PDA 1 exam 2 (adrenocorticoids)

What classes of hormones does the cortex produce?

1. mineralocorticoids

2. glucocorticoids

3. androgens

What do the cortex hormones do?

• mineralocorticoids

  • salt balance

• cortisol

  • endogenous glucocorticoids

  • increase nutrient availability

• androgen

  • DHEA

Where is most of cortisol in blood bout to?

transcortin- CBG (corticosteroid-binding globulin)

Do synthetic glucocorticoids bind to CBG?

not well because they are more potent and have less protein binding

What metabolic effect do corticosteroids have?

• increase blood glucose

• increase amino acids

• increase triglycerides

maintain energy supplies to critical organ during stress

Glucocorticoids feedback inhibition

• CHR stimulates release of ACTH

• ACTH stimulation reason of cortisol

• cortisol inhibits farther release of CRH and ACTH

sever stress can disrupt homeostasis

• receptor is desensitized

• cortisol resistance

• adrenal fatigue

What is the anti inflammatory effect of cortisol used to treat?

asthma

allergy

rheumatoid arthritis

organ transplant

Corticosteroids potency comparison

• fluticasone, triamcinolone, prednisone

• dexamethasone, betamethasone

• cortisol

dexamethasone, betamethasone > prednisolone, triamcinolone, fluticasone > cortisol

S or I or L DOA

hydrocortisone and cortisone

short

S or I or L DOA

prednisone, prednisolone, methylprednisolone, triamcinolone, and fluticasone

intermediate

S or I or L DOA

betamethasone and dexamethasone

long

Cortisol, prednisone, methylprednisolone and dexamethasone are (active or inactive) what kind of glucocorticoids?

they are active 11-hydroxy glucocorticoids

prednisone and cortisone are inactive. What must they be activated by?

11 keto pro drugs

must be activated by 11β- HSD 1

What body part has a high level of 11β- HSD 1?

Liver

11- keto —> 11- OH

cortisone to cortisol

What body part has a high level of 11β- HSD 2?

kidney

What does 11β- HSD 2 do?

converts active cortisol or inactive cortisone

OH —> keto

Who is the most common use for glucocorticoids?

suppress inflammation and immune response

Should you suddenly stop steroid therapy?

no, do a gradual decrease

• Long-term use complication

  • depacy ACTH production

  • adreanal atrophic and unresponsive

Addison disease

hypo or hyper corticolism

hypo

Addison disease

Primary adrenal insufficiency: symptoms and tx

• autoimmune reaction - destruction of adrenal cortex

• infection

• surgical removal of adrenal glands

Addison disease

secondary adrenal insufficiency: symptoms and tx

hypothalamic or pituitary disorder

abrupt stoppage of long-term glucocorticoids

Addison disease

causes

chronic adrenal insufficiency

Addison disease

tx

relacing/ substituting glucocorticoids and mineralocorticoids

Addison disease

salt craving

• cannot retain sodium

• no aldosterone to maintain sodium in kidney

• constant sodium leak

Cushing’s syndrome

hypo and hyper cortisolism

hyper

Cushing’s syndrome

cause

hypersecretion of glucocorticoids

Cushing’s syndrome

tx

surgery, radiation, chemotherapy

cortisol inhibition drugs

Cushing’s syndrome

pituitary

secondary- pituitary ACTH producing adenomas

70% of cases

Cushing’s syndrome

adrenal

primary- adrenal gland tumor

adrenal hyperplasia

Cushing’s syndrome

symptoms

• fat pads

• moon cheeks

• poor wound healing

• poor muscle development

glucocorticoids contraindications

• HTN and heart disease

• infection

• psychoses

• DM

• osteoporosis

• glaucoma

• PUD

regulation of aldosterone biosynthesis

• renin-angiotenin

  • increase aldosterone

• potassium ion loading

  • increase aldosterone

• ACTH

  • increase aldosterone

renin angiotensin system

• renin converts angiotensinogen —> angiotensin I

• angiotensin I —> angiotensin II by ACE (lung)

angiotensin II stimulation aldosterone synthesis

Fludrocortisone

what does it treat?

hypoaldosteronism (addisons)

Fludrocortisone

What kind of mineralocorticoid?

mineralocorticoid receptor agonist

Fludrocortisone

Does it have 1st pass metabolism?

very minimal

why we use it instead of aldosterone

Fludrocortisone

adverse effects

• hypokalemia

• HTN

Spironolactone

What kind of mineralocorticoid?

mineralocorticoid receptor blocker

androgen recepot blocker

Spironolactone

What is it used for?

hyperaldosteronism

hirsutism

acne

HTN (reabsorption is decreased)

mitotane

• used for cushings’s (adrenocortical inhibitors)

• for adrenal carcinoma

• many adverse effects, or compassionate use only

ketoconazole

• for Cushing (adrenocortical inhibitors)

• antifungal imidazole

• high does- nonselective inhibitor or adrenal and sex steroid synthesis

• can lower cortisol

• has liver toxicity

mifepristone

• for cushing’s (adrenocortical inhibitors)

• glucocorticoids and progesterone antagonists

• abortion

metyrapone

• pregnant women with cushings’s

• 11B hydrolase

osildrostat (Isturisa)

• cushings in adults

• 11B hydrolase

• inoperable tumor

• ineffective surgery

baxdrostat (Baxfendy)

• HTN

• 11B hydrolase 2