8- Drug Elimination Flashcards
(46 cards)
What is the purpose of biotransformations in terms of Metabolism
Alters the pharmacological activity by increasing hydrophilic character to render metabolites water soluble which aids
What are polar, hydrophilic groups
OH NH2 COOH
What are examples of Non-Polar, Hydrophobic groups
CH2, CH3 C6H5
What are the two ways the hydrophilicity of a molecule
By introducing or unmasking polar functional groups into the molecule.
By removing non-polar functional groups into the molecule.
What will happen to terbutaline if it goes through oxidative deamination.
Removal of an amine group via a CYP450 enzyme.
What will happen to codeine if it goes through oxidative O-dealkylation.
An alkyl group will be removed from an oxygen molecule via a CYP450 enzyme.
What would happen to propranolol if it goes through N-dealkylation
The removal of an alkyl group from a nitrogen group via a CYP450 enzyme.
What are Phase 1 reactions of drug metabolism
Covert parent compound into a more hydrophillic metabolite by adding or unmasking functional groups.
Oxidation
Reduction
Hydrolytic Cleavage
Isomerization
What are phase 2 reactions of metabolism
Conjugation with endogenous substrate to further increase aqueous solubility.
Via glucuronidation, salvation, amidation
What is the major organ for drug metabolism
The liver
What processes do extrahepatic microsomal enzymes put drugs through and where are they found
Found in the digestive system, put through oxidation, conjugation and hydrolysis.
What are examples of processes that hepatic microsomal enzymes would put drug through.
Oxidation, Conjugation
What are examples of processes that hepatic non-microsomal enzymes would put drug through
Sulfation, GSH, Alcohol/aldehyde dehydrogenase, hydrolysis, ox/reduct
What are the two types of oxidation reactions
N-dealkylation O-dealkylation
What is cytochrome p450
A hemoprotein containing an iron atom which can alternate between ferrous and ferric states.
Electron acceptor
Where is Cytochrome p450 found.
Found mainly in the liver but sometimes the lungs.
What cytochrome isoform is used in ibuprofen metabolism.
CYP450 2D6
How does CYP450 metabolise drugs
The drug substrate enters the binding site of CYP450.
The haem co-factor transfers oxygen onto drug molecule.
Therefore making it more polar.
What are the steps of aromatic hydroxylation by CYP450
Substrate needs a C-H for the P450 to cleave
H transferred onto P450- Fe-O to form a hydroxide
OH transferred from p450 back to substrate where original CH was cleaved
What is the process of aromatic hydroxylation via CYP450 enzymes.
Substrate needs a C-H for P450 to cleave.
H transferred onto P450- Fe-O to form hydroxide
OH transferred from P450 back to substrate where original CH was cleaved
What is the process of O-dealkylation of ethers via a CYP450 enzyme
Substrate needs a CH for P450 to cleave
H transferred onto P450 Fe-O to form a hydroxide
OH transferred from P450 back to substrate where original CH was cleaved
What is the name for the functional group that forms after O-dealkylation of ethers and N-dealkylation of amines
Hemi-acetal
What happens to the Semi-Acetal group during O-dealkylation of ethers
C between two heteroatoms is unstable and breaks down
The alkyl group is removed as an aldehyde
What is the process of N-dealkylation of amines via a CYP450 enzyme
Substrate needs a C-H for P450 to cleave
H transferred onto P450-Fe-O to form hydroxide
OH transferred from P450 back to substrate where original C-H was cleaved
The C bond becomes unstable and breaks releasing the acetyl group as an aldehyde.
