Endocrine Pharmacology: Hypothalamus & Pituitary Flashcards
What stucture of the hypothalamus secretes ADH (vasopressin) and oxytocin?
Supraooptic and paraventricular nuclei
What are the hormones released by the anterior pituitary gland?
TSH, ACTH, FSH, LH, GH, PRL
What are the hormones released by the posterior pituitary gland?
Oxytocin & Vasopressin (ADH)
What is the receptor of GH & PRL?
JAK/STAT
What is the receptor of GHRH, TSH, FASH, LH, ACTH, & Vasopressin?
Gs
What is receptor of Dopamine, SST?
Gi-coupled GPCRs
What is the receptor of GnRH, Ocytocin & Vasopressin 1A&B?
Gq coupled GPCRs
How are we able to diagnose GH deficiency? Explain
Injecting exogenou GH into the body. If GH levels increase (Hypothalamic disorder), GH levels remain low (anterior pituitary problem)
How would you describe Peptide hormones?
unbound in the plasma, receptor is at the cell membrane (lipophobic), fast onset of effects
What are the different peptide hormones?
Pituitary hormones, hypothalamic releasinghormones, Insulin, Glucagon, Calcitonin, PTH
How would you describe steroid hormones?
Protein-bound in plasma, receptors are in the cytoplasm (lipophilic), slow onset of effects
How would you describe AA derivatives of hormones that function like steroids?
Protein-bound, receptor is at the nucleus (lipophilic), and slow onset of effects
What are examples of AA derived hormones that act like steroids?
T3, T4
How would you describe AA derived hormones that function like peptides?
Unbound in plasma, receptor is at the cell membrane (lipophobic), and fast onset of effects
What are the diff hormones derived from AA and function like peptides?
Dopamine, Epinephrine & NRE
What classification of drugs are used to tx giganistism & dwarfism?
GH & GH regulators
What are the 4 GH regulators?
Somatostatin, GH, Mecasermin, & Pegivosomant
What is a GH-inhibiting hormones from the hypothalamust that inhibits Gastrin release from G cels & histamine release from enterochromaffin cells?
Somatostatin
What cells secrete Somatostatin?
D cells of the pancrease & D cells of the GI tract
What is the effect of Somatostain releae?
Inhibition of GH, TSH, Insulin, Glucagon, Gastrin & Other GI hormone release
What are the 2 SST analogs and which of them has less side efefcts, longer DOA, more potent & has less rebound hypersecretion?
2 Analogs: Octreotide & Lanretoide
Which of them: Octreotide
What conditions are SST analogs used for?
Acromegaly, Giganitism, Hormone-secreting tumors & Bleeding esophageal varices
What is a significant AE of SST analogs?
Gallstone
What are the direct & indirect effects of GH?
DIrect effects: INC lipolysis & blood sugar + anti-insulin effects
Indirect effects: Skeletal growth, INC cell proliferation, INC protein anabolism
What is the only preparation of GH?
Somatropin
What are the therapeutic uses of Somatropin?
GH deficient children & adults (Prader-Willi syndromes, CKD in pedia px, SGA babies <2yo)
Non-GH deficient/Idiopathic short stature children
Wasting in AIDS px
What are the AE of Somatropin?
Children (rare): Intracranial HPN, Scoliosis & Hypothyroidism
adults: Peripheral edema, MYALAGIA, ARTHRALGIA
What GH agonist is used for children unresponsive to GH therapy and stimulates skeletal muscle growth, AA transpo, protein synthesis, & cell proliferation?
What is a significant AE of this drug?
Mecasermin
Hypoglycemia
What is a GH receptor antagonist blocks peripheral effects of GH causing DEC of IGF-1 used for patients w/ Acromegaly who are unresponsive to Somatostatin analogs?
What is a common AE in Pegvisomant?
Pegvisomant
CHange in liver function test
What is the main use of drugs that antagonize or mimic gonadostropins?
Infertility
What is the physiologic process of GnRH release from the hypothalamus?
Controls the release and synthesis of FSH & LH
What determines the effect of GnRH analogs? How so?
On how they are administered
If administered in pulsatile matter —> stimulates synthesis and release of Gonadotropin —> mimics physiologic release of GnRH
If administered continuously —> inhibits synthesis & release of Gonadotropin
What are the therapeutic uses of GnRH analogs?
Pituitary stimulation
Suppression of Gonadotropins
In what conditions do we use GnRH analogs?
Hypogonadotropic hypogonadism —> male/female infertility
Initiate ovulation in Assisted Reproductive Technology procedures —> triggers ovulation
In what conditions are GnRH analogs used for suppression of Gonadotropins?
Endometriosis
Central precocious puberty
Prostatic/Breast cancer & Uterine Leiomyoma
Assisted Reproductive Technology
Early pubertal transgender adolescents
How do GnRH analogs affect ART to suppress Gonadotropins?
Inhibition of endogenou LH surge to prevent premature ovulation —> DEC ART cycle cancellation rates —> INC pregnancy rates
What are the diff preparations of GnRH analogs?
-relin = “release”
LeuproRELIN - PH available
GosereRELIN - PH available
TriptoRELIN
NafaRELIN
What is the common AE of GnRH analogs?
Biphasic response
What is the MOA of GnRH antagonist?
Directly blocks GnRH receptors in the APG preventing effects of endogenou GnRH
What are the preparations of GnRH antagonists?
-relix = “antagonize”
CetroRELIX
GaniRELIX
DegaRELIX
For what are GnRH antagonists used for?
