Phase I CYP450 Oxidation Flashcards
What is the purpose of drug metabolism?
Drug metabolism converts lipophilic drugs into hydrophilic metabolites, facilitating their excretion through urine or feces.
What are the two phases of drug metabolism?
Phase I involves functionalization reactions like oxidation, reduction, and hydrolysis. Phase II involves conjugation reactions to increase solubility for excretion.
What is the main enzyme family involved in Phase I metabolism?
The cytochrome P450 (CYP450) enzyme family, primarily found in the liver, plays a central role in Phase I oxidation reactions.
What is the role of CYP450 enzymes?
CYP450 enzymes introduce a functional group to the drug molecule through oxidation, preparing it for Phase II metabolism or excretion.
What are the key components required for CYP450 activity?
CYP450 activity requires molecular oxygen (O₂), NADPH, and cytochrome P450 reductase.
What is aliphatic hydroxylation?
Aliphatic hydroxylation involves adding an -OH group to a saturated carbon chain, as seen in the metabolism of tolbutamide to an alcohol metabolite.
What is aromatic hydroxylation?
Aromatic hydroxylation adds an -OH group to an aromatic ring, such as the conversion of salicylic acid to gentisic acid.
What is epoxidation?
Epoxidation forms an epoxide by adding an oxygen atom to a double bond, as observed in carbamazepine metabolism to carbamazepine epoxide.
What are examples of epoxidation?
“Examples include the conversion of carbamazepine to carbamazepine epoxide.”
What is O-dealkylation?
O-dealkylation removes an alkyl group from an ether, producing an alcohol and formaldehyde, as seen in codeine metabolism to morphine.
What are examples of O-dealkylation?
“Codeine is metabolized to morphine through O-dealkylation, producing formaldehyde as a by-product.”
What is N-dealkylation?
N-dealkylation removes an alkyl group from an amine, forming an amine and formaldehyde, such as diazepam metabolism to nordiazepam.
What are examples of N-dealkylation?
“Diazepam is metabolized to nordiazepam, with formaldehyde produced as a by-product.”
What is deamination?
Deamination removes an amino group from a molecule, producing an inactive metabolite and ammonia, as seen in amphetamine metabolism.
What are examples of deamination?
“Amphetamine metabolism involves deamination, yielding an inactive metabolite and ammonia.”
What is N-oxidation?
N-oxidation involves adding an oxygen atom to a nitrogen atom, producing a hydroxylamine, such as clozapine metabolism to clozapine N-oxide.
What are examples of N-oxidation?
“Clozapine is metabolized to clozapine N-oxide through N-oxidation.”
What is S-oxidation?
S-oxidation introduces an oxygen atom to a sulfur atom, forming a sulfoxide or sulfone, commonly seen in sulfide-containing drugs.
What are examples of S-oxidation?
“Sulfoxides are formed from sulfides during S-oxidation, although specific drug examples were not provided in detail.”
What is alcohol oxidation?
Alcohol oxidation converts alcohols into aldehydes or ketones, as seen in ethanol metabolism to acetaldehyde.
What are examples of alcohol oxidation?
“Ethanol is oxidized to acetaldehyde during alcohol oxidation.”
What is dehydrogenation?
Dehydrogenation removes hydrogen atoms, forming a double bond or cyclic structure, such as paracetamol metabolism to NAPQI.
What are examples of dehydrogenation?
“Paracetamol is dehydrogenated to NAPQI, a toxic metabolite.”
What is dehalogenation?
“Dehalogenation removes a halogen atom, often from haloalkanes, as seen in halothane metabolism.”
What are examples of dehalogenation?
“Halothane is metabolized through dehalogenation.”
What is the clinical significance of CYP450 isoforms?
CYP450 isoforms, such as CYP3A4, CYP2D6, and CYP2C9, metabolize most clinically used drugs. Variability in isoform activity can affect drug efficacy and toxicity.
What is first-pass metabolism?
First-pass metabolism occurs when orally administered drugs are metabolized by the liver before reaching systemic circulation, reducing bioavailability.
What is the role of CYP450 in drug-drug interactions?
CYP450 enzymes can be inhibited or induced by drugs, altering the metabolism of co-administered drugs and potentially causing toxicity or therapeutic failure.
