Pharm - Adrenal and Pituitary Dz Flashcards

(46 cards)

1
Q

Goal of treatment for Cushings syndrome

A

Normalize cortisol levels or action at its receptors to eliminate the signs and symptoms of CS

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2
Q

List 5 adjunct treatments for CS

A
  • Education to patient and family
  • Monitor for cortisol-dependent comorbidities
  • Evaluate pt for risk factors for VTE (10 fold risk of VTE with CS)
  • Perioperative prophylaxis for VTE
  • age appropriate vaccinations (influenza, herpes zoster, pneumocaccal)
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3
Q

What are 8 cortisol-dependent comorbidities

A
  • psych disorders
  • DM
  • HTN
  • Hypokalemia
  • Infectino
  • Dyslipidemia
  • Osteoporosis
  • Poor physical fitness
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4
Q

What are risk factors for VTE i

A
  • protein C and S
  • factor 5 leiden
  • stasis
  • cancer
  • trauma
  • estrogen
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5
Q

What are the four categories of drug treatment for CS

A
  1. Steroidogenesis inhibitors
  2. Adrenolytic
  3. Glucocorticoid-receptor antagonists
  4. Somatostatin analogs
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6
Q

What are the three steroidogenesis inhibitors

A
  • Metyrapone
  • Ketoconazole
  • Etomidate
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7
Q

What is the Adrenolytic agent

A

Mitotane (Lysodren)

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8
Q

What is the Glucocorticoid-receptor antagonists

A

Mifepristone (Korlym)

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9
Q

What is the Somatostatin analogs

A

Pasireotide (Signifor)

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10
Q

ID the major adverse effect of ketoconazole

A

Liver toxicity (reversible) is major adverse effect

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11
Q

What are the ketoconazole contraindications

A

acute or chronic liver disease

*do liver function tests before and after initiation of drug

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12
Q

What is the place in therapy for ketoconazole in CS?

A

agent of choice for long term use

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13
Q

ID the major adverse effect of metyrapone

A
  • Androgen production increases (hirsutism in women)

- Not recommended as first-line for women requiring long term control, ok option if short term use only

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14
Q

What is the MoA of mitotane

A
  • Destroys adrenocortical cells in zona fasciculate (glucocorticoids) and reticularis (androgens).
  • Causes a medical adrenalectomy
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15
Q

What are 6 precautions realted to mitotane

A
  • Discontinue immediately following shock or severe trauma and administer exogenous steroids
  • Adrenal insufficiency may develop requiring adrenal steroid replacement
  • Use caution in pts with liver dz or metastatic lesions of the adrenal cortex
  • Long term use of high dose may lead to brain damage
  • May prolong bleeding time, beware prior to sx or if co-administered with anticoagulants
  • Risk to fetus – advise women to use effective contraception
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16
Q

MoA of mifepristone

A

Cortisol receptor blockers – inhibit effect of cortisol at the glucocorticoid receptor at high doses. At low dose, is antiprogestational agent, competitively binds to intracellular progesterone receptor

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17
Q

Indicates for use of mifepristone

A

Controls hyperglycemia secondary to hypercortisolism in adult patients with endogenous Cushing syndrome who have T2DM or glucose intolerance and have failed or are not candidates for sx

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18
Q

5 CI for mifepristone

A
  • Pregnancy
  • Coadministration with simvastatin or lovastatin and CYP3A substrates that have a narrow therapeutic range
  • Pts who require systemic corticosteroids for serious medical conditions
  • Women with hx of unexplained vaginal bleeding
  • Women with endometrial hyperplasia with atypia or endometrial carcinoma
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19
Q

Indicate for pasireotide

A

Tx of adults with Cushing dz in whom pituitary sx is not an option or has not been curative

20
Q

What baseline tests should be run prior to the use of pasireotide? why?

A
  • Fasting plasma glucose and A1C: nearly all pts experience worsening glycemia at first, higher risk in poorly controlled DM
  • Liver tests
  • EKG, K+, mg+ : may cause bradycardia and QT prolongation
  • Gallbladder ultrasound: risk of cholelithiasis
  • TSH/FT4: pituitary hormone deficiency
  • GH/IGF-1: pituitary hormone deficiency
21
Q

What is the reason to provide steroid replacement in the treatment of adrenal adenoma?

A

Contralateral gland is usually atropic = decreased cortisol secretion

22
Q

Goals of therapy for primary hyperaldosteronism

A
  • Reversal of adverse CV effects
  • Normalize serum potassium in hypokalemic patient
  • Normalize blood pressure (often persists after correction of hyperaldosteronism)
23
Q

What are three drugs used to treat primary hyperaldosteronism. What are the monitoring parameters for all three drugs?

A
  1. Spironolactone (Aldactone)
  2. Eplerenone (Inspra)
  3. Amiloride (Midamor)
    Monitor serum Cr, K+, and blood pressure
24
Q

What (overview) is the replacement therapy for Addison’s disease?

