Goodman and Gilman's The
Pharmacological Basis of Therapeutics
14th Edition
• Author(s)Laurence Brunton; Bjorn
Knollmann
FAST-REVISION / STUDY-GUIDE–STYLE
MCQ
Test Bank
1. A novel small molecule is optimized to bind a kinase active
site by iteratively altering substituents to improve potency
while reducing off-target binding. This process best
describes:
A. High-throughput screening
B. Lead optimization (structure–activity relationship
studies)
, C. Pharmacovigilance
D. Phase I clinical testing
Correct: B
Rationale: Lead optimization uses SAR (structure–activity
relationships) to modify chemical groups to improve
potency/selectivity and reduce off-target effects.
Citation: Goodman & Gilman, 14th ed., Chapter “Drug
Discovery: From Medicinal Plants to Computer-Aided Drug
Design.”
2. Which principle is most closely associated with Lipinski’s
“Rule of Five” in early drug design?
A. Predicting toxicity in humans
B. Predicting oral bioavailability based on physicochemical
properties
C. Selecting compounds for IV administration only
D. Identifying drug–drug interactions with CYP enzymes
Correct: B
Rationale: Lipinski’s rules (molecular weight, H-bond
donors/acceptors, lipophilicity) estimate oral absorption and
permeability, guiding selection for oral drugs.
Citation: Goodman & Gilman, 14th ed., Chapter “Drug
Discovery: From Medicinal Plants to Computer-Aided Drug
Design.”
, 3. A drug candidate shows excellent potency in vitro but fails
in vivo due to rapid hepatic metabolism. The most relevant
early development strategy to address this is:
A. Increase the in vitro assay concentration
B. Design a prodrug or alter structure to reduce first-pass
metabolism
C. Proceed directly to Phase II trials
D. Abandon the target
Correct: B
Rationale: Structural modification or prodrug approaches can
improve metabolic stability and oral bioavailability by reducing
rapid hepatic clearance.
Citation: Goodman & Gilman, 14th ed., Chapter “Drug
Discovery: From Medicinal Plants to Computer-Aided Drug
Design.”
4. In high-throughput screening (HTS), frequent false
positives arise from compounds that interfere non-
specifically in assays (e.g., aggregate formation). These
problematic molecules are called:
A. Biologics
B. Orphan drugs
C. PAINS (pan-assay interference compounds)
D. ADME compounds
Correct: C
Rationale: PAINS are chemical motifs that give artifacts across
,many assay types and must be filtered out during hit triage.
Citation: Goodman & Gilman, 14th ed., Chapter “Drug
Discovery: From Medicinal Plants to Computer-Aided Drug
Design.”
5. Which strategy uses three-dimensional protein structure to
design or refine ligands that fit a specific binding pocket?
A. Combinatorial chemistry
B. Phenotypic screening
C. Structure-based drug design (molecular docking)
D. Mass spectrometry profiling
Correct: C
Rationale: Structure-based design (including docking) uses the
target’s 3D structure to model ligand–target interactions and
guide chemical design.
Citation: Goodman & Gilman, 14th ed., Chapter “Drug
Discovery: From Medicinal Plants to Computer-Aided Drug
Design.”
6. A new compound is a substrate for P-glycoprotein (P-gp).
Clinically, this is most likely to affect:
A. Renal glomerular filtration rate
B. Oral absorption and brain penetration (limited CNS
entry)
, C. Plasma protein binding only
D. Rate of phase II conjugation
Correct: B
Rationale: P-gp efflux decreases intestinal absorption and limits
CNS penetration by pumping substrates out of enterocytes and
across the blood–brain barrier.
Citation: Goodman & Gilman, 14th ed., Chapter “Drug
Discovery: From Medicinal Plants to Computer-Aided Drug
Design.”
7. In silico ADMET prediction is used in early discovery
primarily to:
A. Replace all animal testing
B. Prioritize compounds with favorable absorption,
distribution, metabolism, excretion, and toxicity profiles
C. Guarantee absence of human toxicity
D. Design Phase III clinical protocols
Correct: B
Rationale: Computational ADMET screens help triage
compounds likely to fail for PK or toxicity, improving selection
before costly studies.
Citation: Goodman & Gilman, 14th ed., Chapter “Drug
Discovery: From Medicinal Plants to Computer-Aided Drug
Design.”
