Flashcards in Intro to Endo Drugs Deck (17)
How is specificity achieved in endocrine signalling?
target tissue specificity: type and number of receptors in a tissue
hormone-receptor specificity: the ability of hormone to interact w its receptor, & not others
What are nuclear receptors?
ligand dependent transcription factors that work through common mechanism of action
How do hypothalamic releasing hormones get to the ant pituitary?
made by hypothalamic neurons, transported to median eminence, secreted into portal circulation
What are the six steps in which defects in endocrine systems can occur?
transport to site of action
interxn w receptor on target
initiation of biological response (stimulus-response coupling)
termination/antagonism of response
degradation/elimination of hormone
What are the different causes for a lack of hormone?
incomplete biosynthesis (CAH)
reduce signal for synthesis/secretion (or no receptor for it)
loss of gland that secretes hormone (type I DM, Hashimotos, Addisons)
iatrogenic suppression/loss of secreting gland
What are different things that can cause a hormone to be present but not work properly?
altered form of hormone
altered receptors --> HORMONE RESISTANCE (androgen insensitivity, laron's dwarfism)
post-receptor activity altered --> RESISTANCE (PTH resistance from mutations in G protein, insulin or GH resistance)
What can secondarily alter the function of a hormone?
trauma or stress (insulin resistance during stress)
impaired hormone metabolism (impaired vitamin D --> hyperparathyroidism)
drug interxns w other hormone systems (something that displaces from carrying protein)
What things can cause hormone excess?
loss of negative feedback
What are treatment options for a lack of hormone?
hormone replacement therapy
stimulate natural secretion - direct or indirect
What are treatment options for too much hormone?
inhibit biosynthesis or secretion
interfere w or oppose actions of hormones (functional antagonists)
remove gland, then hormone replacement
What are 5 determinants of hormone/drug action?
site of action (law of mass action)
hormone and drug metabolism (drug-drug interxns)
What is hormone spillover responsible for?
lots of side effects seen w drugs and hormones - may just be able to reduce the dose
What is an example of cross-coupling?
estrogen cause increase in receptors for oxytocin on uterine muscle during 3rd trimester
How are steroids and peptides degraded?
steroids - converted to less active through oxidation and conjugation
peptides - degraded by proteolysis (can't take orally)
What are the different ways to measure hormones?
chemical (HPLC, chromatography/mass spec) - catecholamines and urinary cortisol
immunological methods (RIA, ELISA)
radioreceptor (receptor binding) assay
What is the caveat of immunological methods to measure hormones?
doesn't always correlate w biological activity since Ab binding site usually not active site