NUSCTX 110 Midterm 1 UPDATED
ACTUAL Exam Questions and CORRECT
Answers
On-Target Toxicity - CORRECT ANSWER - Toxic effect due to the drug interacting with
the intended therapeutic target
Off-Target Toxicity - CORRECT ANSWER - Toxic effect due to the drug interacting with
an unintended biological target or unintended tissue
Idiosyncratic drug reactions - CORRECT ANSWER - drug reactions that occur rarely and
unpredictably
Idiopathic drug reactions - CORRECT ANSWER - when the cause of toxicity in a drug is
unknown
Rosiglitazone - CORRECT ANSWER - •It was prescribed as an insulin sensitizer for
diabetics by binding to PPAR-gamma receptors in adipocytes•First released in 1999, annual sales
peaked at 2.5 billion in 2006 and use has declined dramatically after drug was found to increase
risk of heart attacks.•Adverse effects subject to over 13,000 lawsuits and has been estimated to
have caused 83,000 heart attacks in the US•Rosiglitazone causes on-target edema which can put
people at risk for congestive heart failure—occurs through reduced renal excretion of sodium
and increase in sodium and water retention
Non-Steroidal Anti-Inflammatory Drugs - CORRECT ANSWER - Non-Steroidal Anti-
Inflammatory Drugs—Aspirin, Ibuprofen, Diclofenac, Naproxen, acetaminophen•Used for pain
relief, inflammation, fever reduction and swelling, arthritis, headache•Acetylsalicilic acid (active
ingredient of aspirin) is produced by plants including willow bark and spiraea
Rofecoxib (Vioxx) - CORRECT ANSWER - •COX2-selective inhibitor with very little
gastrointestinal side-effects•Prescribed to over 20 million people as a pain reliever for
arthritis•was found to be responsible for increased risk of heart attack and stroke•Recalled in
2004; Financial damage: nearly $6 billion in litigation•Largest drug recall in history•Merck and
,FDA criticized for ignoring evidence of dangers of Vioxx before its eventual recall•140,000
people could have suffered serious coronary heart disease from taking the drug in just the
U.S.•Studies have shown that COX2 is responsible for synthesis of prostacyclins in the
vasculature which are cardioprotective•COX2-selective inhibition reduces the cardioprotective
prostacyclin and causes cardiac events
Diphenhydramine - CORRECT ANSWER - •Diphenhydramine also crosses the blood
brain barrier where H1 histamine receptor antagonism causes sleepiness.•Modern antihistamines,
such as claritin, do not cross the blood brain barrier
Toxicology - CORRECT ANSWER - Toxicology is the study of adverse effects of
chemicals on living systems, including:•Mechanisms of action and exposure to chemicals as a
cause of acute and chronic illness.•Recognition, identification, quantification of hazards from
occupational exposure to chemicals. •Discovery of new drugs and pesticides and characterizing
their safety, ADME, toxicology.•Development of standards and regulations to protect humans
and the environment from adverse effects of chemicals.
Terfenadine - CORRECT ANSWER - a non-sedating antihistamineformerly used for
treatment of allergic conditions by Sanofi Aventis•Was used by over 100 million patients by
1990 and made over $440 million•Replaced by fexofenadine in the 1990s due to risk of cardiac
arrhythmia
Thalidomide - CORRECT ANSWER - •Thalidomide was an anti-nausea and sedative drug
that was introduced in the late 1950s to be used to help with morning sickness•1950s to 1960s:
more than 10,000 children in 46 countries were born with deformities such as phocomelia
involving shortened limbs R-thalidomide stimulates the GABA receptor to cause sedative effects.
•S-thalidomide binds to a protein and inactivates a protein called cereblon (CRBN), an E3
ubiquitin ligase that, when bound to thalidomide, recruits neo-substrates to ubiquitinate and
proteasomally degrade them—including a recently identified transcription factor called SALL4
which is involved in limb outgrowth and development
1.How do most small-molecule drugs that are in the clinic work to exert their therapeutic action?
