Lecture 3 - Pharmacodynamics (Ligands) Flashcards
what is a ligand?
a substance/drug that binds to a receptor and influences its activity
ligands can be ____ or ____ to a receptor
agonists or antagonists
substances that the body makes which has a physiological effect (typically agonists)
endogenous ligand
a substance/drug that binds to and activates a receptor to produce a biological response
an agonist
an agonistic response is usually depicted as a:
concentration response curve (or dose-response curve)
refers to the concentration of drug that yields a 50% maximal effect
EC50 (effective concentration 50)
the maximal biological effect observed with the dose response
Emax
how do you calculate the effect for a given concentration of a drug?
E = ((Emax)[drug]) / ([drug] + EC50)
the formula used to calculate the effect of a drug is identical to the formula for:
the law of mass action
what is the implication when [drug] = EC50?
a half-maximal effect of the drug is observed (Emax/2)
a term that refers to the concentration dependence (Emax)
efficacy
a term that refers to the concentration dependence (EC50)
potency
a drug with strong potency has a low:
EC50 (only a small concentration is required to generate a large effect)
a drug with weak potency has a high:
EC50
a _____ can generate the maximal observed effect
full agonist
a _____ can generates a sub maximal effect, regardless of dose
partial agonist
an _____ causes suppression of basal activity
inverse agonist
can endogenous ligands be inverse agonists?
no
true or false: agonists can vary in both efficacy and potency
true
drugs with different _____ exhibit different concentrations required for a particular effect
potency
drugs with different _____ exhibit a difference in the maximal effect that can be achieved
efficacy
a type of receptor ligand that blocks a biological response by binding to and blocking receptors rather than activating them
antagonist
antagonists can be either _____ or _____
competitive, non-competitive
a compound that occupies the same binding site as the agonist, but does not exhibit a biological response
competitive antagonist
what is a surmountable antagonist?
at high enough concentrations, the antagonist is displaced, and maximal efficacy can be achieved
what is the “dose ratio” of a schild plot?
the ratio of agonist EC50 in the presence vs. absence of antagonist
what is the formula for the dose ratio?
dose ratio = (agonist EC50 (with antagonist)) / (agonist EC50 (no antagonist))
what is the x-intercept of the schild plot?
called the pki and it reflects the potency of the antagonist
the highest concentration of antagonist which has no effect on agonist activity
pki
the higher the pki, the more:
potent the drug
increasing the concentration of a partial agonist while keeping the full agonist at a constant concentration will lead to:
a reduced response as the concentration of the partial agonist increases
like competitive antagonists, partial agonists will lead to a _____ shift in the full agonist _____, but will not affect _____
rightward, potency (larger EC50), efficacy (same Emax)
what is irreversible competitive antagonism?
the antagonist binds irreversibly to the drug binding site and cannot be displaced by increasing agonist concentration
what effects does irreversible non-competitive antagonism have on efficacy and potency?
reduced agonist efficacy, but no effect on potency
activate or inhibit a receptor by binding to a site distinct from the primary (orthosteric) site
allosteric ligands
what is non-competitive inhibition?
antagonist binding at a distinct site from the agonist (an allosteric site) which prevents activation of the receptor
drugs that have an allosteric effect that acts to potentiate/enhance the effects of an agonist
positive allosteric modulators
what effects do positive allosteric modulators have on efficacy?
increased efficacy or potency, or both
alcohol is a positive allosteric modulator at which receptor?
the GABAa receptor
what is the effect of alcohol on the GABAa receptor?
it enhances the effect of the inhibitory neurotransmitter GABA (you need less GABA to bind to the GABAa receptor)
drug receptor interaction is determined by:
1) binding of the ligand to the receptor
2) generation of a biological response
in most cases, ligand binding is reversible, so receptors continuiously switch between:
occupied and unoccupied states
how well and how long a ligand occupies a receptor is dictated by its:
affinity
drug affinity is represented by the:
equilibrium dissociation constant (Kd)
affinity is governed by:
electrochemical properties of the receptor and ligand
a measure of drug-receptor affinity and efficacy
potency
a measure of how well a drug activates a receptor
drug efficacy
unlike potency, efficacy is independent from
drug affinity
true or false: there is not always a direct relationship between drug effect and drug binding
true
why can there be this mismatch between drug binding and drug effect?
one reason is that there may be more receptors present than are required for activation of a full biological effect
having more receptors than is needed to produce a maximal biological effect
receptor reserve
when receptor reserve is observed, application of small concentrations of an irreversible antagonist does not:
reduce the maximum biological effect (need lots of antagonist to reduce the effect)
when receptor reserve is observed, it indicates there is a:
surplus of receptors
true or false: receptor reserve is always observed
false
receptor binding (affinity) and effect (Emax) are related, but not always:
equal
