Week 5 Material
What is the physiological mechanism underlying the differential efficacies of full and partial
agonists?
Agonists may be referred to as a ligand that binds to receptors and produces a biological
response at a more amplified level. There are full agonists and partial agonists.
o Full agonists include a large stimulus to cellular signaling machinery, resulting in
a larger conformational change and receptor activation associated with triggering
biological pathways with LARGE effects.
o Partial agonists include a small stimulus to cellular signaling machinery, resulting
in a smaller conformational change and receptor activation associated with
triggering biological pathways with SMALL effects.
Overall, partial agonists are drugs/ligands that bind to and activate a given receptor, but
have only partial efficacy at the receptor relative to a full agonist.
Citation:
Week 5 Pharmacodynamics Lecture, slide 22-23
Describe post-binding effects of an agonist to a GPCR that’s coupled to adenylyl cyclase.
When an agonist binds to a G-protein-coupled receptor (GPCR) that's linked to adenylyl
cyclase (AC), the following effects occur in the adenylyl cyclase pathway:
o The activation of ATP causes increased cyclic AMP (cAMP) production: When
an agonist activates a GPCR that's linked to the Gαs protein, the production of
intracellular cAMP levels increases.
o Activation of phosphorylate kinase (protein kinase A or PKA): The activated G
alpha proteins increase PKA production. The catalytic components then break off
and are disassociated.
o This process phosphorylates proteins into Protein PO4.
o Activation of cAMP-responsive element-binding protein (CREB): PKA activates
CREB, which modulates gene transcription in the nucleus.
Citation:
Week 5 Pharmacodynamics Lecture, slide 41-42
Identify the receptor type that mediates the fastest cellular responses and relate its function to the
response speed.
The receptor type that mediates the fastest cellular responses is the ligand-gated ion
channel receptor (also known as ionotropic receptor), which functions by directly
opening an ion channel upon ligand binding, allowing rapid influx or efflux of ions,
leading to an almost immediate change in membrane potential and cellular response.
These high conductance, ligandgated ion channels usually permit passage of Na+ or Cl−
while K+and Ca2+ are involved less frequently. It directly opens the channel pore when a
ligand binds, allowing ions to flow across the cell membrane almost instantaneously.
In the presence of an appropriate neurotransmitter, the channel opens rapidly to a high-
conductance state, remains open for about a millisecond, and then closes. This causes
causing a quick electrical signal transmission across the synapse.
Citation: Goodman & Gilman's: The Pharmacological Basis of Therapeutics textbook, page 312
This study source was downloaded by 100000899194722 from CourseHero.com on 05-30-2025 10:59:55 GMT -05:00
https://www.coursehero.com/file/249946547/Discussion-1docx/
, Differentiate competitive and noncompetitive antagonists effects on agonist LDR curves binding
and explain the mechanism underlying these differential effects.
The competitive antagonist lowers the potency of the agonist but does not alter its
efficacy. A competitive (reversible) antagonist competes to occupy the same receptor
site.
o The effect of a competitive (reversible) antagonist on agonist LDR curve is a shift
to the right (since it takes more dose to get the same effect) and the shape is
parallel (to get the maximum effect).
A noncompetitive antagonist binds to other components of the receptor to diminish or
eliminate the effect of the drug binding to the receptor. A noncompetitive (irreversible)
antagonist competes to occupy a different part of the receptor site.
o The effect of a noncompetitive (irreversible) antagonist on agonist LDR curve is a
shift down and the shape becomes more linear (flat) since it decreases the
efficacy of the agonist
Citation: Week 5 Pharmacodynamics Lecture, slide 26-28
When selecting a drug, is potency or efficacy more important and why?
Potency is the concentration (EC50) or dose (ED50) of a drug required to produce 50% of
that drug’s maximal effect. It is an expression of the activity of a drug, in terms of the
concentration or amount needed to produce a defined effect. Potency of a drug depends
on the affinity of the receptors to bind the drug and how effectively the drug-receptor
interaction leads to clinical response
Efficacy (Emax) is the maximum effect which can be expected from this drug (i.e. when
this magnitude of effect is reached, increasing the dose will not produce a greater
magnitude of effect). Efficacy depends on the concentration at the site of action, the
number of drug-receptor binding, psychological factors and, the efficiency of the
coupling of receptor activation to cellular responses
Overall, when selecting a drug, efficacy is more significant than potency. A drug with
greater efficacy than greater potency is more therapeutically beneficial. The clinical
effectiveness of a drug depends on its efficacy as it provides a decisive component in
choosing a drug among other drugs of the same kind. On the other hand, potency may
instead be more beneficial as a decisive component in choosing the dose of the drug.
Citation: Week 5 Pharmacodynamics Lecture, slide 8-11
What is a possible advantage of administering a drug that is composed of the active enantiomer
versus a racemic mixture?
A stereoisomer is a drug with an active isomer and an inactive isomer. Both isomer types
have the same chemical structure but different spatial arrangements or complimentary fits
such that one remains active and one remains inactive upon binding to the desired
receptor.
This study source was downloaded by 100000899194722 from CourseHero.com on 05-30-2025 10:59:55 GMT -05:00
https://www.coursehero.com/file/249946547/Discussion-1docx/
What is the physiological mechanism underlying the differential efficacies of full and partial
agonists?