- CORRECT ANSWER - a.Most small-molecule drugs bind to a pocket in a protein and
inhibits or activates that protein, but that protein is not degraded
b.Most small-molecule drugs bind to a gene and turn on or turn off that gene
c.Most small-molecule drugs edit your genome to repair inborn errors
, d.Most small-molecule drugs bind to a pocket in a protein and gets degraded
2.What is involved in a typical drug discovery campaign to get to clinical trials? - CORRECT
ANSWER - a.Target selection, screening small-molecule libraries to discover hits, take the
hit compound and file an IND to the FDA and enter Phase I clinical trials
b.Target selection, screening small-molecule libraries to discover hits, hit to lead medicinal
chemistry optimization to improve potency, selectivity, and pharmacokinetic/pharmacodynamic
parameters to get to a developmental candidate (DC), testing safety, metabolism, efficacy,
optimizing process chemistry and formulation, filing an Investigational New Drug Application
(IND) to Food and Drug Administration (FDA), and entering Phase I clinical trials
c.Formulating a nutrient supplement cocktail, announce its efficacy on social media and news
outlets, sell to patients online
d.Hearing rumors about the efficacy of a drug, touting to the media and press that it cures a
potentially lethal disease, and strong-arming the FDA to cross-indicate the drug for the lethal
disease by passing emergency approval of the drug before clinical trials are finished
3.What is the therapeutic mechanism of action of the non-steroidal anti-inflammatory drug
ibuprofen? What is the toxicity associated with ibuprofen and what is the toxicological
mechanism? Is this toxicity an on or off-target effect? - CORRECT ANSWER -
You find out that the drug that you are developing that acts through antagonizing the histamine
receptor, also inhibits the cardiac potassium channel (hERG). What type of toxicity might you
expect from your drug? Is this an on or off-target effect? - CORRECT ANSWER -
What was the therapeutic mechanism of action of the morning sickness drug thalidomide? What
was the toxicity associated with thalidomide and what was the toxicological mechanism? Was
this an on or off-target toxicity? - CORRECT ANSWER -
How does thalidomide work as an anti-cancer drug to treat multiple myeloma? - CORRECT
ANSWER -
How are thalidomide and other E3 ubiquitin ligase recruiters now utilized to target specific
proteins for ubiquitin-mediated proteasomal degradation in the pharmaceutical industry -
CORRECT ANSWER -
ACTUAL Exam Questions and CORRECT
Answers
On-Target Toxicity - CORRECT ANSWER - Toxic effect due to the drug interacting with
the intended therapeutic target
Off-Target Toxicity - CORRECT ANSWER - Toxic effect due to the drug interacting with
an unintended biological target or unintended tissue
Idiosyncratic drug reactions - CORRECT ANSWER - drug reactions that occur rarely and
unpredictably
Idiopathic drug reactions - CORRECT ANSWER - when the cause of toxicity in a drug is
unknown
Rosiglitazone - CORRECT ANSWER - •It was prescribed as an insulin sensitizer for
diabetics by binding to PPAR-gamma receptors in adipocytes•First released in 1999, annual sales
peaked at 2.5 billion in 2006 and use has declined dramatically after drug was found to increase
risk of heart attacks.•Adverse effects subject to over 13,000 lawsuits and has been estimated to
have caused 83,000 heart attacks in the US•Rosiglitazone causes on-target edema which can put
people at risk for congestive heart failure—occurs through reduced renal excretion of sodium
and increase in sodium and water retention
Non-Steroidal Anti-Inflammatory Drugs - CORRECT ANSWER - Non-Steroidal Anti-
Inflammatory Drugs—Aspirin, Ibuprofen, Diclofenac, Naproxen, acetaminophen•Used for pain
relief, inflammation, fever reduction and swelling, arthritis, headache•Acetylsalicilic acid (active
ingredient of aspirin) is produced by plants including willow bark and spiraea
Rofecoxib (Vioxx) - CORRECT ANSWER - •COX2-selective inhibitor with very little
gastrointestinal side-effects•Prescribed to over 20 million people as a pain reliever for
arthritis•was found to be responsible for increased risk of heart attack and stroke•Recalled in
2004; Financial damage: nearly $6 billion in litigation•Largest drug recall in history•Merck and
,FDA criticized for ignoring evidence of dangers of Vioxx before its eventual recall•140,000
people could have suffered serious coronary heart disease from taking the drug in just the
U.S.•Studies have shown that COX2 is responsible for synthesis of prostacyclins in the
vasculature which are cardioprotective•COX2-selective inhibition reduces the cardioprotective
prostacyclin and causes cardiac events
Diphenhydramine - CORRECT ANSWER - •Diphenhydramine also crosses the blood
brain barrier where H1 histamine receptor antagonism causes sleepiness.•Modern antihistamines,
such as claritin, do not cross the blood brain barrier
Toxicology - CORRECT ANSWER - Toxicology is the study of adverse effects of
chemicals on living systems, including:•Mechanisms of action and exposure to chemicals as a
cause of acute and chronic illness.•Recognition, identification, quantification of hazards from
occupational exposure to chemicals. •Discovery of new drugs and pesticides and characterizing
their safety, ADME, toxicology.•Development of standards and regulations to protect humans
and the environment from adverse effects of chemicals.