, 8. When a drug candidate inhibits a major CYP isoform in
vitro, the key nursing implication once the drug is
marketed will most likely be:
A. Avoiding all concomitant drugs
B. Monitoring for clinically significant drug–drug
interactions and educating patients about co-medications
metabolized by that CYP
C. No special action; CYP inhibition is irrelevant clinically
D. Advising patients to stop all OTC medications
Correct: B
Rationale: CYP inhibition can raise concentrations of co-
medications; nurses should watch for interaction signs and
counsel about concomitant drug risks.
Citation: Goodman & Gilman, 14th ed., Chapter “Drug
Discovery: From Medicinal Plants to Computer-Aided Drug
Design.”
9. Ethnopharmacology (examining medicinal plants used
traditionally) is important in drug discovery because:
A. It always produces safe, approved drugs without further
testing
B. It provides bioactive lead compounds and structural
scaffolds for synthetic optimization
C. It eliminates the need for preclinical toxicology
D. It guarantees oral bioavailability
,Correct: B
Rationale: Traditional use can point to biologically active
compounds that serve as leads or scaffolds for further
medicinal chemistry and optimization.
Citation: Goodman & Gilman, 14th ed., Chapter “Drug
Discovery: From Medicinal Plants to Computer-Aided Drug
Design.”
10. A drug’s therapeutic index (TI) is defined as the ratio
of:
A. Effective concentration to elimination half-life
B. Toxic dose (or concentration) to effective dose (or
concentration) — a measure of safety margin
C. Absorption rate to distribution volume
D. Bioavailability to clearance
Correct: B
Rationale: TI = (toxic dose)/(effective dose); a larger TI indicates
a wider safety margin important for clinical monitoring and
dosing decisions.
Citation: Goodman & Gilman, 14th ed., Chapter “Drug
Discovery: From Medicinal Plants to Computer-Aided Drug
Design.”
11. Which preclinical test is most directly aimed at
detecting a compound’s potential to cause genetic
, mutations?
A. Ames test (bacterial reverse mutation assay)
B. hERG channel assay
C. Maximum tolerated dose (MTD) study in rodents
D. Reproductive toxicity study
Correct: A
Rationale: The Ames test screens for mutagenicity using
bacterial strains; it is a standard early genetoxicity assessment.
Citation: Goodman & Gilman, 14th ed., Chapter “Drug
Discovery: From Medicinal Plants to Computer-Aided Drug
Design.”
12. A candidate drug prolongs the QT interval in vitro by
blocking hERG potassium channels. The most appropriate
action during development is:
A. Increase the clinical starting dose
B. Modify chemical structure to reduce hERG affinity and
re-test cardiac liability
C. Skip clinical cardiac monitoring
D. Ignore, because in vitro findings do not predict in vivo
risk
Correct: B
Rationale: hERG blockade risks torsades de pointes; structural
modification to lower hERG activity is a standard mitigation
before clinical testing.
Citation: Goodman & Gilman, 14th ed., Chapter “Drug
,Discovery: From Medicinal Plants to Computer-Aided Drug
Design.”
13. Drug repurposing/redirecting (finding new
therapeutic uses for existing drugs) is attractive because it:
A. Eliminates all regulatory requirements
B. Often shortens development time and reduces risk
because safety data already exist
C. Guarantees efficacy in new indications
D. Is only applicable to biologics
Correct: B
Rationale: Repurposing leverages prior safety/tox data,
potentially speeding development and lowering attrition
compared with de novo discovery.
Citation: Goodman & Gilman, 14th ed., Chapter “Drug
Discovery: From Medicinal Plants to Computer-Aided Drug
Design.”
14. Combinatorial chemistry primarily contributes to drug
discovery by:
A. Testing drug effects in humans faster
B. Enabling rapid synthesis of large libraries of related
compounds for screening
C. Replacing medicinal chemistry optimization steps
, entirely
D. Guaranteeing target selectivity
Correct: B
Rationale: Combinatorial techniques generate many structural
analogs rapidly, expanding chemical diversity for screening and
lead identification.
Citation: Goodman & Gilman, 14th ed., Chapter “Drug
Discovery: From Medicinal Plants to Computer-Aided Drug
Design.”
15. A lead candidate with low aqueous solubility
demonstrates poor oral exposure. Which formulation or
design strategy is commonly used to address this?
A. Increase molecular weight
B. Use salt forms, particle size reduction, or lipid-based
formulations to enhance dissolution and bioavailability
C. Decrease lipophilicity to zero
D. Eliminate oral route and mandate topical use only
Correct: B
Rationale: Pharmaceutical formulation techniques (salt
formation, micronization, lipid vehicles) improve solubility and
hence oral absorption.
Citation: Goodman & Gilman, 14th ed., Chapter “Drug
Discovery: From Medicinal Plants to Computer-Aided Drug
Design.”
