Deck 36: Drug Development

Question 1

Which of the following enzymes is associated with the inflammatory response?

A) phosphodiesterase 5
B) HMG-CoA reductase
C) $\beta$ -lactamase
D) cyclooxygenase 2
E) None of the answers is correct.

Answer 1

cyclooxygenase 2

Question 2

The most notable structural feature of penicillin is a four-membered ring referred to as a ______________ ring.

Answer 2

β-lactam

Question 3

What concentration of a drug gives 90% of the maximum response?

A) DC₉₀
B) EC₉₀
C) LC₉₀
D) MC₉₀
E) RC₉₀

Answer 3

B

Question 4

Penicillin inhibits the action of the ____________________ (type of enzyme)that catalyzes the formation of cross-links in bacterial cell walls.

Question 5

__________________ is an abundant protein that binds to and transports drugs everywhere the bloodstream flows.

Question 6

In which phase of drug development do healthy volunteers take the drug for initial safety studies?

A) phase I trials
B) phase II trials
C) phase III trials
D) pre-clinical trials
E) None of the answers is correct.

Question 7

The current cost of developing a new drug is ____________ .

Question 8

Who is credited with the discovery of penicillin?

A) Louis Pasteur
B) Alexander Fleming
C) Selman Waksman
D) Paul Ehrlich
E) Gerhard Domagk

Question 9

What term describes a molecule that binds to a target molecule?

A) substrate
B) effector
C) ligand
D) cosubstrate
E) None of the answers is correct.

Question 10

K_d corresponds to the concentration of ligand,at which ______________ (fraction?)of the receptors are bound to ligand.

Question 11

________________ is the science that deals with the discovery,chemistry,composition,identification,biological and physiological effects,uses,and manufacture of drugs.

Question 12

What set of "rules" gives a general indication of the bioavailability of a drug?

A) Lipovec
B) Lipper
C) Lippincott
D) Lipinski
E) Lipkowicz

Question 13

What compound is increased by the action of Sildenafil (Viagra)?

A) GTP
B) ATP
C) AMP
D) cAMP
E) cGMP

Question 14

What method,employed in combinatorial chemistry,begins by dividing the starting scaffold into a number of sets?

A) rational drug design
B) solid phase synthesis
C) split pool synthesis
D) high-throughput screening
E) None of the answers is correct.

Question 15

Which of the following is conjugated to drugs to aid excretion?

A) glucuronic acid
B) cholic acid
C) glutamic acid
D) ascorbic acid
E) None of the answers is correct.

Question 16

Thiopurine drugs,such as 6-thioguanine,are toxic to some individuals because they have a genetic variation of the enzyme _________________________.

Question 17

A drug's concentration at its target site is affected by its ADME,which is an acronym that stands for _________________________________.

Question 18

Which of the following class of drugs is a common treatment for hypertension?

A) beta blocker
B) statins
C) protease inhibitors
D) phosphodiesterase inhibitors
E) None of the answers is correct.

Question 19

Some bacteria are resistant to penicillin because they contain __________________ enzymes.

Question 20

Which of the following is NOT one of the factors that predicts the bioavailability of a drug?

A) The molecular weight is less than 500.
B) The number of hydrogen-bond donors is less than 5.
C) The number of hydrogen-bond acceptors is less than 10.
D) The partition coefficient is less than 5.
E) The structure contains at least two aromatic rings.

Question 21

Briefly describe the factors that will determine the concentration of a drug at the target site in the body.

Question 22

If you do a Google search for Lipinski's rules,you will observe that this predictor of bioavailability is also referred to as the "Rule of 5." Explain.

Question 23

Which of the following is a powerful animal model used for drug development?

A) fruit fly models with specific genes "knocked out"
B) bovine models with specific genes "knocked out"
C) E. coli models with specific plasmids added
D) mouse strains with specific genes "knocked out"
E) None of the answers is correct.

Question 24

Give a chemical equation for the general reaction that is catalyzed by cytochrome P450 in the metabolism of a drug.Show the functional group that is added to the molecule.

Question 25

)What type of bond is used to link a glucuronic acid group to a xenobiotic?

A) eEster
B) gGlycosidic
C) aAmide
D) pPhosphoester
E) tThioether

Question 26

Sketch the binding curve for the titration of a receptor R with a ligand L,and label the point on the plot that corresponds to the K_d for the RL complex.

Question 27

A compound that inhibits HMG-CoA reductase has potential use as a drug that

A) reduces inflammation and can be used to treat arthritis.
B) reduces stomach acid production and can be used to treat ulcers.
C) reduces blood cholesterol and can be used to treat atherosclerosis.
D) increases the concentration of cGMP and can be used to treat erectile dysfunction.
E) increases dopamine and can be used to treat schizophrenia.

