Pharmacology · MU Sofia

7. Drug Metabolism

Explains how living organisms chemically modify drugs, turning lipophilic compounds into excretable hydrophilic products, mainly in the liver. It then separates Phase I functionalisation (oxidation, reduction, hydrolysis) from Phase II conjugation, with the enzymes and an example for each. It closes with genetic, age, sex, diet, disease and drug-interaction factors, including enzyme induction and inhibition, and five recap questions.

Inside: 3 sections · 6 labelled pictures · 10 flashcards · 4 min

Topic 7 of 93 in the MU Sofia syllabus for Pharmacology (Dental Medicine, Year 3). The free AceMed note covers it in 3 sections, about 593 words (4 min of reading), with 10 flashcards.

In this note

  1. Drug Metabolism
  2. Factors Affecting Drug Metabolism
  3. Recap Questions -

Drug Metabolism

Drug metabolism refers to the biochemical modification of pharmaceutical substances by living organisms, typically through specialized enzymatic systems. The primary purpose of drug metabolism is to convert lipophilic chemical compounds into more readily excretable hydrophilic products. This process generally occurs in the liver, although other tissues and organs (e.g., kidneys, intestines, lungs) can also be involved. Drug metabolism is essential for the detoxification and elimination of drugs from the body.

Phases of Drug Metabolism

Phase I: Functionalization Reactions

Phase I reactions introduce or expose functional groups on the drug molecule. These reactions include oxidation, reduction, and hydrolysis, primarily catalyzed by enzymes such as cytochrome P450 (CYP) enzymes, monoamine oxidase, and alcohol dehydrogenase.

  1. 1. Oxidation
  • Involves the addition of oxygen or the removal of hydrogen.
  • Catalyzed by cytochrome P450 enzymes (e.g., CYP3A4, CYP2D6).
  • Example: The oxidation of ethanol to acetaldehyde by alcohol dehydrogenase.
  1. 2. Reduction
  • Involves the addition of hydrogen or the removal of oxygen.
  • Often occurs under low-oxygen conditions.
  • Example: The reduction of nitroglycerin to release nitric oxide.
  1. 3. Hydrolysis
  • Involves the cleavage of bonds by the addition of water.
  • Catalyzed by esterases and amidases.
  • Example: The hydrolysis of aspirin to salicylic acid and acetic acid.

Phase II: Conjugation Reactions

Phase II reactions involve the conjugation of the drug or its Phase I metabolites with endogenous substrates, making the compound more water-soluble and easier to excrete. These reactions are catalyzed by transferase enzymes.

  1. 1. Glucuronidation
  • Conjugation with glucuronic acid.
  • Catalyzed by UDP-glucuronosyltransferases (UGTs).
  • Example: The glucuronidation of bilirubin.
  1. 2. Sulfation
  • Conjugation with sulfate groups.
  • Catalyzed by sulfotransferases (SULTs).
  • Example: The sulfation of acetaminophen.
  1. 3. Acetylation
  • Conjugation with acetyl groups.
  • Catalyzed by N-acetyltransferases (NATs).
  • Example: The acetylation of isoniazid.
  1. 4. Glutathione Conjugation
  • Conjugation with glutathione, aiding in detoxification.
  • Catalyzed by glutathione-S-transferases (GSTs).
  • Example: Detoxification of reactive intermediates formed by Phase I metabolism.
  1. 5. Methylation
  • Conjugation with methyl groups.
  • Catalyzed by methyltransferases.
  • Example: The methylation of catecholamines.

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