Pharmacological Basis of Therapeutics
14th Edition
• Author(s)Laurence Brunton; Bjorn
Knollmann
FAST-REVISION / STUDY-GUIDE–STYLE
MCQ
Test Bank
1. A novel small molecule is optimized to bind a kinase active
site by iteratively altering substituents to improve potency
while reducing off-target binding. This process best
describes:
A. High-throughput screening
B. Lead optimization (structure–activity relationship
studies)
, C. Pharmacovigilance
D. Phase I clinical testing
Correct: B
Rationale: Lead optimization uses SAR (structure–activity
relationships) to modify chemical groups to improve
potency/selectivity and reduce off-target effects.
Citation: Goodman & Gilman, 14th ed., Chapter “Drug
Discovery: From Medicinal Plants to Computer-Aided Drug
Design.”
2. Which principle is most closely associated with Lipinski’s
“Rule of Five” in early drug design?
A. Predicting toxicity in humans
B. Predicting oral bioavailability based on physicochemical
properties
C. Selecting compounds for IV administration only
D. Identifying drug–drug interactions with CYP enzymes
Correct: B
Rationale: Lipinski’s rules (molecular weight, H-bond
donors/acceptors, lipophilicity) estimate oral absorption and
permeability, guiding selection for oral drugs.
Citation: Goodman & Gilman, 14th ed., Chapter “Drug
Discovery: From Medicinal Plants to Computer-Aided Drug
Design.”
, 3. A drug candidate shows excellent potency in vitro but fails
in vivo due to rapid hepatic metabolism. The most relevant
early development strategy to address this is:
A. Increase the in vitro assay concentration
B. Design a prodrug or alter structure to reduce first-pass
metabolism
C. Proceed directly to Phase II trials
D. Abandon the target
Correct: B
Rationale: Structural modification or prodrug approaches can
improve metabolic stability and oral bioavailability by reducing
rapid hepatic clearance.
Citation: Goodman & Gilman, 14th ed., Chapter “Drug
Discovery: From Medicinal Plants to Computer-Aided Drug
Design.”
4. In high-throughput screening (HTS), frequent false
positives arise from compounds that interfere non-
specifically in assays (e.g., aggregate formation). These
problematic molecules are called:
A. Biologics
B. Orphan drugs
C. PAINS (pan-assay interference compounds)
D. ADME compounds
Correct: C
Rationale: PAINS are chemical motifs that give artifacts across
,many assay types and must be filtered out during hit triage.
Citation: Goodman & Gilman, 14th ed., Chapter “Drug
Discovery: From Medicinal Plants to Computer-Aided Drug
Design.”
5. Which strategy uses three-dimensional protein structure to
design or refine ligands that fit a specific binding pocket?
A. Combinatorial chemistry
B. Phenotypic screening
C. Structure-based drug design (molecular docking)
D. Mass spectrometry profiling
Correct: C
Rationale: Structure-based design (including docking) uses the
target’s 3D structure to model ligand–target interactions and
guide chemical design.
Citation: Goodman & Gilman, 14th ed., Chapter “Drug
Discovery: From Medicinal Plants to Computer-Aided Drug
Design.”
6. A new compound is a substrate for P-glycoprotein (P-gp).
Clinically, this is most likely to affect:
A. Renal glomerular filtration rate
B. Oral absorption and brain penetration (limited CNS
entry)
, C. Plasma protein binding only
D. Rate of phase II conjugation
Correct: B
Rationale: P-gp efflux decreases intestinal absorption and limits
CNS penetration by pumping substrates out of enterocytes and
across the blood–brain barrier.
Citation: Goodman & Gilman, 14th ed., Chapter “Drug
Discovery: From Medicinal Plants to Computer-Aided Drug
Design.”
7. In silico ADMET prediction is used in early discovery
primarily to:
A. Replace all animal testing
B. Prioritize compounds with favorable absorption,
distribution, metabolism, excretion, and toxicity profiles
C. Guarantee absence of human toxicity
D. Design Phase III clinical protocols
Correct: B
Rationale: Computational ADMET screens help triage
compounds likely to fail for PK or toxicity, improving selection
before costly studies.
Citation: Goodman & Gilman, 14th ed., Chapter “Drug
Discovery: From Medicinal Plants to Computer-Aided Drug
Design.”
, 8. When a drug candidate inhibits a major CYP isoform in
vitro, the key nursing implication once the drug is
marketed will most likely be:
A. Avoiding all concomitant drugs
B. Monitoring for clinically significant drug–drug
interactions and educating patients about co-medications
metabolized by that CYP
C. No special action; CYP inhibition is irrelevant clinically
D. Advising patients to stop all OTC medications
Correct: B
Rationale: CYP inhibition can raise concentrations of co-
medications; nurses should watch for interaction signs and
counsel about concomitant drug risks.
