DRug receptors Flashcards
what is pharmacodynamic
what the drug does to the body
what is pharmacokinetics
what the body does to the drug
what is a ligand
substance that forms complex with receptors ex.drugs
what is a receptor
proteins that can bind to ligands
where can receptors be located
cell membrane
cytoplasm
nucleus
what does the receptor binding to the ligand do to post receptor signalling
activates or inactivates
what are the four receptor families
g protein coupled receptors
ion channels
enzyme linked receptors
intracellular receptors
what is the most common site of drug action
g protein coupled receptors
describe the structure of a receptor
single alpha helical peptide with seven transmembrane domains
extracellular domain contains the ligand binding area
describe the structure of a g protein
alpha subunit with diff forms
beta gamma subunit
what does the alpha subunit do
can bind to GDT and GTP
what does the BY subunit do
inhibits alpha subunit
how does the g protein function
occupied receptor changes shape and interacts with g protein which releases GDP and binds GTP. alpha subunit dissociates and activates adenylyl cyclase. hormone no longer present receptorconverts to resting state and GTP hydrolyzed to GDP
alpha subunits act on what? which on is inhibitory
adenylate cyclase
i is inhibitory
subunit q activates what
Phospholipase C
what are the second messengers activated by g proteins
camp
IP3
DAG
Ca
how do ligand channels work
ligand binding triggers confomational change in receptor and the channel opens
what is the ligand gated sodium channel
nicotinic acetylcholine
what is theligand gated calcium channel
NMDA
what is the ligand gated chloride channel
GABA
how are voltage gated channels different from ion gated
activated by changes in membrane ds potential not ligan
what is an ion pump
transmembrane protein that moves ions across pm against their concentration gradient
what is the cell membrane enzyme linked receptor
tyrosin kinase receptor
what is the structure of a tyrosin kinase receptor
spans the membrane in the form of dimers or multisubunit complexes
how does the tyrosin kinase receptor function
ligand binds to receptor causing a conformational change forming dimers and converts kinases to active forms
induces receptor autophosphorylation
what is an example of a intracellular enzyme lonked receptor
soluble guanylyl cyclase
what is the structure of guanylyl cyclase
forms hterodimer with alpha and beta subunit
regulatory domain
coiled coil domain
cyclase domain
how does guanylyl cyclase function
activated by nitroc oxide
activates second messenger cGMP
what is the structure of a intracellular nuclear receptor
ligand binding part and DNA binding part
in nucleus
how do nuclear receptors function
ligand diffuses into cell and interacts with the nuclear receptor then translocates to the nucleus
activated receptor binds to promoter region of gene resulting in gene expression
what is bmax
maximal specific bindign of a ligand to receptor
what is kd
concentration of drug where half maximal binding is observed
describe affinity
how attracted the drug is to the receptor
how does kd relate to affinity
as kd decreases the affinity increases
describe selectivity
preference for one receptor over another
what is e max
max effect induced by the drug
ec50
concentration of the drug that produces an effect that is half the max
describe potency
amount of drug needed to produce a given magnitude
describe efficacy
ability of a drug to elicit a biological response by agonist, determined by emax
what is an agonist
agent that can bind to a receptor and elicit a biologic response
what is a full agonist
produces max response, mimics
what is a partial agonist
activates receptor with a lower efficacy, will reduce effects of full agonist
what is an inverse agonist
has a negative effect on the receptor
what is an antagonist
drug combines wiht receptor but produces no response
how do competitive antagonists work
compete with agonist by binding to the same site on the receptor, can be overcome by increasing concentration of agonist
how do non competitve antagonists work
bond covalently or with such high affinity those receptors are unavailable to agonists
how do allosteric antagonists work
bind to allosteric site which prevents receptor from activating even when agonist is attached
define adverse effect
undesired harmful effect resukting from a medication
what is TD50
drug dose that produces toxic effect in 50% of patients
what is ED50
drug dose that produces therapeutic effect in 50% of patients
how is ED50 and EC50 different
EC is to reach 50% of max biological response which ED is for 50% to reach therapeutic response
how do you calculate the therapeutic index
TD50/ED50
what does it mean if TI is high
there is a wide therapeutic window so it has high safetyy
define idiosyncratic
individuals exhibit an unusual drug response
define tachyphylaxis
acute rapid loss of response to a drug
define tolerance
decreased response to a drug when the drug is taken repeatedly
what is receptor desensitization
mechanism that reduces the receptor response to an agonist
what are the four phases in drug development
1: small number, screen for safety
2: study efficacy
3: larger, safety and efficacy
4: large number post marketing studies
