Hypothalamus, Pituitary, and Thyroid Meds Flashcards
Clinical Uses of Gonadotropin Replacement
Controlled ovarian stimulation
Induced follicle development and ovulation
Stimulate spermatogenesis in men
LH & FSH replacement Drug and MOA
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)
FSH Replacement Drug
Follitropin alfa (Gonal-f ®); beta (Follistim®)
Urofollitropin (uFSH) (Bravelle ®)
LH Replacement Drug
Lutropin alfa (Luveris ®)
hCG Replacement Drug
Choriogonadotropin alfa (rhCG)
Uses of Menotropins in Females with HCG
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)
Uses of Menotropins in Males (off-label)
Stimulation of spermatogenesis in primary or secondary hypogonadotropic hypogonadism
Use of Urofollitropin (Bravelle) and MOA
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.
Follitropin alfa (Gonal-f ®) and Follitropin beta (Follistim®) Uses and MOA
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
Lutropin Alfa (Luveris) Use and MOA
Recombinant LH
Administration leads to increased follicular estradiol secretion needed for follicle stimulating hormone induced follicular development
Choriogonadotropin alfa (rhCG) Use and MOA
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
Gonadtropins ADE
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
GnRH Agonist Names
Gonadorelin Goserelin Histrelin Leuprolide Nafarelin Triptorelin
GnRH Agonists MOA
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
GnRH Agonist Pulsatile Stimulation Use and Administration
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
GnRH Agonist Continuous Suppression Use
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
Why is Endotmetriosis GnRH agonist treatment limited to 6 months?
Treatment beyond this length of time can result in reduced bone density
GnRH Antagonist Uses
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
GnRH Antagonist MOA and drugs
Inhibits FSH and LH release
Available agents: Ganirelix, cetrotelix, abarelix, degarelix
Hypoprolactinemia Replacement Drugs
Replacement drugs unavailable
Hyperprolactinemia Drug MOA
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
Hyperprolactinemia Drugs
Bromocriptine (Parlodel ®), cabergoline (Dostinex ®) - these are Dopamine agonists
Dopamine Agonists ADE
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
GH Replacement Drugs
Nine GH products in the US, we focused on:
Somatrem (Protropin ®)
Somatropin
GH Toxicity
Generally well tolerated
Hyperthyroidism, pancreatitis, gynecomastia
GH Contraindications
Adults (DO NOT USE ONCE GROWTH PLATES HAVE CLOSED)
Known Malignancy
May increase mortality in critically ill patients
Treatment for growth retardation resistant to GH
IGF-1 (Mecasermin), approved for IGF-1 deficiency not responsive to recombinant GH
IGF-1 Replacement ADE
Most common: hypoglycemia – administer 20 minutes after snack or meal
Intracranial hypertension
Asymptomatic liver enzyme elevation
IGF-1 must be administered with what?
IGFBP, because IGF-1 and IGFBP-1 release are stimulated by GH
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%)
GH Overproduction 2nd Line Treatment
2nd Line: Radiation therapy
poor surgical candidates and non-responders to previous surgery
Delayed therapeutic effects
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
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)
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
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.
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)
GH Receptor Antagonists ADE
Generally well-tolerated
Injection-site pain, nausea, diarrhea, and flu-like symptoms
Significant but reversible LFT elevations (<1%)
Oxytocin (Pitocin ®) Uses
Labor induction and augmentation
Postpartum uterine bleeding
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)
Oxytocin (Pitocin ®) Contraindications
Fetal distress, abnormal fetal presentation or other predispositions to uterine rupture
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
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
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
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
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
