Phase I CYP450 Oxidation

Question 1

What is the purpose of drug metabolism?

Answer 1

Drug metabolism converts lipophilic drugs into hydrophilic metabolites, facilitating their excretion through urine or feces.

Question 2

What are the two phases of drug metabolism?

Answer 2

Phase I involves functionalization reactions like oxidation, reduction, and hydrolysis. Phase II involves conjugation reactions to increase solubility for excretion.

Question 3

What is the main enzyme family involved in Phase I metabolism?

Answer 3

The cytochrome P450 (CYP450) enzyme family, primarily found in the liver, plays a central role in Phase I oxidation reactions.

Question 4

What is the role of CYP450 enzymes?

Answer 4

CYP450 enzymes introduce a functional group to the drug molecule through oxidation, preparing it for Phase II metabolism or excretion.

Question 5

What are the key components required for CYP450 activity?

Answer 5

CYP450 activity requires molecular oxygen (O₂), NADPH, and cytochrome P450 reductase.

Question 6

What is aliphatic hydroxylation?

Answer 6

Aliphatic hydroxylation involves adding an -OH group to a saturated carbon chain, as seen in the metabolism of tolbutamide to an alcohol metabolite.

Question 7

What is aromatic hydroxylation?

Answer 7

Aromatic hydroxylation adds an -OH group to an aromatic ring, such as the conversion of salicylic acid to gentisic acid.

Question 8

What is epoxidation?

Answer 8

Epoxidation forms an epoxide by adding an oxygen atom to a double bond, as observed in carbamazepine metabolism to carbamazepine epoxide.

Question 9

What are examples of epoxidation?

Answer 9

“Examples include the conversion of carbamazepine to carbamazepine epoxide.”

Question 10

What is O-dealkylation?

Answer 10

O-dealkylation removes an alkyl group from an ether, producing an alcohol and formaldehyde, as seen in codeine metabolism to morphine.

Question 11

What are examples of O-dealkylation?

Answer 11

“Codeine is metabolized to morphine through O-dealkylation, producing formaldehyde as a by-product.”

Question 12

What is N-dealkylation?

Answer 12

N-dealkylation removes an alkyl group from an amine, forming an amine and formaldehyde, such as diazepam metabolism to nordiazepam.

Question 13

What are examples of N-dealkylation?

Answer 13

“Diazepam is metabolized to nordiazepam, with formaldehyde produced as a by-product.”

Question 14

What is deamination?

Answer 14

Deamination removes an amino group from a molecule, producing an inactive metabolite and ammonia, as seen in amphetamine metabolism.

Question 15

What are examples of deamination?

Answer 15

“Amphetamine metabolism involves deamination, yielding an inactive metabolite and ammonia.”

Question 16

What is N-oxidation?

Answer 16

N-oxidation involves adding an oxygen atom to a nitrogen atom, producing a hydroxylamine, such as clozapine metabolism to clozapine N-oxide.

Question 17

What are examples of N-oxidation?

Answer 17

“Clozapine is metabolized to clozapine N-oxide through N-oxidation.”

Question 18

What is S-oxidation?

Answer 18

S-oxidation introduces an oxygen atom to a sulfur atom, forming a sulfoxide or sulfone, commonly seen in sulfide-containing drugs.

Question 19

What are examples of S-oxidation?

Answer 19

“Sulfoxides are formed from sulfides during S-oxidation, although specific drug examples were not provided in detail.”

Question 20

What is alcohol oxidation?

Answer 20

Alcohol oxidation converts alcohols into aldehydes or ketones, as seen in ethanol metabolism to acetaldehyde.

Question 21

What are examples of alcohol oxidation?

Answer 21

“Ethanol is oxidized to acetaldehyde during alcohol oxidation.”

Question 22

What is dehydrogenation?

Answer 22

Dehydrogenation removes hydrogen atoms, forming a double bond or cyclic structure, such as paracetamol metabolism to NAPQI.

Question 23

What are examples of dehydrogenation?

Answer 23

“Paracetamol is dehydrogenated to NAPQI, a toxic metabolite.”

Question 24

What is dehalogenation?

Answer 24

“Dehalogenation removes a halogen atom, often from haloalkanes, as seen in halothane metabolism.”

Question 25

What are examples of dehalogenation?

Answer 25

“Halothane is metabolized through dehalogenation.”

Question 26

What is the clinical significance of CYP450 isoforms?

Answer 26

CYP450 isoforms, such as CYP3A4, CYP2D6, and CYP2C9, metabolize most clinically used drugs. Variability in isoform activity can affect drug efficacy and toxicity.

Question 27

What is first-pass metabolism?

Answer 27

First-pass metabolism occurs when orally administered drugs are metabolized by the liver before reaching systemic circulation, reducing bioavailability.

Question 28

What is the role of CYP450 in drug-drug interactions?

Answer 28

CYP450 enzymes can be inhibited or induced by drugs, altering the metabolism of co-administered drugs and potentially causing toxicity or therapeutic failure.