To suppress secretion of Gonadotropin
Female infertility, Adv prostate cancer, & Endometriosis
What drugs are used for advanced prostate cancer , Female infertility, & Endometriosis?
-x = “antagonize”
Elagolix - Endometriosis
Abarelix & Degarelix = Advanced prostate cancer
Ganirelix & Cetrorelix = Suppress LH surge that can prematurely trigger ovulation —> tx female infertility
What is the most common AE of GnRH antagonist?
Nausea & headache
Estrogen/Androgen-deprivation: Hot flash, sweats, depression, decreased libido
What are the functions of FSH?
Stimulates gamotegenesis
Stimulates steroid production —> Estradiol & Testosterone production
What are the functions of LH?
Regulation of gonadal steroid hormone production
What gonadotropic hormone stimulates ovarian corpus lutem to produce progesterone —> maintains placenta?
HCG
Where is hCG secreted from?
Synctiotrophobalts from the placenta
What are the diff preparations of FSH?
-pin
MentroPIN - postmenopausal women
UrofollitroPIN - taken from urine of postmeonopausal women
RFSH - purified recombinant form of FSH
What are the pure preparations of LH used as LH analogs?
HCG
RhCG
RLH/Lutropin
What are the different uses of Gonadotropin hormone analogs?
Female infertility
Male infertility
Cryptorchidism - undescended testes of a boy
What type of male infertility disorders cause the need for Gonadotropin hormone analogs?
HYPERgonadotropic/Primary Hypogonadism
HYPOgonadotrpoic/Secondary Hypogonadism
What are the AEs of Gonadotropin hormone analogs?
Multiple pregnancies
Ovarian Hyperstimulation
Headache & Depression
Gycenomastia
What happens during assisted reproductive technology? Explain the process.
- Start w/ FSH preparation —> stimualte folicular growth and steroidal genesis
- LH may be added especially in hypogonadotropic women for adequate estrogen production
- Follicles grow —> Estrogen production INC —> Premature ovulation —> GnRH agonist/antagonist given —> Harvest egg at proper time
If GnRH agonist —> start early before start of FSH tx bcos of initial rise in Gn secretion
If GnRH antagonist —> start on Day 7 —> immediate effects
- Follicular #s and size monitors through ultrasound —> ideal size obtained —> LH prep (hCG) given —> final oocyte maturation —> Progesterone given (improved uterine receptivity)
- Egg retrieval after 34-46hrs —> eggs are incubated w/ sperm —> embryo egg is inserted to uterine cavity
What are the diff dopamine agonists?
BromocriptINE (Parlodel) —> most improtant
Carbergoline
Quinagolide
What is the MOA of dopamine agonists?
Diba Dopamine inhibits PRL? Sooo….
It inhibts PRL release from the anterior pituitary gland
Acts on D2 receptors
What are the therapeutic uses for Dopamine agonists?
Hyperprolactinemia
Inhibit physiologic lactation
Parkinsons’ disease
Acromegaly
Diabetes
What are the preparations of Dopamine agonists and which drug is improtant for a specific condition?
Bromocription & Cabergoline
Bromocriptione - postpartum women who do not intend to breastfeed
What is the stimulus for Oxytocin & what are its effects?
Stimulus: Infant suckling & Cervical dilation
Effects:
- Uterine contraction
- Milk ejection (lactating women)
- Weak antidiuretic @ high concentrations
What are the therapeutic uses of Oxytocin?
Ocytocin challenge test/Contraction stress test
Induce labor
Augment uterine contractions
Prevent/Tx Postpartum hemorrhage
Not really used for impaired milk ejection
What is the preparation of Oxytocin?
Demoxytocin (IV/IM)
What are the AEs of Oxytocin administration?
Uterine rupture
Fetal death
Abruptio placentae —> premature separation of the placenta, compromising fetal blood supply
Hypotension in bolus doses
What are the C/Is of Oxytocin?
Fetal distress
Prematurity
Cephalopelic disproportion
Abnormal fetal presentation
Placental abruption worsens the condition
Predisposition to uterine rupture
What are the uses for Oxytocin antagonist?
Tocolysis in preterm labor
Relax uterine muscles —> delayed labor
What is the preparation of Oxytocin antagonist?
Atosiban (Tractocile)
In what condition can we secrete ADH/Vasopressin?
If INC plasma tonicity, LOW BP —> INC ADH —> antidiuresis, H2O retention —> INC BP
What are the 2 types of Vasopressin/ADH receptors?
V1 (Gq) - vascular smooth muscles —> vasoconstriction
V2 (Gs) - acts in renal tubule cells —> free H2O reabsoription in CTs
What are the types of preparation of Vasopressin? Which of those 2 is long-acting?
Desmopressin (oral) —> LONG ACTING
Vasopressin (Parenteral)
What are the therapeutic uses of Vasopressin?
Diabetes insipidus
Noctorunal enuresis
Hemophilia A, vWD
Bleeding esophageal varices
What are the common AE of vasopressin & its C/I?
GIT disturbance, headache, overdose,
C/I: px w/ CAD
What are the 2 Vasopressin antagonist?
ConiVAPTAN
TolVAPTAN
What is the therapeutic use of Conivaptan? AE? C/I?
Use: Hypervolemic/Euvolemic hyponatremia (hospitalized px)
AE: Orthostatic hypotension
C/I: Hypovolemic hyponatremia
Produces water diuresis
What are the uses, AEs, & C/Is of Tolvaptan?
Uses:
- HF when other diuretics don’t work
- Hypervolemic/Euvolemic hyponatrmia
- SIADH
AEs: Thirst, dry mouth, nausea, polyuria, Liver toxicity
C/I: Liver disease
