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Pharmacology > Hypothalamic & Pituitary Hormones > Flashcards

Hypothalamic & Pituitary Hormones Flashcards

1
Q

GH / ____, predominantly required during ___

its effects are medated by ____

A

GH / somatotropin, predominantly required during childhood

its effects are medated by IGF-1

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2
Q

GH mediates effects via cell surface receptors that activate ____ signaling cascades

A

GH mediates effects via cell surface receptors that activate JAK/STAT signaling cascades

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3
Q

GH Physiological effects

A
  • Stimulation of longitudinal growth of bones
  • Increased bone mineral density
  • Increased muscle mass (in GH deficient people)
  • Increased GFR
  • Stimulation of preadipocyte differentiation into adipocytes
  • Anti-insulin actions (hyperglycemia) (decreased glucose utilization & increased lipolysis)
  • Development & increased function of immune system
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4
Q

GH deficiency

A
  • Genetic or damage to pituitary or hypothalamus
  • Short stature and adiposity (in children)
  • Hypoglycemia (unopposed insulin action)
  • Criteria for Dx
    • A growth rate < 4cm per year, and
    • the absence of a serum GH response to two GH secretagogues
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5
Q

Recombinant GH = ____

GH analog = ____

A

Recombinant GH = Somatropin

GH analog = Somatrem

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6
Q

Clinical use of Somatropin

A
  • Growth failure in children (turner XO, Prader Wili)
  • GH deficiency in adults
    • improves metabolic state, increased lean body mass, sense of well-being
  • Hasting in HIV+ pts
    • increased lean body mass, weight, physical endurance
  • Short bowel syndrome in pts receiving specialized nutrional support
    • ​improved GI function
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7
Q

Somatotropin/Somatrem AEs in children

A
  • Generally well tolerated
  • Scoliosis (during rapid growth)
  • Hypothyroidism
  • Intracranial hypertension (rare)
  • Otitis media (increased risk for Turner Syndrome patients)
  • Pancreatitis, gynecomastia & nevus growth
  • Diabetic syndrome (chronic use)
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8
Q

Somatotropin/Somatrem AEs in adults

A
  • Peripheral edema, myalgias & arthralgias (hands & wrists especially)
  • Carpal tunnel syndrome
  • Proliferative retinopathy (rare)
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9
Q

Somatotropin/Somatrem contraindications

A
  • Cytochrome P450 inducer
  • Patients with a known malignancy
    • can increase tumor growth
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10
Q

Small number of children with growth failure have ____deficiency

Analog of this?

A

Small number of children with growth failure have IGF-1 deficiency

Analog: Mecasermin

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11
Q

Mecasermin AEs

A
  • Hypoglycemia (eat 20 min before or after admin.)
  • Intracranial hypertension (rare)
  • Asymptomatic elevation of liver enzymes (rare)
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12
Q

Small GH-secreting adenomas can be treated with GH antagonists (3)

A
  • GH receptor antagonist → Pegvisomant
  • Somatostatin analogs → Octreotide
  • Dopamine receptor agonists → Bromocriptine, Cabergoline

(Larger pituitary adenomas require surgery or radiation)

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13
Q

JAK/STAT inhibitor

A

Pegvisomant (GH receptor antagonist)

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14
Q

describe the somatostain analog

A

Octreotide

t1/2: 30 x Somatostatin

(inhibits release of GH, TSH, glucagon, insulin, gastrin)

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15
Q

Octreotide clinical applications

A
  • Reduces symptoms from hormone-secreting tumors: acromegaly, carcinoid syndrome, gastrinoma, glucagonoma, nesidioblastosis, watery diarrhea, hypokalemia, achlorhydria syndrome & diabetic diarrhea.
  • Localizing neuroendocrine tumors
  • Controls bleeding from esophageal varices (vasoconstriction)
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16
Q

Octreotide AEs

A
  • Nausea, vomiting, abdominal cramps, flatulence, steatorrhea (with bulky bowel movements)
  • Constipation
  • Biliary sludge & gallstones (20-30% pts after 6mo use)
  • Sinus bradycardia (25%) & conduction disturbances (10%)
  • Vitamin B12 deficiency (long-term use)
  • Pain at injection site = common (esp. with long-acting)
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17
Q

Dopamine agonists

which drug has longer half-life?