Citation: Goodman & Gilman, 14th ed., Chapter “Drug
Discovery: From Medicinal Plants to Computer-Aided Drug
Design.”
9. Ethnopharmacology (examining medicinal plants used
traditionally) is important in drug discovery because:
A. It always produces safe, approved drugs without further
testing
B. It provides bioactive lead compounds and structural
scaffolds for synthetic optimization
C. It eliminates the need for preclinical toxicology
D. It guarantees oral bioavailability
,Correct: B
Rationale: Traditional use can point to biologically active
compounds that serve as leads or scaffolds for further
medicinal chemistry and optimization.
Citation: Goodman & Gilman, 14th ed., Chapter “Drug
Discovery: From Medicinal Plants to Computer-Aided Drug
Design.”
10. A drug’s therapeutic index (TI) is defined as the ratio
of:
A. Effective concentration to elimination half-life
B. Toxic dose (or concentration) to effective dose (or
concentration) — a measure of safety margin
C. Absorption rate to distribution volume
D. Bioavailability to clearance
Correct: B
Rationale: TI = (toxic dose)/(effective dose); a larger TI indicates
a wider safety margin important for clinical monitoring and
dosing decisions.
Citation: Goodman & Gilman, 14th ed., Chapter “Drug
Discovery: From Medicinal Plants to Computer-Aided Drug
Design.”
11. Which preclinical test is most directly aimed at
detecting a compound’s potential to cause genetic
, mutations?
A. Ames test (bacterial reverse mutation assay)
B. hERG channel assay
C. Maximum tolerated dose (MTD) study in rodents
D. Reproductive toxicity study
Correct: A
Rationale: The Ames test screens for mutagenicity using
bacterial strains; it is a standard early genetoxicity assessment.
Citation: Goodman & Gilman, 14th ed., Chapter “Drug
Discovery: From Medicinal Plants to Computer-Aided Drug
Design.”
12. A candidate drug prolongs the QT interval in vitro by
blocking hERG potassium channels. The most appropriate
action during development is:
A. Increase the clinical starting dose
B. Modify chemical structure to reduce hERG affinity and
re-test cardiac liability
C. Skip clinical cardiac monitoring
D. Ignore, because in vitro findings do not predict in vivo
risk
Correct: B
Rationale: hERG blockade risks torsades de pointes; structural
modification to lower hERG activity is a standard mitigation
before clinical testing.
Citation: Goodman & Gilman, 14th ed., Chapter “Drug
,Discovery: From Medicinal Plants to Computer-Aided Drug
Design.”
13. Drug repurposing/redirecting (finding new
therapeutic uses for existing drugs) is attractive because it:
A. Eliminates all regulatory requirements
B. Often shortens development time and reduces risk
because safety data already exist
C. Guarantees efficacy in new indications
D. Is only applicable to biologics
Correct: B
Rationale: Repurposing leverages prior safety/tox data,
potentially speeding development and lowering attrition
compared with de novo discovery.
Citation: Goodman & Gilman, 14th ed., Chapter “Drug
Discovery: From Medicinal Plants to Computer-Aided Drug
Design.”
14. Combinatorial chemistry primarily contributes to drug
discovery by:
A. Testing drug effects in humans faster
B. Enabling rapid synthesis of large libraries of related
compounds for screening
C. Replacing medicinal chemistry optimization steps
, entirely
D. Guaranteeing target selectivity
Correct: B
Rationale: Combinatorial techniques generate many structural
analogs rapidly, expanding chemical diversity for screening and
lead identification.
Citation: Goodman & Gilman, 14th ed., Chapter “Drug
Discovery: From Medicinal Plants to Computer-Aided Drug
Design.”
15. A lead candidate with low aqueous solubility
demonstrates poor oral exposure. Which formulation or
design strategy is commonly used to address this?
A. Increase molecular weight
B. Use salt forms, particle size reduction, or lipid-based
formulations to enhance dissolution and bioavailability
C. Decrease lipophilicity to zero
D. Eliminate oral route and mandate topical use only
Correct: B
Rationale: Pharmaceutical formulation techniques (salt
formation, micronization, lipid vehicles) improve solubility and
hence oral absorption.
Citation: Goodman & Gilman, 14th ed., Chapter “Drug
Discovery: From Medicinal Plants to Computer-Aided Drug
Design.”