Agonists may be referred to as a ligand that binds to receptors and produces a biological
response at a more amplified level. There are full agonists and partial agonists.
o Full agonists include a large stimulus to cellular signaling machinery, resulting in
a larger conformational change and receptor activation associated with triggering
biological pathways with LARGE effects.
o Partial agonists include a small stimulus to cellular signaling machinery, resulting
in a smaller conformational change and receptor activation associated with
triggering biological pathways with SMALL effects.
Overall, partial agonists are drugs/ligands that bind to and activate a given receptor, but
have only partial efficacy at the receptor relative to a full agonist.
Citation:
Week 5 Pharmacodynamics Lecture, slide 22-23
Describe post-binding effects of an agonist to a GPCR that’s coupled to adenylyl cyclase.
When an agonist binds to a G-protein-coupled receptor (GPCR) that's linked to adenylyl
cyclase (AC), the following effects occur in the adenylyl cyclase pathway:
o The activation of ATP causes increased cyclic AMP (cAMP) production: When
an agonist activates a GPCR that's linked to the Gαs protein, the production of
intracellular cAMP levels increases.
o Activation of phosphorylate kinase (protein kinase A or PKA): The activated G
alpha proteins increase PKA production. The catalytic components then break off
and are disassociated.
o This process phosphorylates proteins into Protein PO4.
o Activation of cAMP-responsive element-binding protein (CREB): PKA activates
CREB, which modulates gene transcription in the nucleus.
Citation:
Week 5 Pharmacodynamics Lecture, slide 41-42
Identify the receptor type that mediates the fastest cellular responses and relate its function to the
response speed.
The receptor type that mediates the fastest cellular responses is the ligand-gated ion
channel receptor (also known as ionotropic receptor), which functions by directly
opening an ion channel upon ligand binding, allowing rapid influx or efflux of ions,
leading to an almost immediate change in membrane potential and cellular response.
These high conductance, ligandgated ion channels usually permit passage of Na+ or Cl−
while K+and Ca2+ are involved less frequently. It directly opens the channel pore when a
ligand binds, allowing ions to flow across the cell membrane almost instantaneously.
In the presence of an appropriate neurotransmitter, the channel opens rapidly to a high-
conductance state, remains open for about a millisecond, and then closes. This causes
causing a quick electrical signal transmission across the synapse.
Citation: Goodman & Gilman's: The Pharmacological Basis of Therapeutics textbook, page 312
This study source was downloaded by 100000899194722 from CourseHero.com on 05-30-2025 10:59:55 GMT -05:00
https://www.coursehero.com/file/249946547/Discussion-1docx/
, Differentiate competitive and noncompetitive antagonists effects on agonist LDR curves binding
and explain the mechanism underlying these differential effects.
The competitive antagonist lowers the potency of the agonist but does not alter its
efficacy. A competitive (reversible) antagonist competes to occupy the same receptor
site.
o The effect of a competitive (reversible) antagonist on agonist LDR curve is a shift
to the right (since it takes more dose to get the same effect) and the shape is
parallel (to get the maximum effect).
A noncompetitive antagonist binds to other components of the receptor to diminish or
eliminate the effect of the drug binding to the receptor. A noncompetitive (irreversible)
antagonist competes to occupy a different part of the receptor site.
o The effect of a noncompetitive (irreversible) antagonist on agonist LDR curve is a
shift down and the shape becomes more linear (flat) since it decreases the
efficacy of the agonist
Citation: Week 5 Pharmacodynamics Lecture, slide 26-28
When selecting a drug, is potency or efficacy more important and why?
Potency is the concentration (EC50) or dose (ED50) of a drug required to produce 50% of
that drug’s maximal effect. It is an expression of the activity of a drug, in terms of the
concentration or amount needed to produce a defined effect. Potency of a drug depends
on the affinity of the receptors to bind the drug and how effectively the drug-receptor
interaction leads to clinical response
Efficacy (Emax) is the maximum effect which can be expected from this drug (i.e. when
this magnitude of effect is reached, increasing the dose will not produce a greater
magnitude of effect). Efficacy depends on the concentration at the site of action, the
number of drug-receptor binding, psychological factors and, the efficiency of the
coupling of receptor activation to cellular responses
Overall, when selecting a drug, efficacy is more significant than potency. A drug with
greater efficacy than greater potency is more therapeutically beneficial. The clinical
effectiveness of a drug depends on its efficacy as it provides a decisive component in
choosing a drug among other drugs of the same kind. On the other hand, potency may
instead be more beneficial as a decisive component in choosing the dose of the drug.
Citation: Week 5 Pharmacodynamics Lecture, slide 8-11
What is a possible advantage of administering a drug that is composed of the active enantiomer
versus a racemic mixture?
A stereoisomer is a drug with an active isomer and an inactive isomer. Both isomer types
have the same chemical structure but different spatial arrangements or complimentary fits
such that one remains active and one remains inactive upon binding to the desired
receptor.
This study source was downloaded by 100000899194722 from CourseHero.com on 05-30-2025 10:59:55 GMT -05:00
https://www.coursehero.com/file/249946547/Discussion-1docx/
