Adrenal Pharmacology

Because ritonavir inhibits CYP3A4 - enzyme involved in the metabolism of corticosteroids.

They can cause osteopenia/osteoporosis because they suppress bone remodeling and decrease calcium reabsorption.

• taper off!
• Adrenal suppression makes this a must-do or the pt will crash

A Non-selective adrenal steroid synthesis inhibitor - to reduce cortisol levels

net effect - all of aldosterone, cortisol and androgens will be reduced

CYP450 inhibitor. Major 3A4 inhibitor therefore hepatotoxicity is a major concern.

Can have antiandrogenic effects since it reduced androgens too. i.e. gynecomastia in males

Blocks 11B hydroxylase to decrease cortisol

blocking 11Bhydroxylase causes the buildup of 11deoxycortisol which is an aldosterone receptor agonist - can therefore cause hypertension

May also increase androgens - hirsutism in females

Blocks rate-limiting conversion of cholesterol to prenenolone and increases steroid clearance.

Non-selective and will decrease other adrenal hormones. Therefore it's often used in conjunction with metyrapone

Non-selective blocker of several steps in the synthesis of cortisol and aldosterone

Wipes out adrenal. Several. Also low TI, therefore only used as a 3rd line tx. Sometimes used in carcinomas and secondary cushing's like lung cancer if otherwise inoperable and other therapies fail

blocks thyroxine synthesis - hypothyroidism

Induced CYP3A4 - possible drug interactions

May be too effective in combo with metyrapone - adrenal insufficiency

• activates glucocorticoid receptors??
• Given in two doses to mimic natural cycle of cortisol

• it's a hydrocortisone agonist. Specific for the aldosterone receptor.
• It activates the mineralocorticoid receptor to increase the expression of the Na/K ATPase.

Increases salt retention, and K excretion - necessary in Addison's if oral hydrocortisone has insufficient MR activity

If the dose is too high, it can cause edema/hypertension, and hypokalemia.

Hypokalemia predisposes pt to cardiac events