A

Bromocriptine, Capergoline

Capergoline t1/2 ~65 h (preferred drug)

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18
Q

Bromocriptine, Capergoline Clinical use

A
  • Hyperprolactinemia
    • Standard treatment. Dopamine agonists shrink pituitary prolactin-secreting tumors, lower circulating prolactin levels, and restore ovulation in ~70% women with microadenomas & ~30% with macroadenomas
  • Acromegaly
    • Alone or in addition to surgery, radiation or octreotide admin
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19
Q

Bromocriptine, Capergoline AEs

A
  • Nausea (bromocriptine>cabergoline), headache, light- headedness, orthostatic hypotension, fatigue
  • Psychiatric manifestations
  • High doses = cold-induced peripheral digital vasospasm
  • Chronic high-dosage therapy = pulmonary infiltrates
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20
Q

Effects of Gonadotropins on females

A

FSH: ovarian follicle development

FSH & LH: ovarian steroidogenesis

Luteal stage of menstrual cycle: estrogen & progesterone production is primarily under control of LH. During pregnancy hCG takes over.

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21
Q

Effects of Gonadotropins on males

A

FSH: Spermatogenesis, conversion of testosterone to estrogen. Maintains high local androgen concentrations in vicinity of developing cells

LH: Stimulates testosterone production

22
Q

clinical application of gonadotropins

A

Infertility

  • induce spermatogenesis (men)
  • induce ovulation (women)
23
Q

Follitropin and Urofollitropin

A

Purified FSH

24
Q

Lutropin alfa

A

Recombinant LH

25
Q

Menotropins

A

purified FSH and LH extract

26
Q

Gonadotropins clinical application

A
  • Male Infertility
    • d/t hypogonadism, requires both FSH and LH
  • Induce Ovulation
    • Expensive and complicated so reserved for when other treatments don’t work
27
Q

Gonadotropin AEs

A
  • Women
    • Ovarian hyperstimulation syndrome
    • Multiple pregnancies (15-20%)
    • Headache, depression, edema, precocious puberty
  • Men
    • Gynecomastia
28
Q

Gonadorelin = ____

Goserelin, Leuprolide, Nafarelin = ____

analogs are more ___ and __-lasting

A

GnRH: Gonadorelin (4 min)

GnRH Analogs: Goserelin, Leuprolide, Nafarelin (3 hrs)

analogs are more potent and longer-lasting

29
Q

____ GnRH secretion is required to stimulate release of LH/FSH

Sustained nonpulsatile admin. of GnRH ___ FSH/LH release leading to ____

A

Pulsatile GnRH secretion is required to stimulate release of LH/FSH

Sustained nonpulsatile admin. of GnRH inhibits FSH/LH release leading to hypogonadism

30
Q

Continuous administration of GnRH hormone/analog gives ___ response:

First 7 days =

Chronic effects (> 1 week) =

A

Continuous administration of GnRH hormone/analog gives biphasic response:

First 7 days = agonist response ‘flare’

Chronic effects (> 1 week) = inhibitory action (receptor down-regulation & changes in signaling pathways)

31
Q

“-relin”/leuprolide STIMULATION effects

A
  • Male infertility
    • d/t hypothalamic hypogonadotropic hypogonadism (pulsatile gonadorelin)
  • Dx LH responsiveness in delayed puberty
    • whether it is d/t constitutional delay or hypogonadotropic hypogonadism
  • Female infertility: uncommon (inconvenient & costly)
32
Q

“-relin”/leuprolide more commonly used for SUPPRESSING effects

A
  • Controlled ovarian hyperstimulation
    • ​leuprolide, nafarelin
    • ​suppress LH surge that can prematurely trigger ovulation
  • Endometriosis
    • ​leuprolide, Goserelin, Nafarelin
    • ​decreased pain
  • Uterine Leiomyomata/fibroids
    • ​Leuprolide, Goserelin, Nafarelin
    • reduce fibroid size
  • Prostate Cancer
    • Leuprolide, Goserelin
    • ​continuous GnRH Agonist and androgen receptor antagonist = effective as castration in reducing serum testosterone
33
Q

“-relin”/leuprolide more commonly used for SUPPRESSING effects​ (continued)

A
  • Central Precocious Puberty
    • leuprolide, nafarelin
  • Advanced Breast & Ovarian Cancer
  • Treatment of Amenorrhea & Infertility in women with Polycystic Ovary Disease
  • Thinning of Endometrial lining
    • ​Preparation for endometrial ablation procedure in women with dysfunctional uterine bleeding
34
Q

