Adrenal Pharmacology Flashcards
Tx for adrenal insufficiency
- Two types
Glucocorticoid replacement for >3 weeks (Primary and secondary)
- Hydrocortisone
- Prednisone
- Dexamethasone
Mineralocorticoid Replacement (primary only) 1. Fludrocortisone (aldosterone analog)
*secondary: no ACTH, not cortisol or aldo
Side effect of exogenous glucocorticoids
+
Mineralocorticoids
Gluco: Iatrogenic cushings
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Mineralo:
HTN,
Hypokalemia
Met alkalosis
due to increase secretion of H+ and K+ in distal tubules
~~~
Target for Cushing’s disease
CYP11B1
CYP17
Glucocorticoid metabolic effect vs Excess effects (ie: pharmacologic)
- Carbohydrate
- Protein
- Fat
*GLUCOcorticoid, think more GLUCOSE (for supply to brain)
- Carbohydrate
↑ gluconeogenesis → ↑ blood glucose (↑ insulin)
Excess: diabetes like state (Cushings) - Protein
↓ protein synth → ↑ AA for glucose
Excess: muscle wasting - Fat
↑ lipolysis (peripherally) → ↑ FFA
Excess: ↑ lipogenesis (central obesity)
Adverse effects of pharmacologic doses with prednisone: (but not dexamethasone, which is an effective activator by eliminating MC activity)
Elevated blood pressure
Hypokalemia
*mediated by mineralocorticoid R,
(not glucocorticoid receptor - dex)
Upside of glucocorticoids vs Downside
Upside:
GCs suppress chronic inflammation and autoimmune rxns
(Antiinflammatory-Immunosuppressive effects)
Downside:
GCs decrease healing, and diminish immunoprotection
Mineralocorticoid effects
- normal metabolic vs pharm
↑ 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
True/false
For adrenal insufficiency, Prednisone requires hepatic activation and is ONLY effective given via oral route
true
True/False
For adrenal insufficiency, Hydrocortisone in twice daily dosing is sufficient for most patients with Addison’s disease
True
*need to tx pts with Addisons with both glucocorticoid and mineralocorticoid activity.
(dexameth, and triamcinolone no good)
Cushings syndrome tx
ACTH secretion inhibitors
Cortisol synthesis inhibitors
Adrenolytic Agents
Cortisol receptor blockers
ACTH secretion inhibitors
Cortisol synthesis inhibitors
used to treat cushings syndrome
ACTH secretion inhibitors
- Cabergoline (D2 agonist) , Pasireotide (SST analog)
Cortisol synthesis inhibitors
- ketoconazole
Adrenolytic Agents
Cortisol receptor blockers
used to tx cushings
Adrenolytic Agents
- Mitotane
Cortisol (glucocorticoid) receptor blockers
- mifepristone (progesterone R inhibitor)
In pts with adrenocortical insufficiency, when do you give IV hydrocortisone vs dexamethasone?
Acutely, there are electrolyte abnormalities and plasma volume depletion
If there was prev. dx:
Large amts of hydrocortisone enough
W/o previous dx:
dexamethasone
Effect of aldo antag (diuretic agent) on plasma electrolyte
HYPERkalemia
CCBs
Dihydropyridines (nefedipine)
Diltiazem
Verapamil
Amilioride and Triamteren effect on aldosteronism
Sodium channel blocker
- Blocks Na+ reabsorption
- Prevents K+ reabsorption from blood into cell
(charge balance)
Can control hypokalemia of IHA
Tx of pheochromocytoma (pre-operative)
1st: alpha blocker
2nd: Beta blocker
ALone: CCB
THEN surgery
- alpha blockers:
- Phenoxybenzamine
- prazosin
- terazosin
- Doxazosin
- bb
- metoprolol
- labetalol
- ccb:
- nefedipine
Phenoxybenzamine
Terazosin-Doxazosin
Phenoxybenzamine
- irreversible a1-a2 R antag
Terazosin-Doxazosin
- reversible a1 R antagonist
(both can be used as prep for pheochromocytoma surgery)
Metoprolol
Labetalol
Metoprolol
- b1 blocker following alpha blocker
Labetalol
- a1-b1-b2 blocker
Prenisolone
Exogenous glucocorticoid (used in therapy)
- peripheral actions (metabolic, antiinflammatory, immunosuppressive)
- neg inhibitor of hypothalamus and ant pit.
Metyrapone + mitotaine
inhibits synthesis of glucocorticoids in adrenal cortex
GCC and MCC effects can be separate but we should that that GCC effects ______.
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
(Pick one: cortisone, cortisol, activating, inactivating)
The liver converts _____ to ______ .
____ step
Kidney converts ______ to ______.
____ step
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
Tx of choise for Cushing’s syndrome (hypercortisolism)
Surgery
Pharm is reserved for adjunctive therapy in refractory or inoperable cases
- glucocorticoid synthesis inhibitors
- glucocorticoid receptor antagonist
- keotoconazole
