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    Metabolic Changes of Drugs and Related Organic Compounds

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    Micah Lou Calamba
    This chapter discusses drug metabolism and biotransformation. It describes the various phases of drug metabolism, including phase I reactions like oxidation, reduction, and hydrolysis that make the drug more polar. Phase II or conjugation reactions then combine these metabolites with endogenous compounds like glucuronic acid, glutathione, sulfate, or acetyl groups via transferase enzymes to further increase polarity and allow excretion. The key conjugation reactions are glucuronidation, acetylation, glutathione conjugation, sulfation, and methylation. Understanding how drugs are metabolized helps explain interactions between drugs and individual variability in drug responses.

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    Metabolic Changes of Drugs and Related Organic Compounds

    Uploaded by

    Micah Lou Calamba
    23 views20 pages
    This chapter discusses drug metabolism and biotransformation. It describes the various phases of drug metabolism, including phase I reactions like oxidation, reduction, and hydrolysis that make the drug more polar. Phase II or conjugation reactions then combine these metabolites with endogenous compounds like glucuronic acid, glutathione, sulfate, or acetyl groups via transferase enzymes to further increase polarity and allow excretion. The key conjugation reactions are glucuronidation, acetylation, glutathione conjugation, sulfation, and methylation. Understanding how drugs are metabolized helps explain interactions between drugs and individual variability in drug responses.

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    This chapter discusses drug metabolism and biotransformation. It describes the various phases of drug metabolism, including phase I reactions like oxidation, reduction, and hydrolysis that make the drug more polar. Phase II or conjugation reactions then combine these metabolites with endogenous compounds like glucuronic acid, glutathione, sulfate, or acetyl groups via transferase enzymes to further increase polarity and allow excretion. The key conjugation reactions are glucuronidation, acetylation, glutathione conjugation, sulfation, and methylation. Understanding how drugs are metabolized helps explain interactions between drugs and individual variability in drug responses.

    Copyright:

    © All Rights Reserved
    Download as PPTX, PDF, TXT or read online from Scribd
    Download as pptx, pdf, or txt
    23 views20 pages

    Metabolic Changes of Drugs and Related Organic Compounds

    Uploaded by

    Micah Lou Calamba
    This chapter discusses drug metabolism and biotransformation. It describes the various phases of drug metabolism, including phase I reactions like oxidation, reduction, and hydrolysis that make the drug more polar. Phase II or conjugation reactions then combine these metabolites with endogenous compounds like glucuronic acid, glutathione, sulfate, or acetyl groups via transferase enzymes to further increase polarity and allow excretion. The key conjugation reactions are glucuronidation, acetylation, glutathione conjugation, sulfation, and methylation. Understanding how drugs are metabolized helps explain interactions between drugs and individual variability in drug responses.

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    © All Rights Reserved
    Download as PPTX, PDF, TXT or read online from Scribd
    Download as pptx, pdf, or txt
    of 20

    Chapter 3

    METABOLIC CHANGES OF DRUGS AND


    RELATED ORGANIC COMPOUNDS

    OBJECTIVES
     To identify the site of biotransformation of drug
     To describe various phases of drug metabolism
     To understand why certain drugs are contradicted with other drugs
     To become aware of the metabolism currently used therapeutic
    agents
    Drug Metabolism

     The biochemical changes that occur on drugs or other foreign


    compounds, the purpose of which is to facilitate elimination.
     Without it, xenobiotics can remain indefinitely in the body.
     It may lead to the formation of inactive and non toxic
    compounds, hence the term detoxification .
     However, more recent studies have shown that some
    metabolites are not only active but toxic.
    PRODUCT OF METABOLISM

    PRORUGS/MET XENOBIOTICS
    Must be
    ABOLITES
    converted to
    Are mostly
    a water
    lipophilic or
    soluble
    lipid soluble substance(hyd
    compounds rophilic)
    Phase II or Conjugation reaction
     Phase II or conjugation (latin, conjugatus = yoked together)
    reactions involve combination of a drug or its PHASE I metabolite
    with an endogenous substance to form a highly polar product,
    w/c can be efficiently excreted in the body.
     Uses enzymes (transferases) to attach small endogenous polar
    molecules to a drug.
     these endogenous compounds are:
    *GLUCORONIDATION
    *ACETYLATION
    *GLUTATHIONE
    * SULFATION
    *METHYLATION
    Phase II or Conjugation reaction
    * Involves the following conjugation reactions that are catalyzed by transferase
    enzymes: GLUCORONIDATION, ACETYLATION, GLUTATHIONE, SULFATION and
    METHYLATION
    Type of Endogenous Transferase Types of substrates Examples
    conjugation reactant (enzymes)
    UDP glucuronic UDP Phenol and Morphine,
    acid (UDPGA) glucuronyltransfer alcohol, acetaminophen,
    Glucuronidati a- carboxylic acids, diazepam,
    on se hydroxylamides, digitoxin, digoxin
    sulfonamides

    Acetylation Acetyl-Coa N-
    Acetyltransferase
    Amines Sulphonamides,
    isoniazid,
    clonezepam,
    dapsone,
    mescaline

    Glutathione Glutathione GSH-S-transferase Epoxides, arene


    oxides, nitro
    Acetaminophen,
    bromobenzene
    (GSH)
    groups,
    Hydroxylamines

    Sulfation Phosphoadenosyl
    phosphosulfate
    Sulfotransferase Phenols, alcohols,
    Aromatic amines
    Aniline, phenol,
    acetaminophen,
    Glucuronidation (Glucuronic acid
    conjugation)
    • Readily available of supply of D-glucuronic acid
    (derived from d glucose)
    • Numerous functional group that can combine
    enzymatically with glucuronic acid when attached to
    xenobiotic substrates, greatly increases the water
    solubility of the conjugated product.
    • Phenolic and alcoholic hydroxyls are the most
    common functional groups undergoing
    glucuronidation in drug metabolism.
     Morphine, acetaminophen and p-hydroxyphenytoin are a few
    examples
    of phenolic compounds that undergo considerable glucuronidation.

    Arrows indicate
    sites of B-
    glucuronide
     Alcoholic hydroxyls, such as those present in trichloroethanol,
    attachment
    chloramphenicol and propranolol are conjugated.
    Glucuronic acid conjugation or
    Glucuronidation
     A drug must have a group capable of forming bond
    with the endogenous compound.
    Sulfation (sulphate conjugation)

     Occurs primarily for phenols and occasionally for


    alcohols, aromatic amines and N-hydroxyl
    compounds
     Catalyzed by sulfotransferase enzyme
    Glutathione (Mercapturic Acid)

    •
    • Its conjugation is catalyzed by an enzyme
    known as glutathione S-transferase.
    •
    • Degradation of GSH is due to renal and
    hepatic microsomal enzymes
    •
    ACETYLATION

     Derivatives formed from these amino functionalities are inactive


    and non-toxic.
     Less water solubility
     Its primary function is the termination of pharmacological activity
    and detoxification
     Acetyl group used is acetyl-CoA
    METHYLATION

     Most of the products end up


    pharmacologically inactive
     Adding methyl groups to endogenous
    compound
     Catalyzed by enzyme transmethylases
    METHYLATION

    Foreign compounds that undergo methylation


    includes:
     Cathecols,phenols,amines and N-
    heterocyclic and thiol compounds.
     Antihypertensive drugs (methyldopa)
     Antiparkinsonism agent (levodopa)
     Norephenephrine and Dopamine

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