Pharmacodynamics Flashcards
pharmacology
study of drugs that interact with living beings through chemical processes
pharmacodynamics
drugs acting on body
pharmacokinetics
body acting on drug (metabolism)
receptors
interacts with drug and initiates the biochemical events leading to effects
physiological receptor
receptor for something naturally made in body (muscarinic, adrenergic)
agonists
activate receptor
antagonists
block endogenous ligand
negative or positive allosteric modulator
endogenous ligand to be weaker / stronger (bind somewhere else besides active site)
generalized receptors
not normally a receptor, drug binds to it and alters function (voltage-gated Na+ channels)
how do drugs bind to receptors?
hydrogen bonds
what can be drugs
anything that produces a physiological effect (most small molecules)
large amount of drugs deviate (biologics)
ligand gated ion channels
channel opens (allow ions to pass) when signaling molecule binds
G-protein coupled receptors
activates G protein with activate secondary messenger (cAMP) cascades
enzyme-linked (receptor tyrosine kinase)
activates signaling cascades through phosphorylation of substrates
nuclear receptor
steroid hormone are lipid soluble - allows to enter cell through lipid bilayer
activates or inhibits gene expression after binds to response elements
other receptors
no endogenous molecule acts on them, but affected by drugs
ex. proton pump, voltage gated ion channels, enzymes
physical properties of drug and structure determine (3 things)
binding
selectivity
affinity
selectivity
1 or many receptors
NOT ideal conditions of selectivity
bind to same receptor in multiple organs
bind to different receptors, especially when drug concentration in creases (more undesirable side effects)
when are drugs more specific?
at low concentrations
affinity
how readily and tightly does it bind
high affinitiy
good drug receptor interaction, less drug needed to produce a response
low affinity
poor drug receptor interaction, more drug needed to produce a response
affinity is measured through
equilibrium dissociation constant (Kd)
equilibrium dissociation constant
drug concentration for which 50% of that receptor is bound by the drug
lower Kd
higher affinity
higher Kd
lower affinity
law of mass action
drug effects are reversible interactions - can tilt equilibrium
when drug receptor complex is activated
conformational change
potency
how much drug needed to produce certain effect
efficacy
how big is the effect
quantal dose response
yes or no situation
therapeutic index
want high, so likelihood of toxicity is not reachable
margin of safety
the higher the TI of MOS, the safer the drug
antagonists
bind to receptor but don’t cause conformational change or biological response
competitive antagonist
more drug necessary to achieve effect (surmountable)
-compete for active site but doesn’t activate it
-decrease in potency but no decrease in efficacy
noncompetitive antagonist
antagonist that bind covalently (insurmountable)
-irreversibly bind to allosteroic site on receptor to prevent activation of receptor
-decrease in efficacy
partial agonist
can’t achieve 100%
decrease effects of full agonist when given together
inverse agonists
promotes inactive conformation - produce opposite effects of regular agonists
allosteric modulators
bind to secondary, allosteric site to + or - regulate agonist binding / efficacy
orthosteric drugs
bind to primary agonist site on receptor (no effect on signalling)
tachyphylaxis
decrease response when same does is given repeatbly
desensitization
receptor phosphorylated and binds B-arrestin
inactivation
receptor removed from membrane (reversible)
membrane forms endosome so receptor is embedded in it can lead to degradation
pharmacodynamic tolerance
chronic exposure to agonist can cause decrease in receptor number due to degradation of receptor or decrease in gene expression
upregulation
greater receptor number
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