10 drug elimination Flashcards
(33 cards)
What is drug metabolism?
The biotransformations that alter the pharmacological activity of both endogenous and exogenous compounds
What do biotransformation do?
Increase hydrophilic character to render metabolites water soluble which aids urinary excretion
What can biotransformation lead to?
A pharmacologically inactive metabolite, a more active species, a less active species or a toxic metabolite
What is a pharmacophore?
The essential components of drug molecules that give it its pharmacological activity
What is deamination?
Removal of an amine group
Give an example of when metabolism causes a more potent metabolite
Codeine O-dealkylation to morphine
What happens to drugs with toxic metabolites?
They are withdrawn - unless cancer treatments
What do phase I reactions do?
Convert parental compound into a more hydrophilic metabolite by adding or unmasking groups
What do phase II reactions do?
They usually involve conjugation with endogenous substrates to further increase aqueous solubility
Where can metabolism occur?
In the liver, epithelial cells of the small intestine, the brain, lung and blood
What are the 4 types of phase I reactions?
Oxidation, reduction, hydrolytic cleavage and isomerization
What is the most common phase I reaction?
Oxidation
What is oxidation?
Adding of oxygen to the drug molecule
What are the 2 types of oxidation reactions?
Oxidation being incorporated into the molecule (hydroxylation) or addition of oxygen causing loss of part of the molecule (deamination)
What is cytochrome P450?
A hemoprotein containing an iron atom which can alternate between the ferrous and ferric states
IS CYP450 an electron acceptor or donor?
Acceptor
Which CYP families are involved in drug metabolism?
CYP1, 2 and 3
What is aromatic hydroxylation?
Addition of OH to aromatic by removal of H to its O and adding the new hydroxyl group to the reactive carbon left behind
What is aliphatic hydroxylation?
Adding of OH to an alkyl group by removing H to its O and adding OH back to reactive carbon
What is O-dealkylation?
Removal of an alkyl group from an oxygen by removing a H to its O, adding the OH back on but causing unstable carbon which will fall off
What is N-dealkylation?
The removal of an alkyl group from nitrogen by removing H, adding it to its O, adding the OH to the carbon causing an unstable carbon which falls off
What does N-dealkylation produce?
Metabolites referred to as nor-metabolites
What does dealkylation produce?
Metabolites referred to as desalkyl metabolites
What is phase II for?
It is the true detoxification step
