatment of addisons?

Answer 53

hydrocortison (GC) with or without fludrocortisone (MC)

Question 54

why does the treatment of Addisons by hydrocortison with or without fludrocortisone have limited side effects?

Answer 54

mimics natural plasma levels

Question 55

what is an example of hyper function?

Answer 55

congenital adrenal hyperplasia- overproduction

Question 56

what happens in untreated congenital adrenal hyperplasia?

Answer 56

androgens are over produced and the other hormones aren't as there's no cortisol made, they cant switch off as cortisol is what causes negative feedback. there is a drive from the CRH and ACTH but no switching off by cortisol

Question 57

what is treatment for congential adrenal hyperplasia?

Answer 57

exogenous cortisol

Question 58

how does exogenous cortisol treat CAH?

Answer 58

replaces lost cortisol that's not made | brings back endocrine/ physiological control by switching negative feedback on

Question 59

why can steroids be used as an anti-inflammative/ immunosuppressant?

Answer 59

reduce mediators of inflammation and immune responses including: cytokines, PGs, NO, IgG

Question 60

applications for steroids when used for their anti-inflammative/ immunosuppressant effect?

Answer 60

``` asthma eczema arthiritis psoriasis allergies itching ```

Question 61

steroid agents used for anti-inflammative/ immunosuppressant

Answer 61

hydrocortisone, prednisolone, beclomethasone, dexamethasone, budesonide, etc

Question 62

what are the inappropriate metabolic influences of excessive glucocorticoid administration/ use?

Answer 62

drug induced Cushing syndrome | oesteoperosis

Question 63

do you get an increased risk of infection with GC?

Answer 63

yes- powerful anti-inflams

Question 64

side effects of inhaled GCs?

Answer 64

thrush- growth of opportunistic Candida albicans

Question 65

how can thrush be reduced when using inhaled GCs?

Answer 65

using spacer of rinsing the mouth after use

Question 66

symptoms of Cushing syndrome?

Answer 66

``` increased abdominal and face fat lipolysis red round moon face hypertension/ glycaemia vertigo blurry vision acne female balding water retention menstural irregulatities thin skin poor wound healing osteoporosis muscle wasting purple striae depression ```

Question 67

what is a treatment of hyper function of steroids?

Answer 67

inhibition of steroid synthesis: aminoglutethimide selective inhibition: metyrapone

Question 68

mechanism of action of aminoglutethimide?

Answer 68

inhibits enzymes in the pathway | reduces steroidal output from adrenal cortex

Question 69

aminoglutethimide is used to treat?

Answer 69

Cushings- hyper activation disorder postmenopausal breast cancer prostate cancer

Question 70

metyrapone mechanism of action?

Answer 70

selective inhibitor inhibits 11b-hydroxylase reduces GC and MC synthesis

Question 71

what does metyrapone treat?

Answer 71

bushings | hyperaldosteronism

Question 72

side effects pf metyrapone?

Answer 72

hirsutism in women due to excessive androgens

Question 73

how can metyrapone test anterior pituitary function?

Answer 73

decreased GC will also decrease negative feedback drive and increase levels of ACTH IF YOU MEASURE THE acth levels whilst giving this drug you can see if an individual has an issue with the pituitary gland if you fail to get the negative feedback mechanism it would indicate there's tumour in the pituitary

Question 74

how can tetracosatide/ synacthen be used to test for adrenal insufficiency?

Answer 74

they are ACTH mimetic stimulates synthesis and release of adrenal hormones