Question 28

Which of the following is NOT commonly conjugated to a xenobiotic?

A) glucuronic acid
B) sulfate group
C) glutathione
D) salicylic acid
E) None of the answers is correct.

Question 29

Give three types of conjugation reactions that occur in the metabolism of xenobiotics.

Question 30

First attempts to develop cholesterol-lowering drugs targeted the later steps in cholesterol biosynthesis.Why did this strategy have to be abandoned?

A) These reactions were so efficient that they could not be blocked.
B) The accumulation of an insoluble substrate caused cataracts and other deleterious side effects.
C) All of the drugs that were developed actually enhanced cholesterol synthesis.
D) None of the drugs that were developed could survive the acid conditions in the stomach.
E) These drugs caused untreatable gall stones.

Question 31

Which of the following drugs were developed as a result of information obtained from a mouse model that had the gene that normally produces the α-subunit of the H⁺,K⁺ ATPase transport system "knocked out"?

A) Prilosec and Prevacid
B) Celebrex and Viox
C) Crixivan
D) Lipitor and Crestor
E) Viagra

Question 32

Which of the following properties affects the effective concentration of a drug at the target site?

A) the rate of absorption of the drug
B) the extent of distribution or compartmentalization of the drug
C) the efficiency of metabolism of the drug
D) the ease of excretion of the drug and/or its metabolites
E) All of the answers are correct.

Question 33

Drug candidateIC₅₀(nmol)Log (P)C_max (µM)BioavailabilityA0.44.67<0.1B0.013.70<0.1C0.33.690.7D0.62.9211Consider the information concerning a related class of potential drugs in the table above.Which one would be the best candidate for further testing?

A) A
B) B
C) C
D) D
E) None of the answers are suitable.

Question 34

Elevated doses of acetaminophen are toxic because an oxidized metabolite reacts with and depletes which of the following compounds that normally protects the liver and other vital organs?

A) glutathione
B) cGMP
C) plasma albumin
D) vyclooxygenase I
E) cytochrome P450

Question 35

Drug candidateIC₅₀(nmol)Log (P)C_max (µM)BioavailabilityA0.44.67<0.1B0.013.70<0.1C0.33.690.7D0.62.9211Consider the information concerning a related class of potential drugs in the table above.Which one is least soluble in water and most hydrophobic?

A) A
B) B
C) C
D) D
E) They are all equally soluble in water.

Question 36

Describe what factors will affect the apparent K_d of a drug under physiological conditions.

Question 37

What type of reaction is typically catalyzed by liver cytochrome P450?

A) reduction
B) hydration
C) hydroxylation
D) hydrolysis
E) esterification

Question 38

Successful drugs have been discovered by which of the following methods?

A) chance observation of a beneficial, though unplanned, physiological effect
B) screening natural products with interesting activities
C) combinatorial chemical synthesis of large collections of chemically related compounds for screening
D) if the structure of the target is known, computer-aided design of compounds that might bind to the target
E) All of the answers are correct.

Question 39

Briefly explain why a drug candidate that has a partition coefficient (log P)greater than 5 is not a good candidate for oral bioavailability.

Question 40

Which of the following is correct concerning the dissociation constant,K_d,of a drug X?

A) A larger K_d implies tighter target to drug binding.
B) The K_d corresponds to the concentration of drug that binds to 90% of the target.
C) The K_d can be determined from the simple saturation curve of a binding reaction.
D) The apparent K_d increases as the K_M of the true substrate increases.
E) None of the answers is correct.

Question 41

Give an example of how a drug was discovered by a chance observation.

Question 42

How is genomic information used to develop new drugs?

Question 43

Give the reaction by which a glucuronate group (pH 7)is conjugated to a metabolite,and briefly explain the advantage of this metabolic process.

Question 44

Why do some drug treatments become ineffective over time?

Question 45

Cyclooxygenase 2 is expressed primarily as part of the inflammatory response,whereas cyclooxygenase 1 is expressed more generally.Celecoxib (Celebrex)was designed to target COX2 and is used to reduce inflammation due to arthritis.What structural feature of Celecoxib (Celebrex)makes this drug more selective for COX2 instead of COX1?

Question 46

Thiopurines such as 6-thioguanine are used to treat immune disorders and leukemia.Some individuals who are treated show signs of toxicity at doses well tolerated by most patients.Explain the reason for this toxicity.

Question 47

Describe how certain bacteria can development resistance to penicillin.

Question 48

Briefly describe split-pool synthesis