A

cortisol replacement

25
What are the cortisol replacement options for Addison's disease?
* Short acting glucocorticoid: hydrocortisone | * Long acting glucocorticoid: dexamethasone and prednisone
26
Short acting glucocorticoid in the tx of Addison's: dosing information
Hydrocortisone • 10-12 mg/m2 (BSA) BID or TID • If dose BID, 2/3 AM and 1/3 afternoon
27
Long acting glucocorticoid in the tx of Addison's: dosing information
* Dexamethasone: 0.5 mg daily (PO) * Prednisone: 5 mg daily (PO) * Useful for those that are non-adherent with multiple daily dose schedules or those with severe late-evening or early morning symptoms that are not ameliorated by 2-3time daily hydrocortisone
28
What is the mineralocorticoid replacement therapy for Addison's?
Fludrocortisone (Florinef)
29
Dosing information for Fludrocortisone
• Usual PO dose is 0.1 mg/day • Lower dose (0.05 mg/day) may be possible if also taking hydrocortisone • Higher dose (0.2 mg/day) may be needed if also taking prednisone or dexamethasone • May need to increase dose in summer – salt loss due to perspiration **Liberal salt intake recommended, esp if exercising
30
When might a pt with Addison's disease need to increase glucocorticoid dose?
Illness – body needs more cortisol to deal with insult to body • Rule of 3X3: increase usual glucocorticoid dose 2-3X daily dose for 3 days Injury with substantial blood loss, fracture, nausea/vomiting and unable to retain oral meds, sx of acute adrenal insufficiency, pt is unresponsive: • Treat with injectable glucocorticoid
31
Indication for drug therapy in a pt with acromegaly
- Primary therapy: not a sx candidate, refuse sx, adenomas are unlikely to be cured surgically - Secondary therapy: surgery alone has not reduced serum GH and IGF-1 to normal
32
What are three categories of meds to treat acromegaly and specific drugs for each category
1. Somatostatin analog: Octreotide and Lanreotide 2. Dopamine agonists: Cabergoline 3. GH receptor antagonists: Pegvisomant
33
ADR and route of somatostatin analogs
- ADR: GI | - Route: SC or IM
34
ADR and Route of dopamine agonists
- ADR: nausea, light headed, mental fogginess | - Route: oral 1 x week (may be preferred due to oral route)
35
ADR and route for GH receptor antagonists
- ADR: injection site pain, NVD, flu-like sx, ALT/AST elevations - Route: SC daily injection •Current recommendations are to use this after failed to achieve normal IGF-1 serum concentrations on other agents
36
What four things might need replacement in a patient with panhypopituitarism
- cortisol - TSH - gonadotropins - GH
37
How is treatment with levothyroxine different in panhypopituitarism vs. primary hypopituitarism
• T4 should not be administered until adrenal function, including ACTH reserve, has been evaluated and either found normal or is treated • If pt has both hypothyroidism and hypoadrenalism, tx of hypothyroidism may increase clearance of the little bit of cortisol that is produced, increasing the severity of the cortisol deficiency. • Cannot use TSH to measure adequacy of T4 replacement. Instead, adjust T4 dose to maintain serum FT4 in upper half of reference range *factors that influence dosing are similar to primary hypopituitarism
38
What life situation influences gonadotropin replacement in pts with panhypopituitarism?
male vs. female | interest in fertility
39
Treatment of gonadotropins in male with panhypopituitarism
Not interested in fertility - Testosterone replacement Interested in fertility - Pituitary dz: LH/FSH - Hypothalamus dz: LH/FSH or GnRH
40
Treatment of gonadotropins in female with panhypopituitarism
Not interested in fertility - Estrogen-progestin replacement therapy: estradiol transdermal - If intact uterus, must also take progestin to avoid endometrial hyperplasia or carcinoma - Administer estradiol cyclically with progesterone or progestin to mimic normal cycle Interested in fertility - Ovulation induction - GnRH deficient = gonadotropin therapy or pulsatile GnRH - Pituitary dz: candidates for only gonadotropin therapy
41
What are the criteria for GH replacement therapy? (2)
- Low IGF-1 concentration or a poor GH response to at least two standard stimuli - Hypopituitarism due to pituitary or hypothalamic damage
42
goal of therapy when using desmopressin for DI
Decrease urine output, control polyuria and nocturia
43
mechanism of action of desmopressin
ADH/vasopressin analog: administration results in nonsuppressible ADH activity
44
what are the progressive goals of therapy when titrating the dose of desmopressin?
- Initial dose at bedtime can be titrated up or down depending on response of nocturia. - Additional daytime doses can be added if necessary
45
Describe the management and prevention of hyponatremia secondary to desmopressin
- Educate pts about sx induced by hyponatremia: nausea, vomiting, HA, lethargy, seizures and coma, mental status changes (Should call clinic at first signs of sx) - Give minimum dose required to control polyuria - Measure serum Na q 3-4 days during initial titration and then every 2-4 months. - Once stable dose is achieved, annual or biannual monitoring of serum Na is appropriate
46
Drugs of choice for nephrogenic DI
- HCTZ | - NSAIDs