NUSCTX 110 Toxicology Midterm 1 Exam Questions and Answers With Verified
Solutions 2025
On-Target Toxicity - ✔✔Toxic effect due to the drug interacting with the intended therapeutic target
Off-Target Toxicity - ✔✔Toxic effect due to the drug interacting with an unintended biological target or
unintended tissue
Idiosyncratic drug reactions - ✔✔drug reactions that occur rarely and unpredictably
Idiopathic drug reactions - ✔✔when the cause of toxicity in a drug is unknown
Rosiglitazone - ✔✔•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 - ✔✔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) - ✔✔•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 - ✔✔•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 - ✔✔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 - ✔✔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 - ✔✔•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? -
✔✔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? - ✔✔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
Solutions 2025
On-Target Toxicity - ✔✔Toxic effect due to the drug interacting with the intended therapeutic target
Off-Target Toxicity - ✔✔Toxic effect due to the drug interacting with an unintended biological target or
unintended tissue
Idiosyncratic drug reactions - ✔✔drug reactions that occur rarely and unpredictably
Idiopathic drug reactions - ✔✔when the cause of toxicity in a drug is unknown
Rosiglitazone - ✔✔•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 - ✔✔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) - ✔✔•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 - ✔✔•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 - ✔✔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 - ✔✔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 - ✔✔•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? -
✔✔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? - ✔✔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
