Pharmacokinetics III Flashcards
What is the goal of bio transformation and metabolism of drugs xenobiotics?
Promote their elimination from the body
What does the bio transformation of drugs convert lip soluble, non-ionized compounds to?
Water soluble, ionized metabolites
If a drugs molecular weight is <350, what organ excretes it?
Kidney
If a drugs molecular weight is >350, what is it excreted in?
Bile
Where does most metabolism occur?
Liver
What is an example of a drug that needs to be metabolized to be active? What is its active metabolite?
Codeine
Morphine
What is an example of a metabolite that is more active than the parents drug?
Parent drug diazepam is converted to nordiazepam and then to oxazepam
What is an example of a drug that is metabolized to toxic metabolites? What is the toxic metabolite?
Acetaminophen
N-acetyl-p-benzo-quinone imine
In acetaminophen metabolism, the increased production of metabolites leads to what?
Oxidative stress and hepatotoxicity
Ethanol induces acetaminophen metabolism through what?
CYP2E1
What is phase 1 of bio transformation reactions?
Convert lip soluble , non-ionized compounds to more ionized, hydrophilic metabolites
What is phase II of biotransformation reaction?
It adds an ionized, charged particle to a phase I metabolite to form a more polar and hydrophilic conjugate
What type of phase I reactions are most common?
Oxidation
Are phase I reactions compound specific?
There are no specific enzymes metabolizing a particular drug
Enzymes instead INTRODUCE or MASK specific functional groups or bonds of multiple drugs
What kind of phase I enzymes are inducible ?
Microsomal (CYP450s)
What is the function of CYP450s?
Microsomal enzymes in the liver that oxidase drugs, acting as a handle for phase II conjugation
What P450 subtype metabolizes > 50% of drugs
3A4
What is the ONLY phase II enzyme that is inducible?
Glucuronyl transferase