Drugs for hypothalamic and pituitary disorders Flashcards
what are the cell cycle receptors for GH and PRL?
JAK/STAT
which hormones have GPCR receptors?
all except GH and PRL
GnRH in pulses –>promote
LH, FSH,
GnRH continuous inhibit
LH, FSH
what is Somatropin?
recombinant Human GH (rhGH)
what are the direct effects of somatropin
are the result of GH binding its receptor on target cells. For example, Adipocytes & lipolysis.
what are the indirect effects of somatropin
are mediated primarily by an IGF-I, a hormone that is secreted from the liver and other tissues in response to GH.
what are 4 clinical uses of recombinant Growth hormone
- Growth: Growth failure in paediatric patients associated with:
- Improved metabolic state, increased lean body mass, sense of wellbeing
- Increased lean body mass, weight, and physical endurance
- Improved gastrointestinal function
what are adverse effects of GH?
- 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
what is contraindications for GH:
Malignancy
Mecasermin is recomnbinant __________
human IGF-1
what are the uses for Mecasermin?
- 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)
Adverse effects of Mecasermin:
-Hypoglycemia
-Intracranial hypertension
-lipohypertrophy
- elevation of liver enzymes
approaches to growth hormone excess
transphenoidal ssurgery , radiation and drugs
medications to RX. growth hormone excess?
somatostatin analogs : Octreotide, Lanreotide
Growth hormone receptor antagonist: Pegvisomant
what is the mechanism of action for Octreotide & Lanreotide
Somatostatin analog–> Inhibiting:
GH, IGF-1
TSH, LH
Glucagon, insulin, pancreatic polypeptide
Serotonin
VIP
Secretin
Gastrin
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
Octreotide & Lanreotide
what is the Adverse effect for Octreotide & Lanreotide
Nausea, vomiting, abdominal cramps, flatulence, steatorrhea, biliary sludge, gall stones, hypertension, peripheral edema, alopecia, bradycardia, vitamin B12 deficiency
list 5 uses for Octerotide & Lanreotide
Acromegaly, gigantism
Carcinoid tumor, gastrinoma, glucagonoma
Insulinoma, VIPoma, ACTH secreting tumor
Secretory diarrhea, portal hypertension
Control of bleeding from esophageal varices
MOA for Pegvisomant
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
uses for Pegvisomant
Acromegaly
Alternative for use in patients not respond to SST
what is the adverse effects for Pegvisomant
Diarrhea, antibody formation, elevation of liver transaminase, Lipohypertrophy
RX. in short stature
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 )
RX. for acromegaly
inhibition of GH release
- OCTREOTIDE = somatostatin analog
inhibit of GH receptor activation
- pegvisomant= GH antagonist
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
Signaling pathway for FSH, LH, hCG
cAMP
Menotropins is for development of
[human menopausal gonadotropin - hMG]
Both FSH & LH, follicle development in women
Follitropin alfa and beta is recombinant_____
FSH
what is the use of gonadotropins?
rx: of infertility in women/ men
- Menotropins ->Spermatogenesis
hCG [LH] –> Testosterone production
Cryptorchidism - hCG
what is the adverse effects of gonadotropins
Multiple pregnancies and the ovarian hyperstimulation syndrome [OHSS]
list 4 Gonadotropin Releasing Hormone Agonists
Gonadorelin, Leuprolide, Nafarelin & Histrelin
MOA of GnRH agonists
GPCR – IP3 –> pulsatile administration –> ↑ FSH, LH –> continuous administration –> down regulation of GnRH receptors –>↓ FSH, LH –>↓ estrogen, testosterone
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.
