Formation of low mass protostars and their circumstellar disks
Drug Metabolism: An Overview of Sites, Stages and Enzymes
1.
2. Drug metabolism is a biochemical modification
of pharmaceutical substances by living
organisms usually through specialized enzymatic
activity.
3. Drug Metabolism does-
metabolism of drugs into more hydrophilic
metabolites
Generates more polar (water soluble), inactive
metabolites.
4. Site of Biotransformation
Rough Endoplasmic Reticulum and cytosol
Enzymes concentratedly localized in Hepatocytes in
Liver.
Other organs with significant metabolic capacity are
GI tract, kidneys and lungs.
5. Stages of drug metabolism
Absorption
Distribution
Metabolism
Elimination
8. Cytochrome P450 Nomencleature
17 families (CYPs) –
sequences > 40% identical (identified by numeric
number)
CYP1, CYP2
further into subfamilies –
sequences >55% identical (identified by a letter)
CYP1A, CYP2D
different isoforms – (identified by another numeric
number)
CYP2D6, CYP3A4
9. Occurs mostly in cytosol.
Covalent bonding is formed between a functional
group metabolite and an endogenous substrate.
Highly polar – rapidly excreted in urine.
Usually inactive
except : morphine 6-glucuronide
Phase II (conjugation reactions)
True detoxification of drugs
10. Factors affecting Drug Metabolism
Environmental Factors:
Induction
Inhibition
Disease Factors
Age and Sex
Genetic Variation
drug gets into bloodstream
gets to site of action
is “changed” so that it can be excreted
- leaves the body
(Superfamily of heme containing proteins)
Main function of Phase I metabolism is to prepare the compound for phase II metabolism
Converts the parent drug to a more polar metabolites by introducing or unmasking a functional group (-OH,- NH2 ,-SH).
Usually results in loss of pharmacological activity
Sometimes may be equally or more active than parent
The final product usually contains a chemical reactive functional group OH, NH2 , SH, COOH.
This functional group can be acted upon by the phase II or conjugative enzymes.
Main function of Phase I metabolism is to prepare the compound for phase II metabolism not for excretion.
such as glucuronic acid, sulfate, acetate, or an amino acid.
Gives products that are generally water soluble and easily excreted
Includes sugar conjugation, sulfation, methylation, acetylation, amino acid conjugation, glutathione conjugation