Week 4: Pharmodynamics- Nordgren Flashcards
(45 cards)
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
