Deck 36: Drug Development

Question 1

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

Answer 1

Serum albumin or Plasma albumin

Question 2

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.

Answer 2

A

Question 3

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 3

cyclooxygenase 2

Question 4

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 5

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 6

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

Question 7

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

Question 8

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 9

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

Question 10

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 11

The current cost of developing a new drug is ____________ .

Question 12

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

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

Question 13

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

Question 14

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

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

Question 15

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

Question 16

Who is credited with the discovery of penicillin?

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

Question 17

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 18

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 19

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

Question 20

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

Question 21

Describe how certain bacteria can development resistance to penicillin.

Question 22

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 23

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 24

) 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 25

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 26

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 27

Briefly describe split-pool synthesis

Question 28

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 29

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 30

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 31

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 32

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 33

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

Question 34

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 35

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 36

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

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

Question 37

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

Question 38

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 39

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 40

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 41

Why do some drug treatments become ineffective over time?

Question 42

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 43

How is genomic information used to develop new drugs?

Question 44

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?