Terfenadine - CORRECT ANSWER - a non-sedating antihistamineformerly used for
treatment of allergic conditions by Sanofi Aventis•Was used by over 100 million patients by
1990 and made over $440 million•Replaced by fexofenadine in the 1990s due to risk of cardiac
arrhythmia
Thalidomide - CORRECT ANSWER - •Thalidomide was an anti-nausea and sedative drug
that was introduced in the late 1950s to be used to help with morning sickness•1950s to 1960s:
more than 10,000 children in 46 countries were born with deformities such as phocomelia
involving shortened limbs R-thalidomide stimulates the GABA receptor to cause sedative effects.
•S-thalidomide binds to a protein and inactivates a protein called cereblon (CRBN), an E3
ubiquitin ligase that, when bound to thalidomide, recruits neo-substrates to ubiquitinate and
proteasomally degrade them—including a recently identified transcription factor called SALL4
which is involved in limb outgrowth and development
1.How do most small-molecule drugs that are in the clinic work to exert their therapeutic action?
- CORRECT ANSWER - a.Most small-molecule drugs bind to a pocket in a protein and
inhibits or activates that protein, but that protein is not degraded
b.Most small-molecule drugs bind to a gene and turn on or turn off that gene
c.Most small-molecule drugs edit your genome to repair inborn errors
, d.Most small-molecule drugs bind to a pocket in a protein and gets degraded
2.What is involved in a typical drug discovery campaign to get to clinical trials? - CORRECT
ANSWER - a.Target selection, screening small-molecule libraries to discover hits, take the
hit compound and file an IND to the FDA and enter Phase I clinical trials
b.Target selection, screening small-molecule libraries to discover hits, hit to lead medicinal
chemistry optimization to improve potency, selectivity, and pharmacokinetic/pharmacodynamic
parameters to get to a developmental candidate (DC), testing safety, metabolism, efficacy,
optimizing process chemistry and formulation, filing an Investigational New Drug Application
(IND) to Food and Drug Administration (FDA), and entering Phase I clinical trials
c.Formulating a nutrient supplement cocktail, announce its efficacy on social media and news
outlets, sell to patients online
d.Hearing rumors about the efficacy of a drug, touting to the media and press that it cures a
potentially lethal disease, and strong-arming the FDA to cross-indicate the drug for the lethal
disease by passing emergency approval of the drug before clinical trials are finished
3.What is the therapeutic mechanism of action of the non-steroidal anti-inflammatory drug
ibuprofen? What is the toxicity associated with ibuprofen and what is the toxicological
mechanism? Is this toxicity an on or off-target effect? - CORRECT ANSWER -
You find out that the drug that you are developing that acts through antagonizing the histamine
receptor, also inhibits the cardiac potassium channel (hERG). What type of toxicity might you
expect from your drug? Is this an on or off-target effect? - CORRECT ANSWER -
What was the therapeutic mechanism of action of the morning sickness drug thalidomide? What
was the toxicity associated with thalidomide and what was the toxicological mechanism? Was
this an on or off-target toxicity? - CORRECT ANSWER -
How does thalidomide work as an anti-cancer drug to treat multiple myeloma? - CORRECT
ANSWER -
How are thalidomide and other E3 ubiquitin ligase recruiters now utilized to target specific
proteins for ubiquitin-mediated proteasomal degradation in the pharmaceutical industry -
CORRECT ANSWER -
