Adrenal Pharmacology

Question 1

Tx for adrenal insufficiency

- Two types

Answer 1

Glucocorticoid replacement for >3 weeks (Primary and secondary)

1. Hydrocortisone
2. Prednisone
3. Dexamethasone

Mineralocorticoid Replacement (primary only)
1. Fludrocortisone (aldosterone analog)

*secondary: no ACTH, not cortisol or aldo

Question 2

Side effect of exogenous glucocorticoids
+
Mineralocorticoids

Answer 2

Gluco: Iatrogenic cushings

```
Mineralo:
HTN,
Hypokalemia
Met alkalosis
due to increase secretion of H+ and K+ in distal tubules
~~~

Question 3

Target for Cushing’s disease

Answer 3

CYP11B1

CYP17

Question 4

Glucocorticoid metabolic effect vs Excess effects (ie: pharmacologic)

1. Carbohydrate
2. Protein
3. Fat

Answer 4

*GLUCOcorticoid, think more GLUCOSE (for supply to brain)

1. Carbohydrate
   ↑ gluconeogenesis → ↑ blood glucose (↑ insulin)
   Excess: diabetes like state (Cushings)
2. Protein
   ↓ protein synth → ↑ AA for glucose
   Excess: muscle wasting
3. Fat
   ↑ lipolysis (peripherally) → ↑ FFA
   Excess: ↑ lipogenesis (central obesity)

Question 5

Adverse effects of pharmacologic doses with prednisone: (but not dexamethasone, which is an effective activator by eliminating MC activity)

Answer 5

Elevated blood pressure

Hypokalemia

*mediated by mineralocorticoid R,
(not glucocorticoid receptor - dex)

Question 6

Upside of glucocorticoids vs Downside

Answer 6

Upside:
GCs suppress chronic inflammation and autoimmune rxns
(Antiinflammatory-Immunosuppressive effects)

Downside:
GCs decrease healing, and diminish immunoprotection

Question 7

Mineralocorticoid effects

- normal metabolic vs pharm

Answer 7

↑ Na+ reabsorption at kidney → ↑ blood volume and BP
(Na retaining actions)

excess: Fluid retention, HYPERtension, HYPOkalemia

Peripheral action on salt and water metabolism

*fludrocortisone is a mineralocorticoid

Question 8

True/false

For adrenal insufficiency, Prednisone requires hepatic activation and is ONLY effective given via oral route

Answer 8

true

Question 9

True/False

For adrenal insufficiency, Hydrocortisone in twice daily dosing is sufficient for most patients with Addison’s disease

Answer 9

True

*need to tx pts with Addisons with both glucocorticoid and mineralocorticoid activity.
(dexameth, and triamcinolone no good)

Question 10

Cushings syndrome tx

Answer 10

ACTH secretion inhibitors

Cortisol synthesis inhibitors

Adrenolytic Agents

Cortisol receptor blockers

Question 11

ACTH secretion inhibitors

Cortisol synthesis inhibitors

used to treat cushings syndrome

Answer 11

ACTH secretion inhibitors
- Cabergoline (D2 agonist) , Pasireotide (SST analog)

Cortisol synthesis inhibitors
- ketoconazole

Question 12

Adrenolytic Agents

Cortisol receptor blockers

used to tx cushings

Answer 12

Adrenolytic Agents
- Mitotane

Cortisol (glucocorticoid) receptor blockers
- mifepristone (progesterone R inhibitor)

Question 13

In pts with adrenocortical insufficiency, when do you give IV hydrocortisone vs dexamethasone?

Answer 13

Acutely, there are electrolyte abnormalities and plasma volume depletion

If there was prev. dx:
Large amts of hydrocortisone enough

W/o previous dx:
dexamethasone

Question 14

Effect of aldo antag (diuretic agent) on plasma electrolyte

Answer 14

HYPERkalemia

Question 15

CCBs

Answer 15

Dihydropyridines (nefedipine)
Diltiazem
Verapamil

Question 16

Amilioride and Triamteren effect on aldosteronism

Answer 16

Sodium channel blocker
- Blocks Na+ reabsorption
- Prevents K+ reabsorption from blood into cell
(charge balance)

Can control hypokalemia of IHA

Question 17

Tx of pheochromocytoma (pre-operative)

Answer 17

1st: alpha blocker
2nd: Beta blocker

ALone: CCB

THEN surgery

• alpha blockers:
• Phenoxybenzamine
• prazosin
• terazosin
• Doxazosin
• bb
• metoprolol
• labetalol
• ccb:
• nefedipine

Question 18

Phenoxybenzamine

Terazosin-Doxazosin

Answer 18

Phenoxybenzamine
- irreversible a1-a2 R antag

Terazosin-Doxazosin
- reversible a1 R antagonist

(both can be used as prep for pheochromocytoma surgery)

Question 19

Metoprolol

Labetalol

Answer 19

Metoprolol
- b1 blocker following alpha blocker

Labetalol
- a1-b1-b2 blocker

Question 20

Prenisolone

Answer 20

Exogenous glucocorticoid (used in therapy)

• peripheral actions (metabolic, antiinflammatory, immunosuppressive)
• neg inhibitor of hypothalamus and ant pit.

Question 21

Metyrapone + mitotaine

Answer 21

inhibits synthesis of glucocorticoids in adrenal cortex

Question 22

GCC and MCC effects can be separate but we should that that GCC effects ______.

Answer 22

GCC effects can NOT be separated from ANTI-INFLAMMATORY effects and antiinflammatory effects can NOT be separated from IMMUNOSUPPRESSIVE EFFECTS.

*so think of these activities as interchangeable

Question 23

(Pick one: cortisone, cortisol, activating, inactivating)
The liver converts _____ to ______ .
____ step

Kidney converts ______ to ______.
____ step

Answer 23

The liver converts CORTISONE to CORTISOL.
-Activating step

Kidney converts CORTISOL to CORTISONE.
- Inactivating step (protects kidney from cortisol activity)

*can treat moms with glucocorticoids w/o effect on fetus bc placental enzyme can convert active drug back to prodrug

Question 24

Tx of choise for Cushing’s syndrome (hypercortisolism)

Answer 24

Surgery

Pharm is reserved for adjunctive therapy in refractory or inoperable cases

• glucocorticoid synthesis inhibitors
• glucocorticoid receptor antagonist
• keotoconazole