Pharmacodynamics Flashcards
Pharmacology
study of how function of living systems is affected by chemical agents study of physical and chemical properties and absorption and elimination of chemical agensts
pharmacokinetics
dose -> blood concentration -> receptor site concentration
- this is getting drug to site action and what body does to drug distribution and elimination
pharmacodynamics
receptor site concentration -> pharmacological réponse -> clinicat response therapeutic outcome
- what happens once you get to point of action
pharmacology steps
dose -> blood concentration -> receptor site concentration -> pharmacological response -> clinical response therapeutic outcome
physiological receptors
= subset of drug receptors defined by two properties
- Recognition: binds ligands reversibly with high affinity and specificity
- Transduction: structure-dependent conversion of binding into cellular response, reflected in activity or efficacy
steps starting with binding
binding -> transduction -> response (cell response -> organ response -> body response)
classical receptor theory
1: 1 between agonist concentration and % binding or max response
- can be true for some measured response like when recording current flow through ligand, gated ion channel
modified classical theory
-bc of signal transduction cascades the original activated receptor response can be amplified and a maximum response can be produced w/o full occupation (saturation) of receptor
result of modified classical theory
EC50 lower than apparent Kd for brining
why can cell amplify
because response is downstream from binding so cell can amplify the response amplification meaning separation between binding event and response event so can get full response w/o activation all response
full agonist
agonist that produces maximum response from a tissue
partial agonist
agonist that produces less than the maximum tissue response at full saturation
- binds at higher affinity which doesn’t interfere with its ability to activate
Efficacy
- reflects ability to convert to activated state; related to max response
- determined by extent of conversion of receptor to activated state by agonist
partial agonist efficacy
convert less of bound receptor to activated state and thus produce lower maximum response
potency
reflected by Ec50
- determined by binding affinity
- concentration dependence, high potency = high affinity
antagonist efficacy and potency
has zero efficacy but has potency bc bind with affinity but doesn’t lead to change
partial agonists are also
partial antagonists bc in presence of full agonist higher concentration of partial agonist will decrease response until maximum response of partial agonist is reached if the concentration of partial agonist vs full agonist is high enough
partial agonists therapeutic uses
use partial agonist which turns system down not off bc partial agonists block full response of full agonist
biased agonism
multiple independent responses can be generated from different conformations of the receptor; structurally diff agonists can produce diff functional effects by inducing different fxnional effects by inducting diff receptor conformations and activating different intracellular signaling pathways; receptors activating secondary messenger systems can activate more than one effector pathway; different agonists can activate pathways differentially with bias for one pathway over another
- especially true for GPCRs
opiate receptors and bias agonism
opiate receptors act by activating Gi/o and binding arrestin Gi/o = analgesic arrestin can -> respiratory distress; hope is find conformation that favors Gi/o to get analgesic effect without as much respiratory distress
competitive antagonist
increase the EC50 of agonist w/o affecting its maximum response
- occupy receptor w/o activation and decrease apparent potency of agonist (bc can only have one thing bound at a time); dnt affect efficacy of agonist just potency, increase concentration agonist to overcome this
- can be overcome with higher concentration of agonist and therefore maximum response to agonist is still attainable but requires higher concentrations of agonists
inverse agonist
decrease the resting or basal activity of receptor by converting receptors that are active under resting conditions to inactive state; occurs only for receptor that display constitutive activity but even in absence of constitutive activity inverse against will reduce response to an agonist
inverse agonist and basal activity
reduces basal activity binds to receptor and changes activity of receptor when there is no ligand;
add competitive agonist to basal receptor activity ->
no change
2 state model
basal activity equilibrium between active and inactive conditions generally most receptors = inactivated but some receptors in basal activity state in absence of ligand
agonist pulls to
activated state (have higher affinity for activated state than resting, inactive state)
