Pharm - Adrenal and Pituitary Dz Flashcards
Goal of treatment for Cushings syndrome
Normalize cortisol levels or action at its receptors to eliminate the signs and symptoms of CS
List 5 adjunct treatments for CS
- 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)
What are 8 cortisol-dependent comorbidities
- psych disorders
- DM
- HTN
- Hypokalemia
- Infectino
- Dyslipidemia
- Osteoporosis
- Poor physical fitness
What are risk factors for VTE i
- protein C and S
- factor 5 leiden
- stasis
- cancer
- trauma
- estrogen
What are the four categories of drug treatment for CS
- Steroidogenesis inhibitors
- Adrenolytic
- Glucocorticoid-receptor antagonists
- Somatostatin analogs
What are the three steroidogenesis inhibitors
- Metyrapone
- Ketoconazole
- Etomidate
What is the Adrenolytic agent
Mitotane (Lysodren)
What is the Glucocorticoid-receptor antagonists
Mifepristone (Korlym)
What is the Somatostatin analogs
Pasireotide (Signifor)
ID the major adverse effect of ketoconazole
Liver toxicity (reversible) is major adverse effect
What are the ketoconazole contraindications
acute or chronic liver disease
*do liver function tests before and after initiation of drug
What is the place in therapy for ketoconazole in CS?
agent of choice for long term use
ID the major adverse effect of metyrapone
- Androgen production increases (hirsutism in women)
- Not recommended as first-line for women requiring long term control, ok option if short term use only
What is the MoA of mitotane
- Destroys adrenocortical cells in zona fasciculate (glucocorticoids) and reticularis (androgens).
- Causes a medical adrenalectomy
What are 6 precautions realted to mitotane
- 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
MoA of mifepristone
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
Indicates for use of mifepristone
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
5 CI for mifepristone
- 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
Indicate for pasireotide
Tx of adults with Cushing dz in whom pituitary sx is not an option or has not been curative
What baseline tests should be run prior to the use of pasireotide? why?
- 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
What is the reason to provide steroid replacement in the treatment of adrenal adenoma?
Contralateral gland is usually atropic = decreased cortisol secretion
Goals of therapy for primary hyperaldosteronism
- Reversal of adverse CV effects
- Normalize serum potassium in hypokalemic patient
- Normalize blood pressure (often persists after correction of hyperaldosteronism)
What are three drugs used to treat primary hyperaldosteronism. What are the monitoring parameters for all three drugs?
- Spironolactone (Aldactone)
- Eplerenone (Inspra)
- Amiloride (Midamor)
Monitor serum Cr, K+, and blood pressure
What (overview) is the replacement therapy for Addison’s disease?
cortisol replacement
What are the cortisol replacement options for Addison’s disease?
- Short acting glucocorticoid: hydrocortisone
* Long acting glucocorticoid: dexamethasone and prednisone
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
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
What is the mineralocorticoid replacement therapy for Addison’s?
Fludrocortisone (Florinef)
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
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
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
What are three categories of meds to treat acromegaly and specific drugs for each category
- Somatostatin analog: Octreotide and Lanreotide
- Dopamine agonists: Cabergoline
- GH receptor antagonists: Pegvisomant
ADR and route of somatostatin analogs
- ADR: GI
- Route: SC or IM
ADR and Route of dopamine agonists
- ADR: nausea, light headed, mental fogginess
- Route: oral 1 x week (may be preferred due to oral route)
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
What four things might need replacement in a patient with panhypopituitarism
- cortisol
- TSH
- gonadotropins
- GH
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
What life situation influences gonadotropin replacement in pts with panhypopituitarism?
male vs. female
interest in fertility
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
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
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
goal of therapy when using desmopressin for DI
Decrease urine output, control polyuria and nocturia
mechanism of action of desmopressin
ADH/vasopressin analog: administration results in nonsuppressible ADH activity
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
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
Drugs of choice for nephrogenic DI
- HCTZ
- NSAIDs
