Pilch_AdrenalDrugs Flashcards
What is the administration method of GC and MC?
ALL ORALLY BIOAVAILABLE
Is there a natural form of GC? MC?
YES GC: Natural form of GC = Cortisol [hydrocortisone]
NO MC: Synthetic form of MC = FLUDROCORTISONE
What are the “CUSHINGOID EFFECTS” of GC?
- Glc metabolism - Hyperglycemia
- Fat metabolism - Central obesity (Moon facies, back hump, truncal obesity)
- Protein and bone metabolism - Catabolic (muscle wasting) + osteoporosis
- Immunosuppression - Opportunistic infection + Poor wound healing
- HTN
- Androgenic effects - Hirsutism + excessive sweating + acne
When does GC toxicity manifest itself as Cushingoid effects?
> 2 wks of therapy
What is the #1 most common opportunistic infection that pts taking GC therapy are most susceptible to? #2?
#1 = Candida albicans fungal infection #2 = Aspergillus fungal infection
Which prototypical GC has a short half-life, intermediate half-life, and long half-life?
SHORT: HYDROCORTISONE
INTERMEDIATE: PREDNISONE
LONG: DEXAMETHASONE
What is the classic replacement therapy of CHRONIC primary adrenocortical insufficiency?
GC (Hydrocortisone) + MC (Fludrocortisone)
*GC by itself is not enough to maintain BP
What are the 3 immediate steps of therapy for ACUTE primary adrenocortical insufficiency?
- LARGE PARENTERAL (IV) doses of HYDROCORTISONE - Oral dose won’t act quick enough since acute causes are life-threatening
- Fluid electrolyte abnormality correction
- Treat the underlying precipitating cause (e.g. infection, traum, hemorrahge)
When an ACUTE ADRENAL INSUFFICIENCY pt stabilizes, what is the regimen of treatment? What is the basis for this?
Ween the pt off of the HYDROCORTISONE because there could be SERIOUS WITHDRAWAL if hydrocortisone is cold-turkey stopped
What are 3 ways to assess the adequacy of corticosteroid replacement therapy?
2 Sx and 1 Hormone:
- HYPERPIGMENTATION resolution
- ELECTROLYTE resolution
- Plasma ACTH - Should NOT be suppressed, but should also be moderate levels
What is the main reason for testing AM ACTH levels in pts with corticosteroid therapy?
Mainly to prevent possible overtreatment
Overtreatment can cause SUPPRESSED ACTH
What is the most common mutated enzyme for CONGENITAL ADRENAL HYPERPLASIA? What is there a buildup of as a result?
21B-HYDROXYLASE (90% of pts) - Buildup of precursors that get shunted toward the ANDROGEN PATHWAY
What is the classic CP of CONGENITAL ADRENAL HYPERPLASIA in FEMALES, if not treated in utero with GC?
VIRILIZED EXTERNAL GENITALIA
What is the classic CP of CONGENITAL ADRENAL HYPERPLASIA in MALES, if not treated in utero with GC?
At birth: NORMAL
Later: Develop PRECOCIOUS PUBERTY
In pregnancies at high CAH risk, how can fetuses be protected from genital abnormalities?
ORAL ADMINISTRATION of DEXAMETHASONE to the mother -> Negative feedback to ACTH -> Reduces shunting + Massive surge of ACTH-mediated adrenal hyperplasia
What is the LONG-TERM REPLACEMENT therapy of pts with classical CAH? What is the basis for each?
GC (PREDNISONE) + MC (FLUDROCORTISONE)
- PREDNISONE = INTERMEDIATE ACTING GC (use this for alternate-day therapy to get GREATER ACTH suppression WITHOUT increasing growth inhibition) - Not too short (inadequate ACTH suppression), not too long (too much ACTH suppression)
- FLUDROCORTISONE - Also given because GC (cortisol) is insufficient by itself in maintaining BP
What is the GC potency and MC potency of DEXAMETHASONE? What is its half-life? What type of therapy is DEX mostly used for?
HIGH GC potency, barely any (0) MC potency
LONG half-life
Mostly used as treatments of pregnancies with HIGH RISK of CAH by oral administration to the mother
Why does GC dosage have to be carefully monitored for classical CAH?
Dosage needs to be adjusted to maintain normal growth and bone maturation
**Excess cortisol can reduce linear growth in children and cause osteoporosis
What is the most common cause of CUSHING SYNDROME?
EXOGENOUS CORTICOSTEROIDS
What is the most common cause of ENDOGENOUS Cushing syndrome?
CUSHING DISEASE - ACTH-secreting pituitary adenoma causing bilateral adrenal hyperplasia (BAH)
What is the treatment regimen of CUSHING SYNDROME due to exogenous corticosteroids?
