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Pharm: Endocrine and Derm > Hypothalamus, Pituitary, and Thyroid Meds > Flashcards

Hypothalamus, Pituitary, and Thyroid Meds Flashcards

1
Q

Clinical Uses of Gonadotropin Replacement

A

Controlled ovarian stimulation

Induced follicle development and ovulation

Stimulate spermatogenesis in men

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2
Q

LH & FSH replacement Drug and MOA

A

Menotropins (hMG) (Menopur ®; Repronex ®)

actions occur as a result of both FSH and LH

In females: timulates the development and maturation of the ovarian follicle (FSH), cause ovulation (LH), and stimulate the development of the corpus luteum (LH)
In males: it stimulates spermatogenesis (LH)

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3
Q

FSH Replacement Drug

A

Follitropin alfa (Gonal-f ®); beta (Follistim®)

Urofollitropin (uFSH) (Bravelle ®)

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4
Q

LH Replacement Drug

A

Lutropin alfa (Luveris ®)

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5
Q

hCG Replacement Drug

A

Choriogonadotropin alfa (rhCG)

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6
Q

Uses of Menotropins in Females with HCG

A

Induce ovulation in patients with functional oligoanovulation or anovulation

Stimulation of multiple follicle development in ovulatory patients as part of an assisted reproductive technology (ART)

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7
Q

Uses of Menotropins in Males (off-label)

A

Stimulation of spermatogenesis in primary or secondary hypogonadotropic hypogonadism

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8
Q

Use of Urofollitropin (Bravelle) and MOA

A

Highly purified human FSH extracted from the urine of postmenopausal women

LH activity is removed

Stimulates ovarian follicular growth in women who do not have primary ovarian failure.

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9
Q

Follitropin alfa (Gonal-f ®) and Follitropin beta (Follistim®) Uses and MOA

A

Recombinant FSH; identical to human FSH

Shorter half-life but equal or more efficient estrogen secretion

Stimulate ovarian follicular growth in women who do not have primary ovarian failure, and stimulate spermatogenesis in men with hypogonadotrophic hypogonadism

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10
Q

Lutropin Alfa (Luveris) Use and MOA

A

Recombinant LH

Administration leads to increased follicular estradiol secretion needed for follicle stimulating hormone induced follicular development

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11
Q

Choriogonadotropin alfa (rhCG) Use and MOA

A

Induces ovulation and pregnancy in anovulatory, infertile females; treatment of hypogonadotropic hypogonadism, prepubertal cryptorchidism; spermatogenesis induction with follitropin alfa

Stimulates production of gonadal steroid hormones by causing production of androgen by testes; as a substitute for LH to stimulate ovulation

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12
Q

Gonadtropins ADE

A

HA, depression, edema, precocious puberty, hCG antibody production (rare)
Commonly Reversible, uncomplicated ovarian enlargement
Gynecomastia in men

Serious: Multiple pregnancies,
Increased risk of gestational diabetes, preeclampsia, preterm labor.
Ovarian hyperstimulation syndrome (OHSS)
0.5-4%
Ovarian enlargement, ascites, hydrothorax, hypovolemia, fever, arterial thromboembolism, sometimes resulting in shock – can be fatal

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13
Q

GnRH Agonist Names

A 
Gonadorelin
Goserelin
Histrelin
Leuprolide
Nafarelin
Triptorelin
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14
Q

GnRH Agonists MOA

A

Regulates FSH, LH release from anterior pituitary:
Pulsatile release stimulates FSH, LH release; promotes ovulation
or
Continuous (non-pulsatile) release inhibits FSH, LH release; used to treat hormone sensitive cancers

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15
Q

GnRH Agonist Pulsatile Stimulation Use and Administration

A

Female infertility:
Induces LH surge in women undergoing ovulation induction with gonadotropins
Portable IV pump delivers pulse every 90 minutes
Less likely to cause multiple pregnancies

Male infertility:
IV as above
Regular serum testosterone levels, semen analyses needed

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16
Q

GnRH Agonist Continuous Suppression Use

A

Prostate cancer:
GnRH and a androgen receptor antagonist reduces serum testosterone
Reach hypogonadal levels within 2 weeks

Blocks LH surge that could prematurely trigger ovulation during controlled ovarian hyperstimulation in IVF protocols

Endometriosis:
Estrogen-sensitive endometrium-like tissue outside the uterus
Blocks cyclical changes in estrogen/progesterone resulting in abdominal pain

Uterine benign fibroids:
Estrogen-sensitive fibroids cause menorrhagia with associated anemia and pelvic pain

Central precocious puberty:
Onset of secondary sex characteristics before age 8 in girls, age 9 in boys

Other uses:
Advanced ovarian and breast cancer, thinning of endometrial lining, amenorrhea and infertility in women with PCOS

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17
Q

Why is Endotmetriosis GnRH agonist treatment limited to 6 months?

A

Treatment beyond this length of time can result in reduced bone density

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18
Q

GnRH Antagonist Uses

A

Suppression of gonadotropin production:
Prevents LH surge which may trigger early egg release

Advanced prostate cancer:
Abarelix
When GnRH agonist not tolerated
Avoids testosterone surge seen with GnRH agonist

Usually well tolerated

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19
Q

GnRH Antagonist MOA and drugs

A

Inhibits FSH and LH release

Available agents: Ganirelix, cetrotelix, abarelix, degarelix

20
Q

Hypoprolactinemia Replacement Drugs

A

Replacement drugs unavailable

21
Q

Hyperprolactinemia Drug MOA

A

PRL release inhibited by dopamine agonists

Dopamine (DA) D2 receptor agonists stimulate the DA receptor -> replace endogenous DA -> inhibits PRL release from the anterior pituitary

