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CAS 3 > Drugs for hypothalamic and pituitary disorders > Flashcards

Drugs for hypothalamic and pituitary disorders Flashcards

1
Q

what are the cell cycle receptors for GH and PRL?

A

JAK/STAT

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2
Q

which hormones have GPCR receptors?

A

all except GH and PRL

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3
Q

GnRH in pulses –>promote

A

LH, FSH,

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4
Q

GnRH continuous inhibit

A

LH, FSH

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5
Q

what is Somatropin?

A

recombinant Human GH (rhGH)

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6
Q

what are the direct effects of somatropin

A

are the result of GH binding its receptor on target cells. For example, Adipocytes & lipolysis.

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7
Q

what are the indirect effects of somatropin

A

are mediated primarily by an IGF-I, a hormone that is secreted from the liver and other tissues in response to GH.

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8
Q

what are 4 clinical uses of recombinant Growth hormone

A
  1. Growth: Growth failure in paediatric patients associated with:
  2. Improved metabolic state, increased lean body mass, sense of wellbeing
  3. Increased lean body mass, weight, and physical endurance
  4. Improved gastrointestinal function
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9
Q

what are adverse effects of GH?

A
  • Pseudotumor cerebri, slipped capital femoral epiphysis, scoliosis, edema, hyperglycemia, asphyxiation in severely obese patients with Prader-Willi syndrome
  • Patients with turner syndrome—> risk of otitis media
  • Pancreatitis, gynecomastia, and nevus growth
  • Peripheral edema, myalgia, and arthralgia
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10
Q

what is contraindications for GH:

A

Malignancy

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11
Q

Mecasermin is recomnbinant __________

A

human IGF-1

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12
Q

what are the uses for Mecasermin?

A
  • Treatment of severe IGF-1 deficiency that is not responsive to GH
  • Laron syndrome (most common cause of growth hormone insensitivity and caused by mutations in the GH receptor gene)
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13
Q

Adverse effects of Mecasermin:

A

-Hypoglycemia
-Intracranial hypertension
-lipohypertrophy
- elevation of liver enzymes

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14
Q

approaches to growth hormone excess

A

transphenoidal ssurgery , radiation and drugs

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15
Q

medications to RX. growth hormone excess?

A

somatostatin analogs : Octreotide, Lanreotide

Growth hormone receptor antagonist: Pegvisomant

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16
Q

what is the mechanism of action for Octreotide & Lanreotide

A

Somatostatin analog–> Inhibiting:
GH, IGF-1
TSH, LH
Glucagon, insulin, pancreatic polypeptide
Serotonin
VIP
Secretin
Gastrin

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17
Q

list 2 drugs that are given to treat:
Acromegaly, gigantism
Carcinoid tumor, gastrinoma, glucagonoma
Insulinoma, VIPoma, ACTH secreting tumor
Secretory diarrhea, portal hypertension
Control of bleeding from esophageal varices

A

Octreotide & Lanreotide

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18
Q

what is the Adverse effect for Octreotide & Lanreotide

A

Nausea, vomiting, abdominal cramps, flatulence, steatorrhea, biliary sludge, gall stones, hypertension, peripheral edema, alopecia, bradycardia, vitamin B12 deficiency

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19
Q

list 5 uses for Octerotide & Lanreotide

A

Acromegaly, gigantism
Carcinoid tumor, gastrinoma, glucagonoma
Insulinoma, VIPoma, ACTH secreting tumor
Secretory diarrhea, portal hypertension
Control of bleeding from esophageal varices

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20
Q

MOA for Pegvisomant

A

binds to the GH receptor –>blocking the binding of endogenous GH —> prevents activation of JAK-STAT signaling or stimulation of IGF-1 secretion–> normalizes serum IGF-1