Reduce dosage of GC GRADUALLY to prevent acute withdrawal Sx
How long does it take for the normal baseline function of the hypothalamic-pituitary adrenal axis to restore?
2-12mo for HPA axis to restore
Another 6-9mo for cortisol levels to normalize
What is the first-line treatment of CUSHING SYNDROME?
SURGICAL RESECTION OF TUMOR producing ACTH or cortisol
What are the Tx options if the tumor responsible for Cushing Syndrome is inoperable?
Radiotherapy
Bilateral adrenalectomy
Pharmacotherapy
What are the two types of drugs that can be used in the management of CUSHING SYNDROME/DISEASE to normalize CORTISOL production?
- ADRENAL BLOCKERS
2. ACTH ANTAGONISTS
What are the 2 specific types of ADRENAL BLOCKERS used for the Tx of CUSHING SYNDROME/DISEASE?
- BLOCK SYNTHESIS of adrenal steroids = KETOCONAZOLE
2. BLOCK GC RECEPTOR = MIFEPRISTONE (GC-R antagonist)
What are the 2 specific types of ACTH antagonists used for the Tx of CUSHING SYNDROME/DISEASE?
- DA-R AGONIST = CABERGOLINE
2. SOMASTOSTATIN (SST) AGONIST = PASIREOTIDE
At what level (hypothalamus, AP, or adrenal) do CABERGOLINE and PASIREOTIDE act at?
Level of the HYPOTHALAMUS (agonize DA and SST) that send inhibitory signals to PRL/TSH and GH/TSH, respectively
Which syndromes are these SOMATOTROPIN-R AGONISTS used for: OCTEOTRIDE, LANREOTIDE, and PASIREOTIDE?
OCTEOTRIDE and LANREOTIDE: GH-secreting ADENOMAS (e.g. GIGANTISM before epiphyses close in prepuberty children, ACROMEGALY after epiphyses close)
PASIREOTIDE: CUSHING SYNDROME/DISEASE
What is the most common cause of PRIMARY ALDOSTERONISM?
CONN SYNDROME =
ADRENAL ADENOMA hyper-secreting aldosterone
What are the pharmacotherapy Tx options of PRIMARY ALDOSTERONISM?
MINERALOCORTICOID RECEPTOR ANTAGONISTS = SPIRONOLACTONE + EPLERENONE
Can a pt with PRIMARY ALDOSTERONISM discontinue his/her SPIRONOLACTONE or EPLERENONE medication?
NO, NOT unless the adrenal adenoma tumor is resected bec HTN and HYPOKALEMIC states will return
Pt was initially on SPIRONOLACTONE, but switched to EPLERENONE bec he/she did not like the side effects associated with spironolactone. Describe the physiology of this occurrence.
SPIRONOLACTONE is great at inhibiting aldosterone, but has OFF-target side effects due to cross-reactivity with ANDROGEN/PROGESTERONE receptors -
EPLERENONE is MC-R specific and thus free of sex hormone side effects
What are some of the possible side effects of SPIRONOLACTONE?
Cross-reactivity with androgen and progesterone receptors -> GYNECOMASTIA, DECREASED LIBIDO, IMPOTENCE, IRREGULAR MENSES
What kind of tumor is a PHEOCHROMOCYTOMA? What does it secrete?
Neuroendocrine tumor of the ADRENAL MEDULLA derived from CHROMAFFIN cells
Secretes LOTS of NE/E
What are the clinical findings of PHEOCHROMOCYTOMA
HTN + Elevated HR + Palpitations
What is the standard protocol for treating a PHEOCHROMOCYTOMA? What does one need to be careful about particular with this Tx plan?
SURGICAL RESECTION of tumor BUT super important to stabilize BP and Pulse with medication prior to resection
Bec tumor is sensitive to touch -> Massive SURGE of NE/E -> Life-threatening
What is the main goal of pharmacotherapy associated with a PHEOCHROMOCYTOMA?
Keeping the BP and HR under control while the surgical resection is being conducted
What is the primary class of drug used prior to a PHEOCHROMOCYTOMA resection? What are the two other classes that may be used in the management?
- ALPHA-BLOCKERS**
- BETA-BLOCKERS (only after alpha-blockers) - pre-operative management
- CATECHOLAMINE BIOSYNTHESIS (Tyr Hydroxylase) INHIBITOR - management for pheo-associated HTN
Name the ALPHA BLOCKERS used for PHEOCHROMOCYTOMA pre-operative management.
-ZOSINS
PHENOXYBENZAMINE, DIBENZYLINE, PRAZOSIN, TERAZOSIN, DOXAZOSIN
Name the BETA BLOCKERS used for PHEOCHROMOCYTOMA pre-operative management.
ATENOLOL
METOPROLOL
PROPANOLOL
Name the catecholamine biosynthesis inhibitor used for management of PHEO-associated HTN
METYROSINE
