Metabolism
conversion of one substance into another substance in the body
more polar
The goal of metabolism is to rid the body of foreign compounds (xenobiotic) by making ____ products
Liver, intestine, kidney, lung, other tissues
Drugs undergo chemical changes in the body by enzymes produced by what organs?
Metabolitess
Products of metabolism
Detoxification
-metabolites are inactive
-metabolites are less toxic
Bioactivation
-metabolites are more active
-metabolites are more toxic
Phase I
-introduces new functional groups
-modifies existing functional groups
-creates substrates for phase II
-Enhances polarity and solubility
Phase II
-conjugation and elimination
-conjugation of drug or metabolite
-conjugation adds an additional group
Oxidation, dealkylation, deamination, reduction, hydrolysis
Phase I metabolism will include what type of chemical reactions?
glucuronidation, sulfation, acetylation, methylation
Phase II metabolism will include what type of chemical reactions?
First pass metabolism
drugs metabolized by liver or extra hepatic tissue before reaching systemic circulation
CYP450
most common and important type of biotransformation
True
Most drugs are metabolized by CYP3A4. T/f?
Electron withdrawing
reduce aromatic oxidation
Electron donating
enhances para- and ortho-oxidation
Oxidation
-makes highly polar products for elimination
NADPH
Reduction reactions require what chemical?
Prodrugs
-carboxylic acid containing drugs that have a difficult time crossing membranes at some pHs
- these are ester derivatives that are inactive
esterases
carboxylic acid is released by ____
Phase 2 reactions
-conjugate functional groups that were created during Phase I are already present on parent drug
-inactivate the drug in most cases
elimination in urine or bile
Phase II reactions all lead to what?
Glucuronidation
-most common reaction to form water soluble metabolites
-primarily excreted by kidneys, sometimes GI tract with bile
Sulfation & Glucuronidation
What are the primary metabolic reactions in first pass metabolism?
CYP3A4
found in intestinal mucosa and affects oral bioavailability of many drugs
-OH, -COOH, -NH2, -SH
Which functional groups symbolize oxidation, reduction, or hydrolysis?
endoplasmic reticulum
Where is CYP450 located?
CYP 1, 2, 3
Which enzymes in the CYP family are involved in drug metabolism?
NADPH & O2
CYP450 enzyme requires what molecules?
intestinal mucosa
Where is CYP3A4 located?