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21
Q

uses for Pegvisomant

A

Acromegaly
Alternative for use in patients not respond to SST

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22
Q

what is the adverse effects for Pegvisomant

A

Diarrhea, antibody formation, elevation of liver transaminase, Lipohypertrophy

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23
Q

RX. in short stature

A

replacement in GH deficiency
- somatotropin (recombinant of human GH)

replacement in Laronn syndrome
- mecasermin (recomb. of IGF-1 as GH receptor protein, High GH but no IGF-1 so cant grow )

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24
Q

RX. for acromegaly

A

inhibition of GH release
- OCTREOTIDE = somatostatin analog

inhibit of GH receptor activation
- pegvisomant= GH antagonist

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25
Q

state the hypothalamic - pituitary - Gonadal - axis PATHWAY

A

GnRH –>Gq-IP3-PLC-DAG-Ca–> LH & FSH –> Ovaries & Testis –>androgens, estrogens & progesterone
Preovulatory surge of estrogen–> ↑ GnRH

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26
Q

Signaling pathway for FSH, LH, hCG

A

cAMP

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27
Q

Menotropins is for development of

A

[human menopausal gonadotropin - hMG]
Both FSH & LH, follicle development in women

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28
Q

Follitropin alfa and beta is recombinant_____

A

FSH

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29
Q

what is the use of gonadotropins?

A

rx: of infertility in women/ men
- Menotropins ->Spermatogenesis
hCG [LH] –> Testosterone production

Cryptorchidism - hCG

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30
Q

what is the adverse effects of gonadotropins

A

Multiple pregnancies and the ovarian hyperstimulation syndrome [OHSS]

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31
Q

list 4 Gonadotropin Releasing Hormone Agonists

A

Gonadorelin, Leuprolide, Nafarelin & Histrelin

32
Q

MOA of GnRH agonists

A

GPCR – IP3 –> pulsatile administration –> ↑ FSH, LH –> continuous administration –> down regulation of GnRH receptors –>↓ FSH, LH –>↓ estrogen, testosterone

33
Q

uses of GnRH agonists

A

Advanced prostate cancer, breast cancer, endometriosis, and uterine fibroids, central precocious puberty, suppress premature LH surge in the treatment of infertility.

34
Q

Adverse effects of GnRH agonist

A

Hot flashes, depression, diminished libido, generalized pain, vaginal dryness, and breast atrophy

35
Q

list 3 GnRH antagonists:

A

Ganirelix, Cetrorelix & Degarelix

36
Q

MOA of GnRH antagonists:

A

Competitive antagonist at GnRH receptors–> ↓ IP3 –>↓ FSH & LH

37
Q

what are some uses of GnRH antagonists:

A

Infertility, inhibits premature LH surge in women ovarian hyperstimulation
Prostate cancer: ↓ Testosterone

38
Q

what are adverse effects and contraindication of GnRH antagonists:

A

Hypersensitivity, allergy and anaphylaxis

Contraindications:
Pregnancy

39
Q

MOA of Follitropin alpha

A

Activates FSH receptors

40
Q

indications of Follitropin alpha

A

Controlled ovarian stimulation, Infertility due to hypogonadotropic hypogonadism in men (MHH)

41
Q

adverse effects of Follitropin alpha

A

Multiple pregnancies, gynecomastia in men

42
Q

MOA of hCG

A

Agonist at LH receptors

43
Q

indications of hCG

A

Initiation of final oocyte maturation and ovulation during controlled ovarian stimulation, MHH

44
Q

Adverse effects of hCG

A

depresssion

45
Q

MOA of Leuprolide

A

GnRH agonist. Increase LH & FSH secretion with intermittent administration. Reduced LH and FSH secretion with continuous admn.

