Drugs Affecting Hypothalamic, Pituitary and Thyroid Function Flashcards
Anterior Pituitary Hormones
Hormones of the adenohypophysis or anterior pituitary or are essential for:
- Regulating growth and development
- Stimulating the reproductive system
- Providing a response to stress and
- Regulating intermediary metabolism
Anterior Pituitary Hormones
Synthesis and secretion of these hormones are controlled by:
- hypothalamic factors
- peripheral hormones
- drugs
Three Classes Anterior Pituitary Hormones
- Somatotropic hormones
- Glycoprotein hormones
- Proopiomelanocortin (POMC)
Somatotropic hormones
growth hormone (GH) and prolactin (Prl)
Glycoprotein hormones
thyrotropin (TSH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) (α-subunit the same, β-subunit different) Also, placental chorionic gonadotropin (CG)
Proopiomelanocortin (POMC)
derived hormones – corticotropin (ACTH), α- and β- melanocytestimulating hormones (α-MSH and β-MSH)
(GHRH)
Growth Hormone-Releasing Hormone
(GnRH)
Gonadotropin-Releasing Hormone
(TRH)
Thyrotropin-Releasing Hormone
(CRH)
Corticotropin-Releasing Hormone
Somatostatin negatively regulates secretion of?
GH and TSH
Dopamine inhibits secretion of?
Prl
GH has direct effects, but also acts on some target
tissues to produce?
Insulin-like growth factor 1 (IGF-1).
GH what occurs with Hypoglycemia & Hyperglycemia?
Hypoglycemia stimulates GH release, hyperglycemia
inhibits GH release.
GH effects?
Decrease Insulin sensitivity Increase Lipolysis Increase IGF-1 Increase Protein Synthesis Increase Epiphyseal (Bone) Growth
Somatropin is the generic name of all?
GH that is identical with hGH.
Somatrem is the generic name for?
GH with an additional methionine.
IGF-1 Deficiency?
IGF-1 deficiency occurs in a small number of children. They do not respond to hGH.
Mecasermin is a complex of?
hIGF-1 and hIGFBP-3 (IGF binding protein 3. The binding protein is necessary to produce a longer half-life.
Children with severe IGF-1 deficiency
usually have?
IGFBP deficiency also.
Growth Hormone Excess Causes?
(Gigantism and Acromegaly)
Somatostatin analogs are the best treatment when?
Pituitary surgery is impossible.
Most widely used drug for growth hormone excess and what are side effects?
Octreotide. 3x daily injections (short half-life)
Side effects are GI – diarrhea, nausea, abdominal pain.
A long-acting, slow release form Sandostatin-LAR
is available and is Injected once every
4 weeks.
Lanreotide is
Drug for growth hormone excess now available in the U.S.
Pegvisomant is?
Growth hormone receptor antagonist - treatment of acromegaly - decreases IGF-1.
PEG (polyethylene glycol) is?
Covalently bound - decreases renal clearance and so increases half-life.
Prolactin rises during?
Pregnancy, remains elevated until birth, and falls thereafter unless the mother breast-feeds her infant.
Hyperprolactinemia is?
Relatively common. Caused by pituitary adenomas (or diseases that interfere with dopamine signalling.)
Drugs used in treatment of hyperprolactinemia:
Cabergoline: Higher affinity for D2 receptors, longer half-life.
Bromocriptine: Not well tolerated, but FDA approved.
The gonadotropic hormones are?
LH, FSH and CG because of their actions on the gonads.
GnRH regulates systhesis and secretion of?
LH and FSH.
In men, LH acts on the testicular Leydig
cells to stimulate synthesis of?
Androgens, primarily testosterone, necessary for spermatogenesis.
Synthetic GnRH are available, but half lives are?
2 to 4 min.
What is Leuprolide and how is it special?
Synthetic GnRH. Analogues have substitutions at aa position 6 that inhibit proteolysis prolong half life plus C-terminal substitutions improve receptor binding
One synthetic GnRH (gonadorelin hydrochloride) is used for?
Diagnostic purposes to differentiate between pituitary and hypothalamic defects in patients with hypogonadotropic hypogonadism.
Chorionic gonadotropins (CG) is secreted by the placenta in early stages?
Of pregnancy.
Chorionic gonadotropins drug and action?
Pregnyl from urine of pregnant women, mimic action of LH and are used to treat infertility in women.
Urine from postmenopausal women contains?
FSH and LH, is called menotropin. Administered IM.
Recombinant FSH (rFSH) is also available? How is it admisitered?
(follitropin α and follitropin β). Administeded SC. These preparations are also used in women in treatment of infertility.
GnRH Receptor Antagonists drugs?
Cetrorelix and ganirelix and Degarelix.
Cetrorelix and ganirelix are?
Decapeptide antagonists of GnRH receptors used in in vitro fertilization. They delay premature LH surge.
Delays ovulation to allow collection of ova (controlled
ovarian hyperstimulation). Follows FSH therapy.
Degarelix is approved for?
Men with advanced prostate cancer. GnRH Receptor Antagonists.
GnRH Agonists drugs?
Leuprolide
Leuprolide is an agonist of and used in the treatment?
GnRH used in treatment of prostate cancer. Initially increases LH production, then decreases LH and testosterone dramatically due to receptor downregulation.
Thyrotropin-Releasing Hormone (TRH) drugs?
Thyrotropin alpha hTRH
Thyrotropin alpha hTRH Used in?
Diagnostics for thyroglobulin levels.
Corticotropin-Releasing Hormone (CRH) used for?
Used only for diagnostics. To distinguish Cushing’s disease from ectopic ACTH syndrome (tumors of lung, thymus, pancreas, thyroid, and adrenal gland).
