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

Hypothalamus, Pituitary, and Thyroid Meds Flashcards

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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
Q

GH Toxicity

A

Generally well tolerated

Hyperthyroidism, pancreatitis, gynecomastia

26
Q

GH Contraindications

A

Adults (DO NOT USE ONCE GROWTH PLATES HAVE CLOSED)

Known Malignancy

May increase mortality in critically ill patients

27
Q

Treatment for growth retardation resistant to GH

A

IGF-1 (Mecasermin), approved for IGF-1 deficiency not responsive to recombinant GH

28
Q

IGF-1 Replacement ADE

A

Most common: hypoglycemia – administer 20 minutes after snack or meal

Intracranial hypertension

Asymptomatic liver enzyme elevation

29
Q

IGF-1 must be administered with what?

A

IGFBP, because IGF-1 and IGFBP-1 release are stimulated by GH

30
Q

GH Overproduction 1st Line Treatment

A

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
Q

GH Overproduction 2nd Line Treatment

A

2nd Line: Radiation therapy
poor surgical candidates and non-responders to previous surgery
Delayed therapeutic effects

32
Q

GH Overproduction 3rd Line Treatment Should be Used when?

A

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
Q

GH reduction meds

A

Somatostatin analogs:
Octreotide (Sandostatin ®)
Lantreotide (Somatuline ®)

Dopamine receptor agonists:
Bromocriptine (Cycloset ®; Parlodel ®)
Cabergoline
Lisuride

(Last Resort Drug) GH receptor antagonist: Pegvisomant (Somavert)

34
Q

Somatostatin Analogue MOA

A

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
Q

Somatostatin Analogues Indications

A

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
Q

Somatostatin Analogues ADE

A

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
Q

GH Receptor Antagonists ADE

A

Generally well-tolerated

Injection-site pain, nausea, diarrhea, and flu-like symptoms

Significant but reversible LFT elevations (<1%)

38
Q

Oxytocin (Pitocin ®) Uses

A

Labor induction and augmentation

Postpartum uterine bleeding

39
Q

Oxytocin (Pitocin ®) ADE

A

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
Q

Oxytocin (Pitocin ®) Contraindications

A

Fetal distress, abnormal fetal presentation or other predispositions to uterine rupture

41
Q

Vasopressin Analog Drug and Pharmacokinetics

A

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
Q

Vasopressin Uses

A

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
Q

Vasopressin ADE

A

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
Q

Vasopressin Antagonist Drugs and Use:

A

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
Q

Vasopressin Receptor Effects

A

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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