Pituitary drugs Flashcards
Which drug is a direct agonist of the GH receptor?
Somatotropin (rGH)
Which drug directly activates IGF-1 receptors?
What is this more detailed drug’s MoA?
Mecasermin (rIGF1)
Is a downstream effector of GH
Bypasses GHR defects and/or anti-GH ABs
Activates the IGF1R
Name two SS analogues.
Octreotide, lanreotide
Indications for Somatotropin (rGH)?
- HRT for children w/ GH deficiency
- Other conditions of small stature: Prader-willi syndrome; Turner’s syndrome; Noonan’s syndrome; Chronic renal insufficiency; Idiopathic short stature
Which drug is an antagonist of the GH receptor?
Pegvisomant
Indications for Mecasermin (rIGF1)?
Children with impaired growth
non-responsive to GH: e.g. mutations in GHR or downstream signaling pathway, neutralizing antibodies to GH, or IGF-1 gene defects (v. rare)
Indications for octreotide, lanreotide?
- GH excess: gigantism, acromegaly.
- Other clinical uses: Esophageal varices; Carcinoid syndrome; Gastrinoma; glucagonoma
- [sketchy: insulinoma, VIPoma, ZE syndrome]
Indications for pegvisomant?
GH excess; gigantism; acromegaly
Adverse effects of somatotropin (rGH)? (adults, children)
Children: - Idiopathic intracranial HTN - Increased intraocular pressure - Development of insulin resistance Adults: - Peripheral edema - Arthralgias - Carpal tunnel - Parathesis - Worsening glucose intolerance - Acute pancreatitis
Adverse effects of mecasermin (rIGF1)?
- Hypoglycemia (insulin-like)
- Intracranial HTN
- Increased liver enzymes
Adverse effects of octreotide, lanreotide?
Nausea/Diarrhea (~50%)
Gallstones (~25%)
Suppresses TSH (monitor for hypothyroidism low risk- typically only transient effect) Bradycardia & cardiac arrhthymias
Adverse effects of Pegvisomant?
None listed
Contraindications for somatotropin? (rGH)
- Active malignancy
- Uncontrolled diabetes
- Proliferative retinopathy
- Children with closed epiphyseal plates (won’t be effective)
- Prader-willi with severe obesity and/or respiratory obstruction
Contraindications for mecasermin?
- Active neoplasm
- Children with closed epiphyseal plates
What drugs are GnRH agonists?
Leuprolide Goserlin Buserlin Triptorelin Naferelin
Lewd-pro (Jeremy) ‘Lin’ activates the gonads.
How do GnRH agonists affect gonadotropin release?
Sustained activation of GnRH receptor inhibits release of gonadotropins (even though they’re agonists)
Indications for GnRH agonists?
- Controlled ovarian stimulation.
- Palliative therapy of hormone-dependent tumors.
- Suppression of inappropriate growth of hormone-dependent tissues (e.g. endometriosis and fibroids).
- Tx of precocious puberty.
- Suppression of endogenous puberty in gender dysmorphic adolescents.
What drugs are GnRH antagonists?
Ganirelix
Cetrorelix
Degarelix
‘Relax’ the gonads.
How do GnRH antagonists affect gonadotropin release?
Antagonize GnRH receptors, reduce gonadotropin release. (as expected)
What are the indications for ganirelix + cetrorelix?
What are the indications for degarelix?
Ganirelix + cetrorelix: controlled ovarian stimulation.
Degarelix: advanced prostate cancer
“D” = dick (prostate).
When are ALL GnRH agonists and antagonists contraindicated?
Pregnancy
What are the SE’s of ALL GnRH agonists and antagonists?
Side effects associated with gonadal hormone deprivation:
- Hot flashes
- Decreased bone density
- Vaginal dryness/atrophy
- ED
Although both GnRH agonists and antaognists ultimately inhibit release of gonadotropins, which provides an initial gonadotropin “flair”?
GnRH agonists
AKA Lewd-pro (Jeremy) ‘Lin’ activates the gonads.
What does hMG stand for?
Human menopausal gonadotropin
What is hMG made up of?
Menotropins: FSH/LH
What is urofollitropin and follitropin (alpha/beta)?
FSH and rFSH
What is FSH (urofollitropin, follitropin) and hMG used for?
Female: FSH and hMG used to stimulate follicular development.
What is hCG used for in females? Males?
- Females: hCG used to trigger ovulation via the LH receptor.
- Males: hCG used to trigger endogenous testosterone synthesis via the LH receptor.
What are hMG, urofollitropin, follitropin, and hCG indicated for in females? Males?
Females: Infertility treatment in anovulatory women. Ovarian hyperstimulation (in assisted reproductive surgery).
Male: infertility in hypogonadotopic hypogonadism.
Side effects for hMG, urofollitropin, follitropin, and hCG in females? Males?
Female: multiple pregnancies.
Ovarian hyperstimulation syndrome (increased vascular permeability/potentially life-threatening)
Male: gynecomastia
Oxytocin: MoA? (cellular)
Acts through cognate GPCR expressed on uterine smooth m. cells and breast.
Desmopressin: MoA?
Selectively activates V2 vasopressin receptors in kidney to promote water reabsorption (via ADH).
Activates V2 receptors on endothelial cells to release vWF.
Vasopressin: MoA?
Direct full agonist of both V1 and V2 vasopressin receptors (ADH).
Conivaptan: MoA?
Antagonizes both V1 & V2 receptors (for ADH).
Promotes increased water excretion and raises serum Na+.
(coni - 2 syllables)
Tolvaptan: MoA?
Selectively blocks V2 (ADH) receptors.
tol - 1 syllable
Oxytocin: indications?
- Induction of labor requiring expedited vaginal delivery (e.g. uncontrolled diabetes; worsening pre eclamsia; Intrauterine infection; Ruptured membrane protracted labor)
- To treat uterine atony (failure of uterus to contract following delivery)
Desmopressin: indications?
- Neurogenic Diabetes Insipidus
- Nocturnal enuresis
- Minor bleeding in mild hemophilia A & von Willebrand’s disease
Vasopressin: indications?
Second line agent used in tx of vasodilatory shock refractory to epinephrine
Conivaptan/tolvaptan: indications?
Hypervolemic hyponatremia due to SIADH
Oxytocin toxicity?
Toxicity is rare
Excessive stimulation of uterine contractions can cause fetal distress, placental abruption or uterine rupture
At very high concentrations can activate vasopressin receptors leading to excessive fluid retention
Desmopressin toxicity?
Headache, hyponatremia, acute thrombotic events (rare).
Vasopressin toxicity?
- Atrial fibrillation
- Low cardiac output
- Cardiac arrhthymia
- Hyponatremia
Conivaptan/tolvaptan toxicity?
Tolvaptan: associated w/ hepatotoxicity (tx limited to < 30d); also a/w osmotic demylination syndrome [central pontine demyelination]
