Week 4: Pharmodynamics- Nordgren Flashcards
toxicology
deals with adverse side effects on living systems (science of poisons)
Definition of pharmocology
study of substances (drugs) that interact with living species through chemical properties
drug receptor
cellular macromolecule that interacts with a drug ==> initiates a series of biochemical events
functions of a receptor
1) recognition of drug (ligand)- the receptor binds to drug/ligand
2) signal transduction- transfer of info
agonist
drug that activates molecular, biochemical, and physiological events associated with that interaction
pharmacologic dogma
a drug may increase or decrease cell function, but does not initiate new cell function
do drugs bind covalently with the receptor
no- if have such a strong interaction they will never let go
most receptors are…
proteins (enzymes)
transduction mechanisms can… (3 things)
alters receptor function (conformational change)
generate 2nd messenger (can lead to signal cascade)
impacts gene transcription
4 transduction mechanisms
1) G protein coupled receptor signal
2) ligand-gated ion channel
3) receptors as enzymes
4) receptors regulating nuclear transcription
most common type of transduction mechanism
g proteins
G protein coupled receptors (GPCRs)
most common drug receptor group
regulate 2nd messengers
ligand-gated ion channels
open up channel and allow ions to flow through
ligand binds ==> channel opens ==> ions flow through and down electrochemical gradient (can lead to depolarization of the membrane)
receptors as enzymes
when receptors bind they dimerize and form the perfect physical site for binding
can be inactivated or activated by ligand binding (kinases and phosphatases)
receptors regulating nuclear transcription
receptors have the ability directly bind to DNA regulate expression of adjacent genes
when receptor binds to ligand ==> chaperone will be inactivated
attributes of receptor-mediated processes
1) highly compartmentalized (receptor location and specificity)
2) self limiting on short time scale (bind then dissociate)
3) organized into opposing systems
4) provide opps for signal aplification
5) operate through a relatively small number of 2nd messengers (1 2nd messenger can signal different things depending on what is bound to the receptor)
many drug-drug interactions can be explained by this distinctive attribute or receptor-mediated biological processes:
a large number of different receptors may operate through a much smaller number of 2nd messenger systems
3 ways drugs can work by not interacting with receptors:
1) drugs interacting chemically with small molecules
2) drugs producing physiochemical effects
3) drugs that target rapidly dividing cells
cell-cell specific drugs functions
toxic to cells that are diving
include structural analogs that act by interfering with DNA/RNA
bind to DNA and cause strand breaks
occupancy theory
tissues responding to drugs often exhibit a saturable response- at some point you can keep adding drugs and nothing will happen
function of dose response curves
help us find 1/2 maximal effect
help us find what does we need to get max response
EC50
the [ ] of drug producing 50% of the maximal response and is an estimate of drug’s Kd
can also be written as ED50- the dose of drug producing 50% of the maximal response
affinity
describes the ability of a drug to form a complex with a receptor
characterized as 1/Kd
greater the affinity the lower the drug [ ] req’d to produce an effect
potency
relative position of dose-response curve
efficacy or intrinsic activity
the ability of a drug-receptor complex to produce a response
full agonist
drug capable of inducing a maximum response
partial agonist
drug that produces less than maximal response
antangonist
drug which inhibits the action of an agonist
pure antagonist
drug that binds to receptor that induces no response and has zero efficacy
competitive curve
competes for binding
dose response shifts to right
can still get same response- just need more drug
slope does not change
non-competitive antagonist
irreversible
maximal response reduced
slope reduced
apparent affinity changes little, if at all
compound A has a higher potency than compound B. What does this say about their response curves in relation to one another
the dose-response curve for A is well to the left of the that for B
compound A is said to be a non-competitive antagonist of compound B. What is true about this?
adding A reduces the response of the system to a fixed does of B and the addition of more B will not bring back the full response
physiological antagonism
involves interactions b/t regulatory pathways mediated by different receptors
ex: to affect your BP you can do stuff to your glucose levels
partial agonist
cant be explained by occupancy theory
may act like an antagonist when in the presence of a full agonist
inverse agonist
cant be explained by occupancy theory
without an antagonist present, it acts like an agonist but with an antagonist present it levels everything out (guessing i have no idea)
two state model
believes that the receptor exists in an active and inactive form
equilibrium exists b/t the 2
agonist ==> binds to active form ==> shift equilibrium to active form
inverse agonist ==> binds to inactive form ==> shift equilibrium to inactive form
partial agonist- small preference for active form
antagonist- does not preferentially bind to either form and does not alter the equilibrium b/t the active and inactive form of the receptor
spare receptors
occupancy of small % of receptors elicits a maximal response ==> system behaves like it has “spare” receptors (more than it needs)
quantal dose effect
all or none response
population response
cant be used to determine Kd or max efficacy
median effective dose (ED50)
dose producing effect on 50% of pop
hyperrecative
<ED50
dont need a lot of the drug to react
hyporeactive
> ED50
need a lot of the drug to react
tolerance
a form of hyporeactivity induced by repeated administration
tachyphylaxis
form of hyporeactivity induced rapidly after only a few doses
therapeutic index and what its numbers mean
measure of relative safety
high the number, safer it is
LD50- how much drug it takes to kill 50%
ED50- how much drug it takes to effect 50%
