what role does it play?
initiates what events?
interacts with a drug and initiates the biochemical events leading to drug effect
Drug-Receptor Interaction--> Covalent
-can it be reversed?
Irreversible and reactivation requires resynthesis of the receptor or enzymatic removal of the drug
Drug Receptor Interaction--> Noncovalent
-is it reversible?
reversible, most drugs bind to receptors via non-covalent bonds
Strongest to weakest drug receptor interactions
Ionic>hydrogen>hydrophobic>Van der waals
drug dose on the x axis
drug effect on the y axis
how do you get a sigmoidal dose response curve?
-x, vs y axis
log of drug dose on x
response on y
more common than hyperbolic curve
The maximal effect that can be produced by the drug
The dose of the drug that produces 50% of its maximal effect
Graded Response curve:
-what question does it answer?
-What varies continuously?
-represents mean value of what?
Answers the question how much
magnitude of a response varies continously
typically represents the mean value within a population or a single subject
-question it answers
-type of response
-used for what?
all or none; yes-no binary response
-does the response occur or not?
-in how many?
-requires a pre-defined response (death, falling asleep, 10% reduction in bp)
-used to examine the frequency of the number of individuals showing a response within a large population
non-cumulative quantal dose-response curve
number or percent of individuals responding at a certain dose of a drug and only at that dose
Cumulative quantal dose response curve
number or percent of individuals responding at a certain dose of a drug AND at all doses lower than that dose
-meaning of the value?
higher the TI the safer the drug
range of doses of a drug or of its concentration in a bodily system that provides for the safe and effective therapy
-meaning of this value
-low vs high
KD is the equilibirum dissociation constant, which is the drug concentration at which 50% of the drug receptor binding sites are occupied by the drug
-unit is molar concentration
-lower the value, higher the affinity of a drug for a receptor
Where [L], [R] and [LR] represent molar concentrations of ligand, receptor, and their complex
What is the EC50
-how is it different than KD
-It is simply the concentration of agonist required to provoke a response halfway between the baseline and maximum responses. Because the EC50 defines the location of the dose-response curve for a particular drug, it is the most commonly used measure of an agonist’s potency.
-However, the EC50 is usually not the same as the Kd for the binding of agonist to its receptor -- it is not a direct measure of drug affinity.
-Magnitude of a drug's effects will be proportional to what?
proportional to the degreee of its interaction with a receptor
- property of a drug determined by its affinities at various binding sites
-measured by comparing affinities of a drug to different receprots
-a more selective drug would affect fewer targets over a specific concentration range (therapeutic range)
ability of a drug to change a receprot function and produce a physiological response upon its binding to a receptor
-definition, does it have intrinsiv activity?
bind to the receptor and stabilize it in a particular conformation (usually active), producing a physicological response
*have an intrinsic activity*
-define, does it have intrinsic activity?
-effect in absence of an agonist?
-receptor antagonists bind to the receprot but do not change its function. however, they prevent activation of the receport in the presence of an agonist
-don't have intrinsic activity
-don't change function of receptor upon binding
-no pharmacological effect in the absence of an agonist
-when do they produce maximal pharm. effect?
-intrinsic activity levels?
fully activate receptors producing a max pharm effect when all receptors are occupied
-maximal intrinsic activity
-describe activation of receptor
partially activate the receptor upon binding
-produce a sub-maximal pharm effect when all receptors are occupied
-intrinsic efficacy varies depending on drug, but ALWAYS submaximal
-effect on receptor signaling
-constitutive receptor activity?
-intrinsic activity, why?
-decrease receptor signaling
-decrease response at receprotrs with a significant level of constitutive receptor activity
-intrinsic activity is present and related to the inhibition of receptor function
Pharm: (receptor) antagonism action at the same receptor as endogenous ligands or agonist drugs
Chemical: when chemical antagonist makes the other drug not available
Physiologic: occurs between endogenous pathways regulated by different receptors
-compete with what?
-can be displaced by what
-compete with endogenous chemicals or agonist drugs for binding to the receptor
-can be displaced from the receptor by other drugs (effects are surmountable)
types, define (x2)
-receptor inactivation is not surmountable
Irreversible antagonists: irreversibly bind to and occlude the agonist site on the receptor by forming covalent bonds
Allosteric antagonists: bind to a site other than the agonist site to prevent or reduce agonist binding or activation of the receptor
-EC50 increases, Emax does not change
-effect on EC50
-effect on Emax
EC50 does not change, but Emax decreases
-what drugs tend to be more potent
-what value represents drug potency? (lower vs higher)
-Potency describes the amount of drug required to produce a specific pharmacological effect
-drugs with higher affinities for a receptor--> lower KD tend to be more potent
-potency describes the amount of drug required to produce a specific effect and is represented by the ED50--> the lower the value, the more potent
*determines the drug dose that will be used clinically*
-represented by what value?
-efficacy is related to total number of?
-determines clinical what?
-describes the maximal pharmacological effect the drug can produce
-represented by the Emax, the greater the Emax the more efficacious the drug
-efficacy is related to the total number of receptors available to bind a drug, and it determines the clinical effectiveness of a drug
Describe increasing potency vs increasing efficacy graphs
1/1000th of a milligram, which is 1/1000th of a gram
1 kg = how many pounds?
-tsp, tbsp, ounce, cup
-quart=how many ml? how many pints in quart?
-pint=ml? how many oz in one pint?
-gallon=how many L? quarts in a gallon? pints in gallon?
Dosing Frequency abbreviations:
Routes of administration:
Routes of administration:
-to run at
-keep vein open
# of gms in 100ml