Ch8 DRUG METABOLISM Flashcards
metabolism/biotransformation
the chemical alteration of a drug in a body as the body works to excrete the drug
The main organ that metabolizes drugs is?
the liver, but the kidneys and gut wall also metabolize drugs.
Biotransformation Phase I
the drugs are oxidized and have a functional group added to them
enzymes that carry out phase I reactions
cytochromes (CYPs) - there are at least 12 CYPs that are important for drug metabolism.
xenobiotics
exogenous chemicals that enter the body - often as food - can have reactions with CYPs
why do cytochromes contain a heme group?
the heme group binds O2, which carries out the phase 1 oxidization reaction
Reaction of CYPs with xenobiotics
can lead to drug interactions. The most common of these occurs when two drugs that are metabolized by the same CYP interfere with one another and there is a decrease in metabolism
enzyme induction
Exposure of a CYP to a xenobiotic can also cause more of the enzyme to be produced
This will have the opposite effect of blockade and will increase the rate of breakdown of that xenobiotic and other chemicals that are metabolized by that enzyme
Induction of enzymes is far less common than blockade and takes days to
weeks to occur
Hydrolysis
the addition of a water molecule to another molecule leads to the breakdown of that molecule.
Ester groups can by hydrolyzed; enzymes that carry out the hydrolysis are esterases.
Prodrugs
A prodrug is a pharmacological substance that is inactive when taken in and is then activated by metabolism in a process called bioactivation. This activation is usually due to CYP enzymes
Phase 2 - Conjugation
one or more molecules are added to a drug molecule or its metabolite. Adding to the original molecule leads to greater water solubility, and the molecule can then be more easily excreted in the bile or by the kidneys
enzymes that are involved in phase II
enzyme is called transferases because they transfer the conjugating group from the enzyme to the drug or metabolite.
For example, the enzyme involved in conjugation with glucuronic acid is called glucuronyl transferase
