Lec 28 Adrenal cortex

What increases duration of action in glucocorticoids analogues

Highr plasma protein binding

Lower affinity for 11beta HSDII

Higher lipophilicity

Higher affinity for GR

Glucocorticoids and Pregnancy

Mother can be given prednisone without SEs in fetus

• Metabolism: The mother's liver converts prednisone into prednisolone, which is a more active form of the medication. However, the placenta contains an enzyme called 11β-HSDII which can convert prednisolone back to the less active prednisone.

• Fetal metabolism: The fetal liver is unable to convert prednisone back into prednisolone, which means that the active drug does not accumulate in the fetus, reducing potential side effects.

Dexamethasone or betamethasone give to promote fetal lung maturation

Immune suppression mechanisms

1)Inhibition of COX2 and phospholipase A2—>Inhibits conversion of arachidonic acid to prostaglandins and leukotrienes

2)Inhibition of cytokine production and release

3)Reduced expression of ELAM1 and ICAM 1 adhesion molecules—>reduces recruitment of immune cells

4)Inhibit histamine & leukotriene C4 release

Mitotane

Selectively adrenocortical cells

Must replace both cortisol & aldosterone deficit

Aminoglutethimide

Inhibits CYP11A1 to reduce all adrenosteroids

Inhibits CYP11B1 and aromatase

Glucocorticoid replacement encessary but do NOT use dexamethason

Ketoconazole

Inhibits CYP17 and CYP11A1

Serious drug interactions, hepatic dysfunction

treat cushings

Metyrapne

Selective CYP11B1 inhibitor

Mifepristone

Progesterone receptor antagonist at LOW concentrations

Glucocorticoid recepor antagonist at HIGH concentrations

use: treat life threatening glucocorticoid levels in ectopic ACTH syndrome

Emergency contraceptive

Aldosterone effects

Na reabsorption

K excretion

Aldosterone hypofunction effects

Salt wasting

Hyperkalemia

Acidosis

Aldosterone hyperfunction effects

Volume expansion

Hypokalemia

Alkalosis

Hypertension

Mineralocorticoid receptor antagonists

Spironolactone

Eplerenone

Fludrocortisone

Mineralocorticoid receptor agonist

High mineralocorticoid: glucocorticoid potency ratio

Aldosterone repalcement therapy

Congenital adrenal hyperplasia & PCOS

Increased DHEA- a precusor to testosterone