TEST BANK
Goodman and Gilman's The
Pharmacological Basis of Therapeutics
14th Edition
Author(s)Laurence Brunton; Bjorn Knollmann
Print ISBN: 9781264258079
,Question 1
A research team identifies an extract from a medicinal plant that
reduces inflammatory signaling in cultured cells. The extract contains
hundreds of chemical constituents. What is the most appropriate next
step in developing a drug lead from this observation?
A. Administer the crude extract to patients to determine the effective
dose
,B. Perform bioactivity-guided fractionation to identify the active
constituent(s)
C. Discard the extract because mixtures cannot yield drug candidates
D. Immediately perform computer-based docking of every compound in
the extract
Correct Answer:
B. Perform bioactivity-guided fractionation to identify the active
constituent(s)
Rationale:
Bioactivity-guided fractionation repeatedly separates an active extract
into fractions while testing each fraction for the desired biological
activity, allowing investigators to identify the molecule or molecules
responsible for the effect. A is inappropriate because an
uncharacterized mixture has uncertain composition, potency, toxicity,
and pharmacokinetics. C is incorrect because natural-product mixtures
can contain valuable lead compounds. D is premature because the
chemical identities and structures responsible for the activity have not
yet been established.
Question 2
Which characteristic makes a biologically active natural product
particularly useful as a starting point for drug discovery?
A. It is guaranteed to have acceptable oral bioavailability
B. It has already demonstrated a defined mechanism in humans
C. It provides a chemically active scaffold that can be optimized
D. It is always less toxic than synthetic compounds
, Correct Answer:
C. It provides a chemically active scaffold that can be optimized
Rationale:
Natural products can provide structurally diverse molecules with
biologic activity that serve as starting points for lead optimization. A is
incorrect because many natural products have poor absorption, rapid
metabolism, or other pharmacokinetic limitations. B is incorrect
because activity of a natural product does not establish its precise
human mechanism. D is incorrect because natural origin does not
guarantee safety.
Question 3
A purified plant-derived compound demonstrates promising
antibacterial activity but has very poor water solubility. Which approach
best reflects a rational drug-discovery strategy?
A. Abandon the compound immediately
B. Increase the dose until the desired concentration is reached
C. Modify the chemical structure to improve physicochemical properties
while preserving activity
D. Replace all biological testing with computational modeling
Correct Answer:
C. Modify the chemical structure to improve physicochemical properties
while preserving activity
Rationale:
A promising lead may require optimization of solubility, stability,
absorption, potency, or selectivity. Structural modification can improve
Goodman and Gilman's The
Pharmacological Basis of Therapeutics
14th Edition
Author(s)Laurence Brunton; Bjorn Knollmann
Print ISBN: 9781264258079
,Question 1
A research team identifies an extract from a medicinal plant that
reduces inflammatory signaling in cultured cells. The extract contains
hundreds of chemical constituents. What is the most appropriate next
step in developing a drug lead from this observation?
A. Administer the crude extract to patients to determine the effective
dose
,B. Perform bioactivity-guided fractionation to identify the active
constituent(s)
C. Discard the extract because mixtures cannot yield drug candidates
D. Immediately perform computer-based docking of every compound in
the extract
Correct Answer:
B. Perform bioactivity-guided fractionation to identify the active
constituent(s)
Rationale:
Bioactivity-guided fractionation repeatedly separates an active extract
into fractions while testing each fraction for the desired biological
activity, allowing investigators to identify the molecule or molecules
responsible for the effect. A is inappropriate because an
uncharacterized mixture has uncertain composition, potency, toxicity,
and pharmacokinetics. C is incorrect because natural-product mixtures
can contain valuable lead compounds. D is premature because the
chemical identities and structures responsible for the activity have not
yet been established.
Question 2
Which characteristic makes a biologically active natural product
particularly useful as a starting point for drug discovery?
A. It is guaranteed to have acceptable oral bioavailability
B. It has already demonstrated a defined mechanism in humans
C. It provides a chemically active scaffold that can be optimized
D. It is always less toxic than synthetic compounds
, Correct Answer:
C. It provides a chemically active scaffold that can be optimized
Rationale:
Natural products can provide structurally diverse molecules with
biologic activity that serve as starting points for lead optimization. A is
incorrect because many natural products have poor absorption, rapid
metabolism, or other pharmacokinetic limitations. B is incorrect
because activity of a natural product does not establish its precise
human mechanism. D is incorrect because natural origin does not
guarantee safety.
Question 3
A purified plant-derived compound demonstrates promising
antibacterial activity but has very poor water solubility. Which approach
best reflects a rational drug-discovery strategy?
A. Abandon the compound immediately
B. Increase the dose until the desired concentration is reached
C. Modify the chemical structure to improve physicochemical properties
while preserving activity
D. Replace all biological testing with computational modeling
Correct Answer:
C. Modify the chemical structure to improve physicochemical properties
while preserving activity
Rationale:
A promising lead may require optimization of solubility, stability,
absorption, potency, or selectivity. Structural modification can improve
