Intro to Pharmacodynamics Flashcards
What is pharmacodynamics?
“what the drug does to the body”
How are receptors strictly defined?
Proteins that normally serve as receptors for endogenous LIGANDS (ex: hormones, NTs, growth factors, cytokines)
How are drug receptors broadly defined today?
any cellular constituent ex: enzymes, cell mbs, transport prots, structural prots, DNA, & RNA
what are agonists?
drugs that bind to receptors & mimic effect of the endogenous ligand
what are antagonists?
drugs that bind to receptors and produce no response (inhibit effect of the endogenous ligand). antagonists can be competitive or noncompetitive
What is a partial agonist?
drugs that bind to the receptor & produce a lesser effect than the endogenous ligand
What is classical receptor theory?
reversible interaction btwn drug (D) & receptor (R) follows law of mass action & is represented by:
[D] + [R] ,<-> [DR] -> effect
-where [DR] is concentration of activated drug-receptor complexes
What are dose-response relationships primarily used for?
To compare drug potencies & efficacies & to determine drug safety.
what are the two main types of dose-response relationships?
- graded
- quantal
all dose-response relationships are plots of?
dose on the independent (x) axis & response on the dependent (y) axis
What are graded dose-response relationships?
- show responses of INDIVIDUALS & are continuous responses
- Y axis is usually “percent response” from 0 to 100%
- provides info about INTENSITY OF RESPONSE over a dose range
What are quantal dose-response relationships?
- show POPULATION responses & are “all-or-none” responses
- Y axis is usually “ percent of individuals responding” from 0 to 100%
- provides info about # OF PATIENTS EXHIBITING A SPECIFIED EFFECT over dose range
What are graded response curves used mainly for?
to compare potency & efficacy
What are quantal response curves used mainly for?
to determine drug safety
Most patients respond to an average dose, those that dont?
- patients that require a lower dose is often due to ADME
- patients that require a higher dose is often due to things like drug tolerance
What is potency?
Potency is a R or L shift on the dose-response curve graph; a drug is more potent if it takes less of that drug to get the desired response
What is efficacy?
an up or down shift on the dose-response curve graph; a drug is more efficacious if at it’s max it can get a higher % maximal effect than another drug
What is EC50 or ED50?
concentration or dose causing a 50% maximal response; it is used to characterized drugs & compare potencies
What else can dose-response curves be used to determine?
Any effective dose (ED1, ED10, ED99) or can be used to determine toxic doses (TD) or lethal doses (LD)
What is the therapeutic index (TI)?
TI = TD50/ED50 (or LD50/ED50); want it to be really large, so there is a wide range btwn safe dose & dose that causes death
What is the margin of safety?
= TD1/ED99 (or LD1/ED99); margin of safety is more conservative measure of drug safety than therapeutic index b/c it is essentially the ratio of drug dose that causes toxicity/death in 1% of pop to drug dose that causes desired therapeutic effect in 99% of the population
upon continuous exposure to a drug, what can happen to receptors?
They can become DESENSITIZED (usually due to downregulation) which is 1 reason for drug tolerance & need for “drug holidays”;
what is an example of receptor desensitization?
desensitization of B-adrenergic receptors due to downregulation (decreased receptor concentration - body downregulates receptors in response to drug, so more drug is required to get the same response in future)
What can occur due to increased receptor concentration?
upregulation or sensitization (this is rare)
modern molecular tools have resulted in the discovery of…
… many receptor subtypes, where only a single type was previously thought to exist
Why do so many receptor subtypes occur?
TISSUE SPECIFICITY & SELECTIVITY - which allows the same endogenous signaling agent to act in different tissues
our expanding knowledge of receptor subtypes is providing what?
new avenues of drug development
What is an orphan receptor?
a receptor w/ no known endogenous ligand
What is a classic example of an orphan receptor?
opioid receptors identified using morphine as agonist
What is a newer example of an orphan receptor?
cannabinoid receptors identified using THC as agonist
What do we now know about opioid and cannabinoid receptors?
that there are indeed endogenous opioids (ex: endorphins) that are involved in analgesia & euphoria, & endogenous cannabinoids that are involved in analgesia, sleep, & hunger
Several other orphan receptors have been discovered and are what?
the focus of new pharmaceuticals
