Question 1

Describe how certain bacteria can development resistance to penicillin.

Accepted Answer

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Question 2

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

Accepted Answer

Acetaminophen at elevated doses produces a toxic metabolite that depletes glutathione, a critical antioxidant that protects cells, particularly in the liver, from damage.

Question 3

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

Accepted Answer

The answer of Briefly explain why a drug candidate that...

Question 4

) 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

Accepted Answer

Glycosidic bonds are used to link a glucuronic acid group to a xenobiotic in the process of glucuronidation, a common pathway for the metabolism of various substances in the body.

Question 5

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.

Accepted Answer

Mouse strains with specific genes "knocked out" are a powerful animal model used for drug development because they allow researchers to study the effects of removing specific genes, helping to understand gene function and the potential impact of drugs on these genetic pathways.

Question 6

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.

Accepted Answer

The dissociation constant, $K_d$, is determined from the saturation curve of a binding reaction, reflecting the concentration at which half of the available binding sites are occupied by the drug. This makes option C correct. Options A, B, and D are incorrect as a larger $K_d$ indicates weaker binding, $K_d$ corresponds to the concentration at which 50% (not 90%) of the target is bound, and the apparent $K_d$ is not directly influenced by the $K_m$ of a substrate in the context provided.

Question 7

Briefly describe split-pool synthesis

Accepted Answer

The answer of Briefly describe split-pool synthesis...

Question 8

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.

Accepted Answer

The answer of Sketch the binding curve for the titration...

Question 9

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

Accepted Answer

Prilosec (omeprazole) and Prevacid (lansoprazole) are proton pump inhibitors (PPIs) that were developed to inhibit the H+/K+ ATPase in the gastric parietal cells, reducing stomach acid secretion. This mechanism is closely related to the information obtained from mouse models with a specific gene knockout affecting an ATPase transport system, which provided insights into the regulation of acid secretion and contributed to the development of these drugs.

Question 10

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.

Accepted Answer

All the methods listed (A through D) have been successfully used in drug discovery. Chance observations have led to the discovery of some drugs, natural products have historically been a rich source of new drugs, combinatorial chemistry has expanded the possibilities for synthetic compounds, and computer-aided design has become increasingly important as our understanding of molecular targets improves.

Question 11

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.

Accepted Answer

All of the listed properties affect the effective concentration of a drug at the target site. The rate of absorption influences how quickly a drug enters systemic circulation, the extent of distribution determines how widely and where within the body a drug is dispersed, the efficiency of metabolism can alter a drug's activity and duration of effect, and the ease of excretion impacts how long a drug and its metabolites remain in the body.

Question 12

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.

Accepted Answer

The answer of Give a chemical equation for the general...

Question 13

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

Accepted Answer

The answer of Describe what factors will affect the apparent...

Question 14

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.

Accepted Answer

The strategy had to be abandoned because blocking the later steps in cholesterol biosynthesis led to the accumulation of an insoluble substrate, which caused cataracts and other deleterious side effects.

Question 15

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.

Accepted Answer

The answer of If you do a Google search for...

Question 16

What type of reaction is typically catalyzed by liver cytochrome P450?
A) reduction
B) hydration
C) hydroxylation
D) hydrolysis
E) esterification

Accepted Answer

Cytochrome P450 enzymes in the liver primarily catalyze hydroxylation reactions, which involve the addition of a hydroxyl group (-OH) to substrates, making them more water-soluble and easier to excrete.

Question 17

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

Accepted Answer

The answer of Briefly describe the factors that will determine...

Question 18

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.

Accepted Answer

HMG-CoA reductase is an enzyme involved in the biosynthesis of cholesterol. Inhibiting this enzyme reduces the production of cholesterol, which can help in treating conditions like atherosclerosis that are associated with high cholesterol levels.

Question 19

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

Accepted Answer

The answer of Give the reaction by which a glucuronate...

Question 20

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.

Accepted Answer

Salicylic acid is itself a xenobiotic and not a molecule commonly used for conjugation to other xenobiotics. Glucuronic acid, sulfate groups, and glutathione are commonly involved in the conjugation processes to increase the solubility of xenobiotics for excretion.

Quiz 36: Drug Development

Describe how certain bacteria can development resistance to penicillin.

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?

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

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

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

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

Briefly describe split-pool synthesis

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 Kd for the RL complex.

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"?

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

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

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.

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

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

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.

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

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

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

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

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

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

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.

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"?

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