U2.2 DRG CONCENTRATION & RESPONSE : GDRC Flashcards
Response of a particular receptor-effector system is measured against increasing concentration of a drug
Graded-Dose Response Curve
Graph of the response versus the drug dose
Graded-Dose Response Curve
derived from Graded Dose-Response Curve
Efficacy (Emax) and potency (EC50)
↓ EC50, ___ potency
↑ potency
Maximal response that can be produced by a drug
MAXIMAL EFFICACY (Emax)
T/F In Emax all receptors are occupied
T
Measured with a graded dose-response curve but not with quantal dose-response curve
Emax
Concentration of drug that produces 50% of maximal effect
EC50
drug dose will be half saturate the receptors and achieve for half the efficacy (at equilibrium)
EC50
amount of drug needed to produce a given effect
Potency
Total number of receptor sites
Bmax
All receptors have been occupied
Bmax
Equilibrium dissociation constant
KD
Concentration of the drug required to bind 50% of the
receptors
KD
Difference of EC50 and KD
EC50 - response
KD - receptors
___ KD, ↑ drug affinity to receptor / binding affinity
↓ KD
___ affinity drugs = ↓ binding affinity
↓ affinity drugs
Paramters:
Emax
EC50
KD
Emax - efficacy
EC50 - potency
KD - affinity
Agonist response in the absence of antagonist = ____ potency
↑ drug potency
Transduction process between the occupancy of receptors and production of specific effect
COUPLING
Highly effective coupling can be elicited by a full agonist and spare receptors
COUPLING
Maximal drug response is obtained at less than maximal
occupation of the receptors
Spare Receptors
T/F Spare receptors are qualitatively different from non-spare receptors, not hidden or unavailable
False, not qualitatively different (same receptor pool)
T/F Spare Receptrs are temporal in character, when occupied, they can be
coupled to respond, there is still effect
True
T/F Drugs with low binding affinity for receptors will be able to
produce full response event at low concentration
True
KD drug amount (</>) EC50 with spare receptors
KD drug amount > EC50 with spare receptors
T/F Drugs with low binding affinity for receptors will be able to
produce full response event at low concentration
True
T/F Spare receptors cant compare concentration for 50% of maximal effect (EC50
with concentration for 50% maximal binding (Kd)
False, it can compare
T/F Actual number of receptors may exceed the number of
effectors available
True
Binding with these molecules will result to no detectable change/response in the function of the biologic system
Inert Binding Sites
Non-regulatory molecules of the body to which drugs can attach to
Inert Binding Sites
Binds to the receptor and directly or indirectly bring about an effect
Agonist
bind to receptor and bring full activation
Full agonist
Produces less than the full effect, even when it has saturated the receptors
Partial Agonist
Acts as an inhibitor in the presence of a full agonist
Partial Agonist
Binds but do not activate the receptors
Antagonist
Blocks or competes with agonist - whether full or partial agonist
Antagonist
Type of Agonist
Competes with agonist receptor - same binding site
Competitive Antagonist
Type of Antagonist
Binds to the receptor reversibly without activating the effector system
Competitive Antagonist
T/F In competitive antagonist, antagonist increases the agonist concentration needed for
a given degree of response
True
Effects of competitive antagonist can be overcomed by (increasing/decreasing) agonist
increasing
Type of antagonist
Same maximal effect is reached
Competitive Antagonist
T/F Degree of inhibition produced by the competitive
antagonist depends on the concentration of antagonist
True
T/F Clinical response to a competitive antagonist does not depend on
the concentration of agonist that is competing for binding
to the receptor.
False, it depends on the concerntration of the agonist
Type of Antagonist
Binds with the receptor via covalent bonds
Irreversible Antagonist
Type of Antagonist
Receptor is not available to bind the agonist
Irreversible Antagonist
Type of Antagonist
Duration of action is relatively independent
Irreversible Antagonist
Type of Antagonist
phenoxybenzamine binding with alpha receptors
Irreversible Antagonist
T/F With an irreversible antagonist, Emax will not be reached, no increase in median effective dose unless there are special receptors
True
T/F With an irreversible antagonist, there is an increase in median dose (ED50) when there are spare receptors
True
Type of Antagonist
Does not depend on interaction with the agonist’s receptor
Chemical Antagonist
Type of antagonism that do not involve a receptor at all
Chemical Antagonist
Type of antagonist
Protamine counteracts the effect of heparin
Chemical Antagonist
Type of antagonist
Drug that interacts directly with the drug being antagonized to remove it or to prevent it from reaching its target
Chemical Antagonist
Type of antagonist
Makes use of the regulatory pathway (separate regulatory pathway)
Physiologic Antagonist
Type of Antagonist
Effects that are less specific and less easy to control
Physiologic Antagonist
Type of Antagonist
Glucocorticoids and Histamine
Physiologic Antagonist
Response gradually, have a diminishing response to a certain drug after an initial high level of response so usually this would be idiopathic
Receptor Desensitization
T/F During receptor desensitization the reason for its effect is still unknown.
True
Cells use more than one signaling mechanism to respond to the drug
Structure Activity Relationship
↑ competitive antagonist, _____ agonist concentration
↑ agonist concentration
↑ EC50 =_____
drug concentration
↑ drug concentration
↑ EC50, ↑
drug concentration = ___ potency, ____ affinity
↓ potency, ↓ affinity
↑ noncompetitive antagonist = ___ Emax (efficacy)
↓ Emax
T/F With spare receptors, Emax (maximal effect) is already achieved even without reaching the Bmax (all receptors).
True
