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CAS 3 > Drugs for hypothalamic and pituitary disorders > Flashcards

Drugs for hypothalamic and pituitary disorders Flashcards

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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
state the hypothalamic - pituitary - Gonadal - axis PATHWAY
GnRH -->Gq-IP3-PLC-DAG-Ca--> LH & FSH --> Ovaries & Testis -->androgens, estrogens & progesterone Preovulatory surge of estrogen--> ↑ GnRH
26
Signaling pathway for FSH, LH, hCG
cAMP
27
Menotropins is for development of
[human menopausal gonadotropin - hMG] Both FSH & LH, follicle development in women
28
Follitropin alfa and beta is recombinant_____
FSH
29
what is the use of gonadotropins?
rx: of infertility in women/ men - Menotropins ->Spermatogenesis hCG [LH] --> Testosterone production Cryptorchidism - hCG
30
what is the adverse effects of gonadotropins
Multiple pregnancies and the ovarian hyperstimulation syndrome [OHSS]
31
list 4 Gonadotropin Releasing Hormone Agonists
Gonadorelin, Leuprolide, Nafarelin & Histrelin
32
MOA of GnRH agonists
GPCR – IP3 --> pulsatile administration --> ↑ FSH, LH --> continuous administration --> down regulation of GnRH receptors -->↓ FSH, LH -->↓ estrogen, testosterone
33
uses of GnRH agonists
Advanced prostate cancer, breast cancer, endometriosis, and uterine fibroids, central precocious puberty, suppress premature LH surge in the treatment of infertility.
34
Adverse effects of GnRH agonist
Hot flashes, depression, diminished libido, generalized pain, vaginal dryness, and breast atrophy
35
list 3 GnRH antagonists:
Ganirelix, Cetrorelix & Degarelix
36
MOA of GnRH antagonists:
Competitive antagonist at GnRH receptors--> ↓ IP3 -->↓ FSH & LH
37
what are some uses of GnRH antagonists:
Infertility, inhibits premature LH surge in women ovarian hyperstimulation Prostate cancer: ↓ Testosterone
38
what are adverse effects and contraindication of GnRH antagonists:
Hypersensitivity, allergy and anaphylaxis Contraindications: Pregnancy
39
MOA of Follitropin alpha
Activates FSH receptors
40
indications of Follitropin alpha
Controlled ovarian stimulation, Infertility due to hypogonadotropic hypogonadism in men (MHH)
41
adverse effects of Follitropin alpha
Multiple pregnancies, gynecomastia in men
42
MOA of hCG
Agonist at LH receptors
43
indications of hCG
Initiation of final oocyte maturation and ovulation during controlled ovarian stimulation, MHH
44
Adverse effects of hCG
depresssion
45
MOA of Leuprolide
GnRH agonist. Increase LH & FSH secretion with intermittent administration. Reduced LH and FSH secretion with continuous admn.
46
indications of Leuprolide
Ovarian suppression, controlled ovarian stimulation, central precocious puberty, prostate cancer, endometriosis, breast cancer
47
adverse of Leuprolide
Headache, nausea
48
MOA of ganirelix
Blocks GnRH receptors, reduces endogenous LH, FSH
49
indications of ganirelix
Prevention of premature LH surge during controlled ovarian stimulation
50
adverse effects of ganirelix
headache, nausea
51
MOA of prolactin
-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
list 2 drugs that activate dopamine D2 receptors
Cabergoline or bromocriptine: (Dec. prolactin)
53
uses of Cabergoline or bromocriptine:
Hyperprolactinemia, mixed growth hormone and prolactin secreting pituitary adenoma
54
adverse effects of Cabergoline or bromocriptine:
Nausea, headache, dizziness, vasospasm, psychosis, etc.
55
Drugs that block __________________ cause hyperprolactinemia by blocking the inhibitory effects of endogenous ______ on the pituitary cells that release prolactin
dopamine D2 receptors , dopamine
56
The older antipsychotic drugs (______________________________ are most likely to be the pharmacologic cause of hyperprolactinemia.
e.g., phenothiazines, haloperidol), with their strong dopamine D2 receptor-blocking activity,
57
Drugs or drug groups that cause hyperprolactinemia through mechanisms that are not well characterized include (4)
methyldopa (an antihypertensive), amphetamines, tricyclic and other types of antidepressants, and opioids.
58
clinical uses for oxytocin
To induce & augment labor Milk letdown reflex To control of uterine hemorrhage after delivery
59
adverse effects for oxytocin
Excessive stimulation of uterine contractions before delivery can cause fetal distress, placental abruption, uterine rupture, fluid retention, hyponatremia, heart failure, seizures, and death
60
contraindications for Oxytocin
Fetal distress, prematurity, cephalopelvic disproportion
61
MOA for Atosiban
Antagonist of oxytocin receptor used to suppress preterm labor
62
Desmopressin MOA
Long acting, intravenously, subcutaneously, intranasally, or orally
63
Vasopressin MOA (V1):
V1 of vascular smooth muscle --> Gq +PLC +IP3 --> vasoconstriction
64
Vasopressin MOA (V2):
V2 of renal tubular cells -->Gs + AC--> ↑ water permeability & reabsorption; extra-renally release of factor VIII and von Willebrand
65
Vasopressin uses:
Pituitary diabetes insipidus, nocturnal enuresis, esophageal variceal bleeding, hemophilia A and von Willebrand disease
66
what are the adverse effects for vasopressin:
Headache, nausea, abdominal cramps, agitation, and allergic reactions
67
MOA for Conivaptan
antagonist of V1a and V2 receptors
68
uses for Conivaptan
Hypervolemic, euvolemic hyponatremia, SIADH, & heart failure
69
uses for tolvaptan
Autosomal dominant polycystic kidney disease, SIADH, cirrhosis.
70
MOA for tolvaptan
more selective for V2 -->↑ free water clearance -->↓ urine osmolality --> ↑ serum sodium concentrations.
71
Demeclocycline & Lithium MOA
act on the collecting tubule cell to diminish its responsiveness to ADH, thereby increasing water excretion.
72
uses for Demeclocycline & Lithium
SIADH
73
Adverse effects of Bromocriptine, Cabergoline
GI, orthostatic hypotension, psychosis, vasospasm
74
Adverse effects of OXYTOCIN
Fetal distress, uterine rupture
75
Adverse effects of desmopressin
GI, hyponatremia
76
adverse effects of conivaptan
Infusion reactions

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