Adverse effects of GnRH agonist
Hot flashes, depression, diminished libido, generalized pain, vaginal dryness, and breast atrophy
list 3 GnRH antagonists:
Ganirelix, Cetrorelix & Degarelix
MOA of GnRH antagonists:
Competitive antagonist at GnRH receptors–> ↓ IP3 –>↓ FSH & LH
what are some uses of GnRH antagonists:
Infertility, inhibits premature LH surge in women ovarian hyperstimulation
Prostate cancer: ↓ Testosterone
what are adverse effects and contraindication of GnRH antagonists:
Hypersensitivity, allergy and anaphylaxis
Contraindications:
Pregnancy
MOA of Follitropin alpha
Activates FSH receptors
indications of Follitropin alpha
Controlled ovarian stimulation, Infertility due to hypogonadotropic hypogonadism in men (MHH)
adverse effects of Follitropin alpha
Multiple pregnancies, gynecomastia in men
MOA of hCG
Agonist at LH receptors
indications of hCG
Initiation of final oocyte maturation and ovulation during controlled ovarian stimulation, MHH
Adverse effects of hCG
depresssion
MOA of Leuprolide
GnRH agonist. Increase LH & FSH secretion with intermittent administration. Reduced LH and FSH secretion with continuous admn.
indications of Leuprolide
Ovarian suppression, controlled ovarian stimulation, central precocious puberty, prostate cancer, endometriosis, breast cancer
adverse of Leuprolide
Headache, nausea
MOA of ganirelix
Blocks GnRH receptors, reduces endogenous LH, FSH
indications of ganirelix
Prevention of premature LH surge during controlled ovarian stimulation
adverse effects of ganirelix
headache, nausea
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
list 2 drugs that activate dopamine D2 receptors
Cabergoline or bromocriptine:
(Dec. prolactin)
uses of Cabergoline or bromocriptine:
Hyperprolactinemia, mixed growth hormone and prolactin secreting pituitary adenoma
adverse effects of Cabergoline or bromocriptine:
Nausea, headache, dizziness, vasospasm, psychosis, etc.
Drugs that block __________________ cause hyperprolactinemia by blocking the inhibitory effects of endogenous ______ on the pituitary cells that release prolactin
dopamine D2 receptors , dopamine
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,
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.
clinical uses for oxytocin
To induce & augment labor
Milk letdown reflex
To control of uterine hemorrhage after delivery
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
contraindications for Oxytocin
Fetal distress, prematurity, cephalopelvic disproportion
MOA for Atosiban
Antagonist of oxytocin receptor used to suppress preterm labor
Desmopressin MOA
Long acting, intravenously, subcutaneously, intranasally, or orally
Vasopressin MOA (V1):
V1 of vascular smooth muscle –> Gq +PLC +IP3 –> vasoconstriction
Vasopressin MOA (V2):
V2 of renal tubular cells –>Gs + AC–> ↑ water permeability & reabsorption; extra-renally release of factor VIII and von Willebrand
Vasopressin uses:
Pituitary diabetes insipidus, nocturnal enuresis, esophageal variceal bleeding, hemophilia A and von Willebrand disease
what are the adverse effects for vasopressin:
Headache, nausea, abdominal cramps, agitation, and allergic reactions
MOA for Conivaptan
antagonist of V1a and V2 receptors
uses for Conivaptan
Hypervolemic, euvolemic hyponatremia, SIADH, & heart failure
uses for tolvaptan
Autosomal dominant polycystic kidney disease, SIADH, cirrhosis.
MOA for tolvaptan
more selective for V2 –>↑ free water clearance –>↓ urine osmolality –> ↑ serum sodium concentrations.
Demeclocycline & Lithium MOA
act on the collecting tubule cell to diminish its responsiveness to ADH, thereby increasing water excretion.
uses for Demeclocycline & Lithium
SIADH
Adverse effects of Bromocriptine, Cabergoline
GI, orthostatic hypotension, psychosis, vasospasm
Adverse effects of OXYTOCIN
Fetal distress, uterine rupture
Adverse effects of desmopressin
GI, hyponatremia
adverse effects of conivaptan
Infusion reactions