46
Q

indications of Leuprolide

A

Ovarian suppression, controlled ovarian stimulation, central precocious puberty, prostate cancer, endometriosis, breast cancer

47
Q

adverse of Leuprolide

A

Headache, nausea

48
Q

MOA of ganirelix

A

Blocks GnRH receptors, reduces endogenous LH, FSH

49
Q

indications of ganirelix

A

Prevention of premature LH surge during controlled ovarian stimulation

50
Q

adverse effects of ganirelix

A

headache, nausea

51
Q

MOA of prolactin

A

-Mammary gland –> tissue growth & milk production in the presence of estrogen & progestin
-Prolactin secreting adenoma & TRH–> Hyperprolactinemia —> infertility & galactorrhea —> inhibits GnRH –> inhibits ovulation in females & spermatogenesis in males –> hypogonadism –> osteoporosis
-Dopamine antagonists –> hyperprolactinemia

52
Q

list 2 drugs that activate dopamine D2 receptors

A

Cabergoline or bromocriptine:
(Dec. prolactin)

53
Q

uses of Cabergoline or bromocriptine:

A

Hyperprolactinemia, mixed growth hormone and prolactin secreting pituitary adenoma

54
Q

adverse effects of Cabergoline or bromocriptine:

A

Nausea, headache, dizziness, vasospasm, psychosis, etc.

55
Q

Drugs that block __________________ cause hyperprolactinemia by blocking the inhibitory effects of endogenous ______ on the pituitary cells that release prolactin

A

dopamine D2 receptors , dopamine

56
Q

The older antipsychotic drugs (______________________________ are most likely to be the pharmacologic cause of hyperprolactinemia.

A

e.g., phenothiazines, haloperidol), with their strong dopamine D2 receptor-blocking activity,

57
Q

Drugs or drug groups that cause hyperprolactinemia through mechanisms that are not well characterized include (4)

A

methyldopa (an antihypertensive), amphetamines, tricyclic and other types of antidepressants, and opioids.

58
Q

clinical uses for oxytocin

A

To induce & augment labor
Milk letdown reflex
To control of uterine hemorrhage after delivery

59
Q

adverse effects for oxytocin

A

Excessive stimulation of uterine contractions before delivery can cause fetal distress, placental abruption, uterine rupture, fluid retention, hyponatremia, heart failure, seizures, and death

60
Q

contraindications for Oxytocin

A

Fetal distress, prematurity, cephalopelvic disproportion

61
Q

MOA for Atosiban

A

Antagonist of oxytocin receptor used to suppress preterm labor

62
Q

Desmopressin MOA

A

Long acting, intravenously, subcutaneously, intranasally, or orally

63
Q

Vasopressin MOA (V1):

A

V1 of vascular smooth muscle –> Gq +PLC +IP3 –> vasoconstriction

64
Q

Vasopressin MOA (V2):

A

V2 of renal tubular cells –>Gs + AC–> ↑ water permeability & reabsorption; extra-renally release of factor VIII and von Willebrand

65
Q

Vasopressin uses:

A

Pituitary diabetes insipidus, nocturnal enuresis, esophageal variceal bleeding, hemophilia A and von Willebrand disease

66
Q

what are the adverse effects for vasopressin:

A

Headache, nausea, abdominal cramps, agitation, and allergic reactions

67
Q

MOA for Conivaptan

A

antagonist of V1a and V2 receptors

68
Q

uses for Conivaptan

A

Hypervolemic, euvolemic hyponatremia, SIADH, & heart failure

69
Q

uses for tolvaptan

A

Autosomal dominant polycystic kidney disease, SIADH, cirrhosis.

70
Q

MOA for tolvaptan

A

more selective for V2 –>↑ free water clearance –>↓ urine osmolality –> ↑ serum sodium concentrations.

71
Q

Demeclocycline & Lithium MOA

A

act on the collecting tubule cell to diminish its responsiveness to ADH, thereby increasing water excretion.

72
Q

uses for Demeclocycline & Lithium

A

SIADH

73
Q

Adverse effects of Bromocriptine, Cabergoline

A

GI, orthostatic hypotension, psychosis, vasospasm

74
Q

Adverse effects of OXYTOCIN

A

Fetal distress, uterine rupture

75
Q

Adverse effects of desmopressin

A

GI, hyponatremia

76
Q

adverse effects of conivaptan

A

Infusion reactions

CAS 3 (10 decks)

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