GnRH pulsatile treatment AE’s

A
  • Headache, light-headedness, nausea, flushing
  • Swelling at SC injection site
  • HSN dermatitis (long-term admin.)
  • acute HSN reactions
  • Sudden pituitary apoplexy & blindness (in pts with gonadotropin-secreting pituitary tumor)
35
Q

GnRH continuous treatment AEs/contraindications

A
  • Women:
    • Menopausal sxs, depression, diminished libido, generalized pain, vaginal dryness & breast atrophy
    • Ovarian cysts (generally resolve)
    • Reduced bone density & osteoporosis (long treatment)
  • Men: Hot flushes, sweats, edema, gynecomastia, decreased libido, decreased hematocrit, reduced bone density, asthenia, & injection site reactions
  • Contraindicated: Pregnant or Breast-feeding
36
Q

“-relix”

Cetrorelix, Ganirelix

A

GnRH Receptor Antagonists

37
Q

“-relix” clinical application

A

Suppress gonadotropin production​ → Prevent LH surge during controlled ovarian hyperstimulation

38
Q

Corticotropin, Cosyntropin

A

ACTH analogs

39
Q

Corticotropin, Cosyntropin MOA

A

stimulate adrenal cortex via MC2 receptor (GPCR → increase cAMP) →
secrete glucocorticoids, mineralocorticoids, androgen precursor

40
Q

Corticotropin, Cosyntropin clinical application

A
  • differentiate between 1° (Addison’s disease) and 2° adrenal insufficiency (inadequate ACTH secretion)
  • treat Infantile spasm (West Syndrome)
41
Q

Corticotropin, Cosyntropin AEs

A
  • simiar to Glucocorticoids
  • short term: HTN, hyperglycemia, immunosuppression, psychotic rxns, cognitive impairment
  • long term: osteoporosis, weight gain, edema, poor wound healing, ulcers, adrenal suppression
42
Q

Describe Oxytocin

A
  • Acts on GPCRs → stimulates release of PGs & LTs that augment uterine contraction
  • Small dose: increase force & frequency of contractions
  • High dose (not good): sustained contractions. Weak antidiuretic & pressor activity (vasopressin R activation)
  • Contraction of myoepithelial cells surrounding mammary alveoli → milk ejection
43
Q

Oxytocin clinical application

A
  • Labor Induction: When early vaginal delivery is required (Rh problems, maternal diabetes, preeclampsia, ruptured membranes)
  • Augment Normal Labor: When labor is protracted or displays arrest disorder
  • Control of uterine hemorrhage
44
Q

Oxytocin AEs

A
  • Severe toxicity is rare
  • Excess stimulation of uterine contractions
    • ​Fetal distress, placental abruption, uterine rupture
  • Inadvertent activation of vasopressin receptors
    • ​Excess fluid retention, water intoxication → hyponatremia, heart failure, seizures, death
  • Bolus injections can lead to hypotension
    • ​Administer IV as dilute solution at a controlled rate
45
Q

oxytocin contraindications

A
  • Fetal distress
  • Prematurity
  • Abnormal fetal presentation
  • Cephalopelvic disproportion
  • Uterine rupture predisposition
46
Q

Atosiban

A

Oxytocin antagonist

47
Q

Atosiban is used for treatment of ____ (not in USA)

A

Atosiban is used for treatment of preterm labor (not in USA)

48
Q

Vasopressin, Desmopressin

A

ADH agonists

  • Vasopressin
    • released in response to rising plasma tonicity or falling BP
    • both antidiuretic and vasopressor activities
  • Desmopressin
    • long acting
    • minimal V1 action (vascular smooth muscle)
    • antidiuretic to vasopressor ratio 4000 x vasopressin
49
Q

ADH agonist clinical applications

A
  • Diabetes Insipidus DOC
  • Vasopressin: Esophageal variceal bleeding & colonic diverticular bleeding
  • Desmopressin: Coagulopathy treatment in Hemophilia A and vWF disease
50
Q

vasopressin agonist AEs

A
  • Headache, nausea, abdominal cramps, allergic reactions
  • Overdosage = hyponatremia & seizures
51
Q

Conivaptan use

A
  • Vasopressin antagonist
  • used for pts w/ hyponatremia d/t elevated ADH (SIADH)
  • high affinity for V1 and V2

Pharmacology (19 decks)

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