2/10 Hypothal Pit Pharm - Pilch

Question 1

hypothalamic-pituitary endocrine system

Answer 1

hypothalamic factors → regulate release of anterior pituitary hormones

anterior pit hormones (except prolactin) → stim hormonal production in endocrine gland, liver, bone, tissues

post pit hormones → act directely on target tissues

Question 2

GROWTH HORMONE

Answer 2

req during childhood, adolescence for attainment of normal adult size

growth-promoting effect mediated mainly by IGF1

• bone growth → linear height
• anabolic effects in muscle → incr muscle mass
• catabolic effects in lipid cells → decr adiposity
• induces insulin resistance

tx: recombinanty human GH/rhGH (Somatropin, Somatotropin)

Question 3

growth hormone deficiency

Answer 3

children: short stature
adults: generalized obesity, reduced muscle mass, asthenia, reduced cardiac output

tx with rhGH → reversal of manifestations

• can also be used to treat conds assoc with short stature that are NOT caused by GH def
• tox_children: psudotumor cerebri, progression of scoliosis, edema, hyperglycemia
  
  • check for def in other ant pit hormones requiring tx
• tox_adults: periph edema, myalgias, arthralgias (hands/wrists) remit with dose reduction
  
  • carpal tunnel

Question 4

mecasermin

Answer 4

rh IGF1

good for severe IGF1 deficiency

tox: hypoglycemia (poss due to potnetiation of action of insulin via activation of insulin receptor)

Question 5

GH antagonists

what conds?

two types and examples

Answer 5

GH producing cells in ant pit can form GH-secreting adenomas → acromegaly

somatostatin analogs

OCTREOTIDE

• n/v, abd cramps, flatulence, gallstones, sinus bradycardia, conduction issues

LANREOTIDE

GH receptor antagonist

PEGVISOMANT

Question 6

GONADOTROPINS

Answer 6

complementary fx in reproductive process

• used in states of infertility to stimulate spermatogenesis induce ovulation
• most common use: controlled ovarian hyperstim (COH) in assisted repro procedures like IVF

FSH (follicle stim hormone)

• three purified forms available
  
  1. urofollitropin (uFSH) : from urine of postmenopausal women
  2. follitropin alpha, follitropin beta : recombo FSH (rFSH) w short halflife

LH (luteinizing hormone)

1. lutropin alpha : recombo LH (rLH) approved for use only in combo with follitropin alpha → stim follicular devpt in infertile women with LH def

hCG (human chorionic gonadotropin)

• produced by placenta, excreted into urine
• two forms available:

1. extracted/purified from urine
2. chriogonadotropin alpha : recombo hCG (rHCG)

Question 7

gonadotropins

toxicities/complications

Answer 7

women tx with gonadotropins, hCG

two serious complications:

1. ovarian hyperstimulation syndrome (OHSS)
   
   • ovarian enlargement, ascites, hydrothorax, hypovolemia → shock
2. multiple pregnancies

Question 8

GnRH agonists

mechanism

examples

usage x4

Answer 8

mechanism

• pulsatile secretion of GnRH from hypothal stimulates production and release of ant pit gonadotropins (FSH, LH)
• sustained NON-pulsatile admin of GnRH or GnRH agonists inhibits pit release of FSH, LH

gonadorelin (acetate salt of human GnRH)

goserelin, histrelin, leuprolide, nafarelin, triptorelin (synthetic GnRH agonists)

clinical application

1. endometriosis: cyclical abd pain in premenopausal women due to estrogen-sensitive endometrium-like tissue outside uterus
   
   • reduced by abolishing exposure to cyclical changes in estrogen/progesterone that occur during menses
   • tx with continuous GnRH agonist → reduced estrogen/progesterone levels, prevents cyclical changes
   • leuprolide, goerelin, nararelin
2. ​uterine leiomyomata (fibroids): benign, estrogen-sensitive, fibrous growths in uterus → menorrhagia, anemia, pelvic pain
   
   • tx 3-6mo with continuous GnRH agonist → reduce fibroid size + (combo with Fe) improve anemia
   • leuprolide, goserelin, nafarelin
3. ​​prostate cancer
   
   • ​combo tx with continuous GnRH agonist and androgen receptor antagonist (flutamide, bicalutamide) → reduces serum testosterone levels/effects
     
     • knocks down both pit/testes testosterone AND adrenal androgens
   • leuprolide, goserelin, histrelin, triptorelin
4. ​central precocious puberty: onset of secondary sex chars before 7-8yo girls, 9yo boys
   
   • tx: cont GnRH agonist for tx of GnRH-dep CPP if:
     
     • ​child’s final height would be signif compromised
     • child in signif emotional distress due to devpt of pubertal secondary sex chars
   • ​​leuprolide, annual implant of histrellin (until 11 in females, 12 in males)​

Question 9

GnRH agonist toxicities

Answer 9

continuous tx?

• WOMEN
  
  • sx of MENOPAUSE
    
    • hot flashes, sweats, headaches
  • depression, diminished libido, generalized pain, vag dryness, breast atrophy
  • ovarian cysts within 2mo, usually resolve after 6wk
  • osteoporosis with prolonged use
    
    • need to monitor bone density
• MEN
  
  • hot flashes, edema, gynecomastia, decr libido, decr hematocrit, reduced bone density, asthenia

Question 10

GnRH receptor antagonists

Answer 10

(-elix)

mech: inhibit secretion of FSH and LH in dose-dep and more complete manner than GnRH agonists

• ganirelix, cetorelix : controlled ovarian hyperstim procedures (lower risk of OHSS)
• degarelix : symptomatic adv prostate cancer
  
  • → signs and sx of androgen deprivation (hot flashes, edema)

Question 11

dopamine agonists

Answer 11

standard pharm tx for hyperprolactinemia: elevated serum PRL commonly caused by presence of PRL-secreting adenoma

• women: amenorrhea, galactorrhea
• men: loss of libido, fertility

tx: bromocriptine, cabergoline (ergot deriv w high affinity for D2 receptors)

• shrink pituitary PRL tumors, lower circulating PRL levels, restore ovulation in 70%_F_microadenoma, 30%_F_macroadenoma

tox: nausea, headache, light-headedness, orthostatic hypoTN, fatigue, possible psych manifestations

• cabergoline has fewer side effects than bronocriptine BUT assoc with cardiac valvulopathy

Question 12

oxytocin

Answer 12

oxytocin is a post pit hormone imp for labor/delivery (incr freq and force of uterine contractions), milk ejection in lactation

synthetic oxytocin

• induction of labor for early vag delivery (uncontroled mat diabetes, worsening preeclampsia, intrauterine inf)
• postpartum: controlling uterine hemorrhage due to uterine atony

tox:

• excessive stim of uterine contractions → fetal distress, placental abruption, uterine rupture
• inadvertent activation of ADH receptors → fluid retention, water intox → hyponatremia, heart failure, seizures

contraindications: fetal distress, abnormal fetal presentation, cephalopelvic disproportion, predisp for uterine rupture