Adrenal Pharmacology Flashcards
General Uses of GC
Anti-inflammatory (GC only)
Immunosuppressive (GC only)
Physiologic replacement (Both GC & MC)
Tx of adrenal insufficiency (Addision’s)
-Chronic: Cortisol (GC replacement) fludrocortisone (MC replacement) DHEA (sex steroid replacement in women) -Acute (adrenal crisis: hyponatermia &hyperkalmeia): IV cortisol (IF PREVIOUS Dx) or dexamethasone(w/out previous Dx)
Cushing’s Tx Hypercortisolism
- If due to tumor: remove it
- ACTH secretion inhibitors (Cabergoline & Pasireotide)
- Cortisol Synthesis inhibitors (Ketoconazole, Metyrapone, etomidate)
- Cortisol receptor anatgonist: Mifepristone
Congenital Adrenal Hyperplasia Mutations
-21 hydroxylase def: inc. androgens & dec MC=hypotension
-17alpha hydroxylase: no androgens, inc MC=HTN
-11beta hydrooxylase: inc androgens & inc MC=HTN
Cortisol almost always absent=inc ACTH (no suppression)
Preop management of pheochromocytoma
- First give: alpha blockers (phenoxybenzamine, pazosine, Terazosin, Doxazosin)
- Then Give: Beta Blockers (metoprolol)
- CCB (alone i.e. nifedipine)
Anti-inflammatory effects of GC
- inhibits Phospholipase A2 (no arachidonic acid)
- Inhibits COX2 (down regulation of PG, Tx, LT, LX: all eicosanoids)
Immunpsuppressive effects of GC
- Suppress T-cell activation
- Suppress cytokine production
- Prevent mast cell and eosinophil from releasing mediators (His, PG, LT)
Overall effect of GC
- Reduced vasodilation
- Decreased fluid exudation
- Decreased accumulation/activation of immune cells
11beta-HSD1
- Found in Liver
- Activating (Ketone->OH)
- Not present in fetus
11beta-HSD2
- Found in Kidney
- Inactivating (OH->Ketone): protects kidney from unreg MC activity.
- Present in Placenta
Metabolic effects of Cortisol (physiologic)
- Increase gluconeogenesis (Increase blood Glu)
- Lower protein synthesis (Increase AA to Glu)
- Increase lipolysis (Increase FFA)
effects of Aldosterone (physiologic)
- Increase Na+ reabsorption at kidney (Increase blood volume and BP)
- loosely coupled to K+ and H+ secretion
SE of Excess GC use
- Diabetes like state
- Muscle wasting. skin-connective tissue atrophy
- increase central lipogenesis (insulin action): Centripetal obesity (moon facies, buffalo hump)
SE of MC use
Known as “salt retaining” effects
- Increased Na+:increase BP
- Increased water: edema
- Increased K+ and H+ secretion: hypokalemia and metabolic alkalosis
Adverse Effects of high, sustained GC therapy
-Iatrogenic Cushing’s syndrome (too much GC,
get extreme GC side effects)
-HPA axis suppression (insuff response to
stress)
-Mood disturbance (initial euphoria, then
psychic letdown when dose reduced;
insomnia)
-Impaired wound healing (due to catabolism
of collagen/fibroblasts)
-Increased susceptibility to infection
Adverse effects seen w/ very large doses of GC
- Osteoporosis (risk dec by bisphosphonates)
- Posterior capsular cataracts (esp in children receiving prolonge asthma treatment)
- Skin atrophy/loss of collagen support
- Growth retardation in kids
- peptic ulcers
Oral GC agents
- pro-drug: prednisone, cortisone
- has ketone at carbon 11
- must be metabolized to active OH
Topical GC agents
cortisol (hydrocortisone) is already
active
IV GC agents
prednisolone=activated
prednisone
Hydrocortisone (cortisol)
- Physiologic replacement (equal GC/MC activity) and in emergencies
- oral and parenteral
Prednisone
- Most common oral agent
- Activated to prednisolone via 1st poss in liver
- no topical effect
- GC:MC activity is 13:1
Can you separate MC actions from GCC actions?
yes (dexamethasone), but can NOT separate anti-inflammatory from GCC actions & can NOT separate anti-inflammatory from immunosuppressive actions
Tx of primary aldosteronism (APA)
Preop (aldosterone antagonists)
- Spironolactone
- Eplerenone
Tx of primary aldosteronism (IHA)
Aldosterone antognists PLUS BP meds (CCB, ACEI, ARB)
Congenital Adrenal Hyperplasia
- Cortisol synthesis is diminished leads to increased ACTH (loss of GC feedback inhibition) leads to adrenal hyperplasia
- Can be accompanied by excess or deficiency of adrenal mineralocorticoids or androgens
GC anti-inflammatory use dosing considerations
- Reduce dosage as soon as therapeutic objectives are obtained
- Large doses: use shorter-acting agent with little MC
- Alternate day schedule: minimize adrenal suppression
- Anti-inflammatory actions outlast HPA suppression
- Terminate administration gradually (duration > 7-28 d) to minimize disease rebound and symptoms of adrenal insufficiency (adrenal crisis)
Methylprednisone
Best if want parenteral admin (solu-medrol) but can use orally
-no better than oral prednisone in acute asthma
minimal MC action
Triamcinolone
Potent systemic agent w/ excellent topical activity
NO MC activity
Dexamethosone
Most potent anti-inflammatory (activated)
used in adults (hydrocortisone in kids)
-used in cerebral edema, chemo-induced vomiting
Minimal MC action
greatest suppression of ACTH secretion @ pituitary.