22
Q

Hyperprolactinemia Drugs

A

Bromocriptine (Parlodel ®), cabergoline (Dostinex ®) - these are Dopamine agonists

23
Q

Dopamine Agonists ADE

A

Common: nausea, HA, dizziness, orthostatic hypotension, fatigue
(Cabergoline and/or vaginal administration less nausea)

Psychiatric manifestations: nervousness/anxiert

Pulmonary infiltrates and fibrosis with chronic high-dose

24
Q

GH Replacement Drugs

A

Nine GH products in the US, we focused on:
Somatrem (Protropin ®)
Somatropin

25
GH Toxicity
Generally well tolerated | Hyperthyroidism, pancreatitis, gynecomastia
26
GH Contraindications
Adults (DO NOT USE ONCE GROWTH PLATES HAVE CLOSED) Known Malignancy May increase mortality in critically ill patients
27
Treatment for growth retardation resistant to GH
IGF-1 (Mecasermin), approved for IGF-1 deficiency not responsive to recombinant GH
28
IGF-1 Replacement ADE
Most common: hypoglycemia – administer 20 minutes after snack or meal Intracranial hypertension Asymptomatic liver enzyme elevation
29
IGF-1 must be administered with what?
IGFBP, because IGF-1 and IGFBP-1 release are stimulated by GH
30
GH Overproduction 1st Line Treatment
1st Line treatment: transsphenoidal surgical resection of the GH-secreting adenoma. Octreotide (synthetic somatostatin analogue) given prior to surgery to reduce tumor size (Cure rate 50-90%)
31
GH Overproduction 2nd Line Treatment
2nd Line: Radiation therapy poor surgical candidates and non-responders to previous surgery Delayed therapeutic effects
32
GH Overproduction 3rd Line Treatment Should be Used when?
Symptomatic control Indication with meds if surgery and irradiation are contraindicated Rapid control of symptoms needed Treatment failure with other agents to normalize GH and IGF-1 concentrations
33
GH reduction meds
Somatostatin analogs: Octreotide (Sandostatin ®) Lantreotide (Somatuline ®) Dopamine receptor agonists: Bromocriptine (Cycloset ®; Parlodel ®) Cabergoline Lisuride (Last Resort Drug) GH receptor antagonist: Pegvisomant (Somavert)
34
Somatostatin Analogue MOA
Octreotide (Sandostatin ®) and Lantreotide (Somatuline ®) Long acting analog 45x more potent than somatostatin at inhibiting GH release Suppresses [GH] < 5 mcg/L and normalizes [IGF-1] in 50-60% of acromegaly patients Only 2x as potent in reducing insulin secretion Hyperglycemias rare
35
Somatostatin Analogues Indications
Reduces symptoms due to hormone secreting tumors Bleeding from esophageal varices Radiolabeled octreotide to localize neuroendocrine tumors with somatostatin receptors (May aid to predict response to octreotide therapy) Lantreotide (Somatuline ®)- approved to treat acromegaly butmed not commonly used.
36
Somatostatin Analogues ADE
GI (most common): N/V, abdominal cramps, flatulence, steatorrhea (fatty stools), malabsortion of fat Sinus Bradycardia (25%) Biliary sludging Gall stones in 20-30% after 6 months (1% yearly incidence) Endocrine system: hypothyroidism, abnormalities in glucose metabolism (keep an eye on blood sugar)
37
GH Receptor Antagonists ADE
Generally well-tolerated Injection-site pain, nausea, diarrhea, and flu-like symptoms Significant but reversible LFT elevations (<1%)
38
Oxytocin (Pitocin ®) Uses
Labor induction and augmentation Postpartum uterine bleeding
39
Oxytocin (Pitocin ®) ADE
Rare with judicious use Excessive uterine contractions - Fetal distress, placental abruption, uterine rupture - Maternal and fetal monitoring can detect early Vasopressin receptor activation - Fluid retention/water intoxication - Hyponatremia, heart failure, seizures, death (due to the seizures and hyponatremia)
40
Oxytocin (Pitocin ®) Contraindications
Fetal distress, abnormal fetal presentation or other predispositions to uterine rupture
41
Vasopressin Analog Drug and Pharmacokinetics
Desmopressin (DDAVP; Stimate ®) ``` Minimal V1 (vasoconstriction and BP elevation) activity. 4000x greater antidiuretic effect compared to ADH ``` Long-acting Half-life: 1.5-2.5 hours (ADH = 15 min) Multiple dosage formulations Oral, IV, SC, intranasal
42
Vasopressin Uses
Pituitary diabetes insipidus (ADH deficiency treatment of choice)- reduces polyuria, polydipsia, hypernatremia Nocturnal bedwetting (MC, in her experience) Given IV ->Treat bleeding due to: Esophageal variceal Conlonic diverticula Coagulopathies: Hemophillia A and von Willebrand’s disease
43
Vasopressin ADE
Rare: HA, nausea, abdominal cramps, agitation, allergic reactions Hyponatremia, seizures in overdose Vasoconstriction -use caution in coronary artery disease (CAD) DDAVP nasal insufflation less effective in nasal congestion, otherwise this form is pretty harmless
44
Vasopressin Antagonist Drugs and Use:
Therapeutic agents available: Conivaptan (Vaprisol ®) Effects on V1a and V2 receptors Tolvaptan (Samsca ®) V2 > V1 USE: Treatment of hyponatremia (not a drug for first choice for this b/c could use a cheap hypertonic solution), acute heart failure
45
Vasopressin Receptor Effects
V1  Vasoconstriction and blood pressure elevation V2 Renal -> Reduced diuresis (water retention) V2 Extra Renal -> Regulate coagulation factor VIII, von Willebrand factor

Pharm: Endocrine and Derm (6 decks)

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