Drug Metabolism and Prodrug Strategy Quiz

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Questions and Answers

What is the purpose of drug metabolism?

To convert non-polar drugs into more polar molecules for easier excretion (correct)

To decrease the water solubility of drugs

To increase the shelf life of drugs

To decrease the effectiveness of drugs

Which enzymes are particularly involved in adding polar functional groups to drugs?

Cytochrome P450 enzymes in the liver (correct)

Enzymes in the spleen

Enzymes in the lungs

Enzymes in the kidneys

What class of reactions do phase I reactions fall under in drug metabolism?

Reduction, synthesis, and dehydration

Hydrolysis, esterification, and polymerization

Oxidation, hydration, and condensation

Oxidation, reduction, and hydrolysis (correct)

Why is it necessary to identify all metabolites of a new drug before approval?

To determine the structure and stereochemistry of each metabolite Signup and view all the answers

What happens to polar drugs in the body?

They are quickly excreted by the kidneys Signup and view all the answers

How can non-polar drugs be made more water-soluble for excretion?

By adding polar functional groups through drug metabolism Signup and view all the answers

What is the significance of understanding species-specific metabolic reactions in in vivo studies?

It helps determine which test animals are relevant for drug metabolism tests Signup and view all the answers

What distinguishes regioselective metabolic reactions?

They differentiate between identical functional groups located in different parts of the molecule Signup and view all the answers

What characterizes stereoselective metabolic reactions?

They differentiate between different stereoisomers of chiral molecules Signup and view all the answers

What is the role of cytochrome P450 enzymes in phase I transformations?

They catalyze reactions that introduce one oxygen atom into the drug molecule Signup and view all the answers

How many different families are the cytochrome P450 (CYP) enzymes grouped into?

4 Signup and view all the answers

How are the subfamilies of cytochrome P450 enzymes designated?

By a letter Signup and view all the answers

What type of reaction can cytochrome P450 enzymes catalyze in addition to oxidative reactions?

Reductions Signup and view all the answers

Which enzymes catalyze the hydrolysis of amides and esters respectively?

Esterases and peptidases Signup and view all the answers

Why do amides tend to be hydrolyzed more slowly than esters?

Presence of electron-withdrawing groups Signup and view all the answers

What effect do electron-withdrawing groups have on the susceptibility of amides and esters to hydrolysis?

Increase susceptibility Signup and view all the answers

What can happen to drugs during metabolism in terms of the number of metabolic reactions and resulting metabolites?

Two or more metabolic reactions may occur, resulting in different metabolites Signup and view all the answers

What type of metabolite is formed when hydroxylation occurs on carbon atoms alpha to a heteroatom?

Unstable metabolite that is immediately hydrolysed Signup and view all the answers

Why are tertiary amines more reactive to oxidative dealkylation compared to secondary amines?

Due to their greater basicity Signup and view all the answers

What enzyme deactivates the reactive epoxide formed from the oxidation of alkenes?

Epoxide hydrolase Signup and view all the answers

What is the fate of the epoxide when it evades the enzyme and acts as an alkylating agent?

React with nucleophilic groups in proteins or nucleic acids Signup and view all the answers

What is the intermediate formed when oxidation of an aromatic ring occurs?

Reactive epoxide Signup and view all the answers

What normally forms at the para position when an aromatic ring undergoes rearrangement involving a hydride transfer?

Phenol Signup and view all the answers

What enzyme can deactivate epoxide to form a diol?

Glutathione S-transferase Signup and view all the answers

What happens if the epoxide intermediate evades cytochrome P450 enzymes?

It acts as an alkylating agent and proves toxic Signup and view all the answers

Which functional group can be oxidized to hydroxylamides?

Primary and secondary amides Signup and view all the answers

What process is related to the toxicity of aromatic amines due to the formation of highly electrophilic intermediates?

Oxidation of nitrogen atom Signup and view all the answers

What can aromatic primary amines be methylated into during phase II reaction?

Secondary amines Signup and view all the answers

Which enzyme catalyzes the oxidation of sulfur atom converting thiols into disulphides?

Cytochrome P450 enzymes Signup and view all the answers

Study Notes

Drug Metabolism Purpose and Processes

Drug metabolism transforms lipophilic compounds into hydrophilic forms for easier excretion.
Phase I metabolism primarily involves adding polar functional groups to increase solubility.

Enzymatic Involvement

Cytochrome P450 enzymes (CYP) play a crucial role in introducing polar groups during phase I reactions.
CYP enzymes are categorized into multiple families, each consisting of distinct enzymes.

Phase I Reactions

Phase I reactions involve oxidation, reduction, and hydrolysis, altering the chemical structure of drugs.
Identification of all drug metabolites before approval is essential for assessing safety and efficacy.

Drug Behavior in the Body

Polar drugs are more readily excreted via urine due to higher solubility.
Non-polar drugs can be made more water-soluble through chemical modifications like oxidation or conjugation.

Species-Specific Metabolism

Understanding species-specific metabolic reactions is critical for accurate in vivo study outcomes and safety evaluations.

Metabolic Reaction Characteristics

Regioselective metabolic reactions involve specific metabolic sites on a compound.
Stereoselective metabolic reactions favor the transformation of one stereoisomer over another.

Cytochrome P450 Role

Cytochrome P450 enzymes facilitate a range of reactions, predominantly oxidative transformations.
They also catalyze other reactions, including dealkylation and hydroxylation.

Families and Designation

Cytochrome P450 enzymes are grouped into over 18 families based on amino acid similarity.
Subfamilies are designated with letters to distinguish differences within each family.

Hydrolysis and Reaction Rates

Amides are hydrolyzed more slowly than esters due to their stability and stronger bonding.
Electron-withdrawing groups enhance the susceptibility of amides and esters to hydrolysis.

Metabolic Outcomes

Drugs may undergo multiple metabolic reactions, leading to a variety of metabolites.
Hydroxylation typically yields metabolites at carbon atoms adjacent to heteroatoms.

Reactivity of Amine Types

Tertiary amines are more prone to oxidative dealkylation than secondary amines due to structural factors.

Enzymatic Deactivation

Epoxides are deactivated by enzymes such as epoxide hydrolase, forming less reactive diols.
If epoxide intermediates evade enzymatic deactivation, they can act as alkylating agents.

Aromatic Ring Metabolism

Oxidation of aromatic rings often results in the formation of reactive intermediates, including radical cations.
Rearrangement leads to hydroxymethyl derivatives typically forming at the para position.

Further Transformations

Hydroxylamines can be produced from the oxidation of amines.
Phase II reactions can methylate aromatic primary amines to form less toxic derivatives.

Sulfur Oxidation

Thiol groups are oxidized to disulphides by specific oxidizing enzymes, impacting drug activity and toxicity profiles.

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Description

Test your knowledge on drug metabolism and the prodrug strategy used to activate drugs in the body. Learn about the requirements for identifying metabolites of new drugs, determining their structure and stereochemistry, and testing for biological activity.