pharmacodynamics Flashcards
Dose- response relationship
relationship between size of an administered dose and intensity of response produced
What does graded dose response mean
as dose increases, response becomes progressively larger
maximal efficacy
largest EFFECT drug can produce
- for the SAME doses, which drug has the LARGER EFFECT
How is maximal efficacy indicated on a dose response curve
the height of a curve
what is a problem with high efficacy when treating a patient?
it is hard to match the response intensity to patient needs
Relative Potency
AMOUNT of drug required to elicit an effect
- how much drug do we need to elicit the same effect
what are 3 points about potency
(1) rarely important drug characteristic
(2) Implies nothing about Maximal efficacy
(3) “this drug produces its effect at low doses”
Receptors
chemical sites in body that most drugs interact with to produce its effect
Equation for interaction between a drug and receptors
D + R <– –> D - R COMPLEX –> RESPONSE
D= drug
R= receptors
binding of a drug is reversible
receptor can only be on or off
what happens when a drug binds to a receptor?
mimic or block actions of endogenous regulatory molecules
- increase of decrease activity controlled by receptor
what do drugs do for the body
help the body help itself
what are the 4 primary receptor families
a) cell- membrane embedded receptor
b) ligand- gated ion channels
c) G protein- coupled receptor systems
d) transcription factors
Cell-membrane embedded receptors
- spans cell membrane
- ligand-domain located on cell surface
- enzyme catalytic site located on inside of cell
what happens when a drug binds to cell-membrane embedded receptors?
how quickly does it respond
activates enzyme = increase activity
response occurs in seconds
what receptor does insulin use
cell-membrane embedded receptors
Ligand- Gated Ion Channel function
how fast does it happen
regulate ion flow in and out of cells
- specific to ion
milliseconds
what act through ligand-gated ion channels?
several neurotransmitters (acetylcholine and GABA)
G Protein -Coupled Receptor System components
- receptor
- G protein
- effector
G Protein- Coupled Receptor System function
how fast
drug/endogenous ligand activates receptor which activated G Protein –> activates effector
rapid response
Transcription factors
situated on DNA in nucleus
- activated by lipid-soluble ligands
how do transcription factors differ from the other
(1) receptors are within cell not on surface
(2) responses from activation are delayed –> because transcription of RNA
How fast does transcription factors act
hours or days
Selectivity
only elicit responses for which it is given
why is there no such thing as wholly selective drugs
all drugs cause side effects
what does it mean when a drug is more selective
fewer side effects because the drug reacts with fewer specific receptors for that drug.
what are there receptors for
(1) each neurotransmitter
(2) each hormone
(3) molecules that regulate physiological processes (histamine, prostaglandins, leukotrienes)
why is selective drug action possible
due to many types of receptors
if a drug only acts with one receptor and regulates one process
drug effect will be limited
if drugs interact with several receptors
drug will elicit a drug effect will be wide
can a drug selectively turn on single processes of a receptor?
no, if the receptor is activated ALL processes are activated.
Ex) opioid receptors modulate pain, but also respiration and bowel motility
- morphine for pain will also cause respiratory depression and constipation
does selectively guarantee safety
NO
EX) botulinum toxin selective for one receptor but causes paralysis of respiratory muscles –> death
what are the theories of drug- related interaction
(1) Simple Occupancy Theory
(2) Modified Occupancy Theory
Simple Occupancy Theory (SOT)
(1) intensity of drug response is proportional to number of receptors occupied by the drug
(2) maximal response will occur when all available receptors are occupied
What does SOT assume
all receptors are identical with
(1) ability to bind to receptor
(2) ability to influence receptor function
What factors does Modified theory take into account?
Affinity and Intrinsic activity
Affinity
is it reflected in efficacy or potency?
strength of attraction between drug and receptor
potency
- high affinity = effective at low doses = very potent
Intrinsic Activity
is it reflected in efficacy or potency?
ability of a drug to ACTIVATE a receptor
Efficacy
-high intrinsic activity cause intense receptor activation = high efficacy
- intensity of response is still related to number of receptors occupied
Antagonists
Drugs block action of endogenous molecules
- prevents activation of the receptors by agonist
Agonists
Drugs mimic action of endogenous molecules
- activate receptor (decreases or increases receptor activity depending on what the endogenous molecules does to the receptor)
does agonists have affinity or high intrinsic activity?
BOTH
- binds and activates
Explain how antagonist response is determined
Determined by how much Agonist is present
- if there is no agonist present, administering antagonist has no effect
Noncompetitive (insurmountable) Antagonists (NA
bind IRREVERSIBLY
- reduce number of receptors available for agonists
- reduces TOTAL number of receptors available for
- if enough NA is present, agonist effect will be completely blocked
Competitive (Surmountable) Antagonists (CA)
REVERSIBLY binds
- binding to endogenous molecules or CA is due to which is present in highest conc.
- MAX response of agonist is not reduced
–> increase amount of agonist required to produce a given intensity of response
Partial Agonists
- moderate intrinsic activity
- Maximal effect of a partial agonist is lower than that of a full agonist
What can happen to a cell that is subject to continuous activation/ inhibition
(1) can change number of receptors on their surface
(2) change sensitivity to agonist molecules
what happens when a receptor is continually exposed to an agonist
- will become less responsive (desensitized, refractory, or down-regulated)
- destruction of receptors
What happens to receptors with continuous exposure to antagonist
cell will become more responsive (hypersensitivity, supersensitive, up-regulated)
-synthesis of more receptors
what are examples of drugs that don’t involve receptors?
Antacids: neutralize gastric acidity by chemical reaction stomach acid
Antiseptics: precipitating bacterial proteins
Saline laxatives: draws water into intestinal lumen via osmotic effect
What is ED50
Average Effective Dose
The dose at middle frequency distribution
standard dose
Therapeutic Index (TI)
measure of drugs safety
ratio of drugs LD50 to ED50
LD50
the dose that is lethal to 50% of animals treated
