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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
Menotropins
purified FSH and LH extract
26
Gonadotropins clinical application
* **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
Gonadotropin AEs
* Women * **Ovarian hyperstimulation syndrome** * **Multiple pregnancies** (15-20%) * Headache, depression, edema, precocious puberty * Men * Gynecomastia
28
Gonadorelin = \_\_\_\_ Goserelin, Leuprolide, Nafarelin = \_\_\_\_ analogs are more ___ and \_\_-lasting
**GnRH**: Gonadorelin (4 min) **GnRH** **Analogs:** Goserelin, Leuprolide, Nafarelin (3 hrs) analogs are more **potent** and **longer**-lasting
29
\_\_\_\_ GnRH secretion is required to **stimulate** release of LH/FSH **Sustained nonpulsatile** admin. of GnRH **\_\_\_** FSH/LH release leading to \_\_\_\_
**Pulsatile** GnRH secretion is required to **stimulate** release of LH/FSH Sustained nonpulsatile admin. of GnRH **inhibits** FSH/LH release leading to **hypogonadism**
30
Continuous administration of GnRH hormone/analog gives ___ response: First 7 days = Chronic effects (\> 1 week) =
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
"-relin"/leuprolide **STIMULATION** effects
* **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
"-relin"/leuprolide more commonly used for **SUPPRESSING effects**
* **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
"-relin"/leuprolide more commonly used for **SUPPRESSING effects​** *(continued)*
* **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
GnRH **pulsatile** **treatment** AE's
* 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
GnRH **continuous** **treatment** AEs/contraindications
* **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
**"-relix"** Cetrorelix, Ganirelix
GnRH Receptor Antagonists
37
"-relix" clinical application
Suppress gonadotropin production​ **→ Prevent LH surge** during controlled ovarian hyperstimulation
38
**Corticotropin, Cosyntropin**
ACTH analogs
39
Corticotropin, Cosyntropin MOA
stimulate adrenal **cortex** via **MC2 receptor** (GPCR → increase cAMP) → secrete glucocorticoids, mineralocorticoids, androgen precursor
40
Corticotropin, Cosyntropin clinical application
* differentiate between **1°** **(Addison’s disease)** and **2°** **adrenal insufficiency** (inadequate ACTH secretion) * treat Infantile spasm **(West Syndrome)**
41
Corticotropin, Cosyntropin AEs
* 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
Describe Oxytocin
* 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
Oxytocin clinical application
* **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
Oxytocin AEs
* 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
oxytocin contraindications
* Fetal distress * Prematurity * Abnormal fetal presentation * Cephalopelvic disproportion * Uterine rupture predisposition
46
Atosiban
Oxytocin antagonist
47
Atosiban is used for treatment of ____ (not in USA)
Atosiban is used for treatment of **preterm labor** (not in USA)
48
Vasopressin, Desmopressin
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
ADH agonist clinical applications
* **Diabetes Insipidus DOC** * **Vasopressin:** Esophageal variceal bleeding & colonic diverticular bleeding * **Desmopressin:** Coagulopathy treatment in Hemophilia A and vWF disease
50
vasopressin agonist AEs
* Headache, nausea, abdominal cramps, allergic reactions * **Overdosage = hyponatremia & seizures**
51
Conivaptan use
* 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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