Endocrine Pharmacology Flashcards
Endocrine and exocrine example
Pancreas is exocrine (secretes digestive enzymes into GI tract), and an endocrine (secretes insulin, glucagon into blood)
steroird examples
cortisol aldosterone testosterone estrogen progesterone
peptide examples
insulin glucagon parathyroid hormone GH LH OT
tyrosine derivatives
EP
NE
DA
Thyroid
steroid hormones, bindding and breakdown
hydrophobic.
bound to carrier proteins
can permeate cell membrane
slow response: bind intracellular receptors, cause change in transcription (min-hours)
breakdown is slow: (Large fraction is bound to carrier, so there is large reserve of steroid in system, therefore breakdown is slow because only unbound are metabolized)
Peptide hormones, binding, breakdown
hydrophillic
not bound to carrier proteins. circulating [] reflects “active” []
cannot permeate PM
response very fast-bind cell surface receptors
breakdown fast- specific enzymes cleave
steroid hormone receptor
intracellular
have hormone binding domain and DNA binding domain
hormone-receptor complex interacts with DNA to influence transcription
ex: glucocorticoid receptor, estrogen receptor, thyroid hormone
GPCR
peptide hormone.
conformational change causes dissociation of G protein, signalling cascade.
ex: OT receptor, TSH, FSH
Receptor TK
peptide
conformational change causes dimerization, autophosphorylization, followed by recruitment downstream signalling molecules
ex: insulin receptor, GH
HPA axis-cortisol release
CRH from HTh controls ACTH release from anterior pituitary which controls release of cortisol from adrenal cortex
CRH is principle regulator
Insulin release control by circulating glucose
elevation of BG activates beta cells to secrete insulin. insulin reduces glucose (uptake/storage in liver, muscle etc), which reduces the stimulus for further insulin release
feedback
hormone released following stimulus
hormone response exerts feedback regulation on upstream control mechanism
control of lactation
suckling triggers OT release from posterior pituitary, leading to milk ejection and prolactin release from anterior pituitary leading to milk production. milk is released, baby continues feeding
POSITIVE FEEDBACK
Classifications of hypercortilism
tertiary: over secretion CRH from HTh
secondary: over secretion ACTH from anterior pituitary
primary: defect in primary hormone gland (adrenal)
treatment for hypersecretion
often tumor/intrinsic defect
theoretically-drug that blocks hormone receptor or synthesis of hormone.Not effective bc the drugs are expensive, not specific, too many SE
common- remove/ablate endocrine gland with surgery/radiation
treat hyperthyroidism
drugs that inhibit synthesis of thyroid hormones (thioamides) or radiation (radioactive iodine) to destroy cells in thyroid gland
treat: hyperaldosteronism
removal adrenal gland, drugs that block mineralcorticoid receptor (adlosterone antagonists) sometimes
treating hyposecretion of hormone
hormone replacement
hypoinsulinism (diabetes)
Insulin replacement throughout day to mimic natural release
Rapid/short acting insulin reaches peak formation quickly, used before meals
Intermediate/long acting ones used to control blood glucose over night or in btw meals
Growth hormone deficiency (pituitary dwarfism)
defects in pituitary gland = inadequate secretion of GH, slower bone growth and muscle development. replaced with injection SQ once day
Hypocortilism or chronic adrenal insufficiency (Addison’s disease)
symptoms: weight loss, hypoglycemia, hypotension, change in pigment, GI distrurbamce, change in hair distribution, can lead to adrenal crisis
defects in adrenal gland lead to insufficient production of corticosteroids including cortisol. can be treated by administering exogenous glucocorticoids (hydrocortisone, prednisone) to bring circulating levels closer to normal
ovarian cycle
- Follicular phase: E released by developing follicle, exerts neg FB on GnRH and FSH
- Ovulation: E levels cross threshold, begin to exert + FB on LH secretion, promoting LH surge and ovulation.
- Luteal Phase: follicle develops into corpus luteum, secreting high levels of E and P which exert - FB on GNRH,FSH,LH
- Menses: breakdown corpus lutuem, due to dimishing levels FSH/LH, causes shedding uterus lining
birth control pill
most combined=combined oral contraceptive (E+P)
exert - FB on GnRH, FSH, LH secretion
= no follicular development
= LG surge inhibited, no ovulation
tricks pituitary into thinking ovulation has occured. stops the release of FSH and LH, prevents development of follicle and ovulation. prevents normal release of hormones (e and P) from follicle and corpus luteum bc they dont develop
P only pill
thickens cervical lining
inhibit LH surge
Glucocorticoids
and SE from stopping
modulate HPA axis. often used to treat non-adrenal disorders bc anti-inflammatory and immunosuppresive action
SE: acute adrenal insuficiency “Farquharson Phenomen”- introduction of continuous exogenous hormone leads to atrophy in producing organ bc it suppresses natural production of that hormone.
so if stop, there is temporary atrophy of adrenal gland. develop addison disease symptoms
need to taper
