Drug Metabolism and Kinetics Quiz
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Questions and Answers

Which organ is primarily responsible for drug metabolism?

  • Intestines
  • Kidneys
  • Liver (correct)
  • Lungs

    • How does drug metabolism generally affect the pharmacologic activity of metabolites compared to their parent compounds?

  • Metabolites usually have lower pharmacologic activity (correct)
  • Metabolites have identical pharmacologic activity
  • Metabolites are always inactive
  • Metabolites have increased pharmacologic activity

    • What is the primary method by which most drugs are eliminated from the body?

  • By metabolism and then urine (correct)
  • By exhalation
  • As unchanged compounds
  • Through saliva

    • What concept describes the elimination of substances at a fixed rate regardless of drug concentration?

    <p>Zero-order kinetics</p> Signup and view all the answers

    Which of the following drugs is eliminated via zero-order kinetics?

    <p>Aspirin in high doses</p> Signup and view all the answers

    What is a significant factor that drug dosing depends on?

    <p>Kidney function</p> Signup and view all the answers

    Which statement about drug metabolism is correct?

    <p>Drug metabolism can increase the polarity of molecules</p> Signup and view all the answers

    What type of kinetics applies when the rate of elimination is directly proportional to serum drug concentration?

    <p>First-order kinetics</p> Signup and view all the answers

    What is the classification of a patient who has little to no functional metabolic activity?

    <p>Poor metabolizer</p> Signup and view all the answers

    Which reaction does NOT typically occur during Phase I drug metabolism?

    <p>Conjugation</p> Signup and view all the answers

    What is the role of Phase II drug metabolism?

    <p>To create more water-soluble compounds</p> Signup and view all the answers

    Which system is primarily involved in Phase I reactions?

    <p>Cytochrome P450 system</p> Signup and view all the answers

    Which of the following is NOT a characteristic of Phase I drug metabolism?

    <p>Usually enhances pharmacologic activity</p> Signup and view all the answers

    What is the relationship between drug concentration and the rate of metabolism for drugs under first-order kinetics?

    <p>It is independent of drug concentration.</p> Signup and view all the answers

    Which of the following is primarily a Phase II enzyme?

    <p>UDP-glucuronosyltransferase</p> Signup and view all the answers

    What occurs in overdoses of drugs that normally follow first-order kinetics?

    <p>Saturable metabolism can occur.</p> Signup and view all the answers

    What is the main purpose of converting lipophilic drugs into more polar molecules during Phase I?

    <p>To aid in excretion</p> Signup and view all the answers

    Which of the following is an example of a substance that follows zero-order kinetics?

    <p>Ethyl alcohol</p> Signup and view all the answers

    Which of the following describes an intermediate metabolizer?

    <p>Patients with reduced metabolic activity</p> Signup and view all the answers

    Where are cytochrome P450 enzymes primarily located in the body?

    <p>Liver and GI tract</p> Signup and view all the answers

    What effect do inducers have on drug metabolism?

    <p>They may increase metabolism of the drug.</p> Signup and view all the answers

    What is a potential consequence of enzyme inhibitors on drug levels?

    <p>They can lead to higher levels of drugs.</p> Signup and view all the answers

    How can genetic variations influence drug metabolism?

    <p>They contribute to altered metabolism of drugs among different racial groups.</p> Signup and view all the answers

    Which enzyme polymorphism is associated with altered metabolism of codeine?

    <p>CYP2D6</p> Signup and view all the answers

    Which of the following is true regarding first-order kinetics?

    <p>The concentration decreases by a constant fraction over time.</p> Signup and view all the answers

    What is the consequence of being a poor metabolizer of CYP2C19 when taking clopidogrel?

    <p>Higher incidence of cardiovascular events</p> Signup and view all the answers

    Which drug is a prodrug that requires metabolism by CYP2C19?

    <p>Clopidogrel</p> Signup and view all the answers

    Which drug listed is known to affect the metabolism of multiple CYP450 enzymes?

    <p>Cimetidine</p> Signup and view all the answers

    What is the effect of genetic variations on CYP450 metabolism?

    <p>They can create poor or ultra-rapid metabolizers.</p> Signup and view all the answers

    Which of the following drugs requires CYP2D6 for its activation?

    <p>Tramadol</p> Signup and view all the answers

    What effect does being an ultra-rapid metabolizer of CYP2D6 have on codeine?

    <p>Increased sensitivity due to higher conversion</p> Signup and view all the answers

    Which of the following drugs is considered a substrate for CYP2C9?

    <p>Miconazole</p> Signup and view all the answers

    Study Notes

    Drug Metabolism

    • Drug metabolism is the process of biotransformation, mainly occurring in the liver, that alters drugs to facilitate elimination
    • Metabolites often have lower pharmacologic activity than the parent compound
    • Metabolism makes drugs more polar for easier elimination
    • Most drugs are eliminated by the kidneys in urine
    • Some drugs are eliminated in bile, saliva, breast milk, or exhaled air

    Kinetics of Metabolism

    • First-order kinetics
      • Rate of metabolism is proportional to the concentration of free drug
      • Constant fraction of drug is metabolized per unit of time (half-life)
      • t1/2 is independent of drug concentration
      • Not saturable in standard doses, but can become saturable in overdoses
    • Zero-order kinetics
      • Constant rate of elimination regardless of drug concentration
      • Examples: Ethanol, Phenytoin, Salicylates, Cisplatin, Fluoxetin, Omeprazol, Aspirin (high doses)

    Cytochrome P450 (CYP450) Enzymes

    • Group of enzymes mainly located in the liver and GI tract
    • Important subcategories include CYP3A4, 2D6, 2C19, and 2C9
    • Can be inhibited or induced by drugs
      • Inducers increase drug metabolism, which can decrease or increase drug activity
      • Inhibitors can lead to higher drug levels and greater potential for adverse drug reactions
    • Enzymes are affected by genetic variations depending on race

    Examples of CYP450 Interactions

    • CYP3A4
      • Inhibitors: Grapefruit juice, Clarithromycin, Erythromycin, Diltiazem, Fluconazole, Ritonavir, Verapamil, Cimetidine
      • Inducers: Phenobarbital, Phenytoin, Rifampicin, St. John's Wort, Glucocorticoids
      • Substrates: Clarithromycin, Erythromycin, Warfarin, Some statins (Itraconazole, Simvastatin)
    • CYP2D6
      • Inhibitors: Fluoxetine, Paroxetine, Bupropion, Quinidine, Amiodarone
      • Inducers: Rifampicin
      • Substrates: B-blockers, TCAs, Tramadol, Codeine
      • Prodrug Substrate: Codeine, Tamoxifen
    • CYP2C19
      • Inhibitors: Lansoprazole, Omeprazole, Fluvoxamine
      • Inducers: Rifampicin, Carbamazepine
      • Substrates: Warfarin, Diazepam, Phenytoin
      • Prodrug Substrate: Clopidogrel
    • CYP2C9
      • Inhibitors: Miconazole, Fluconazole
      • Inducers: Rifampicin, Carbamazepine
      • Substrates: Warfarin, NSAIDs
      • Prodrug Substrate: Losartan
    • CYP2C8
      • Inhibitors: Cimetidine
      • Inducers: Phenobarbital, Rifampicin
      • Substrates: Diazepam
    • CYP1A2
      • Inhibitors: Cimetidine, Ciprofloxacin
      • Inducers: Cigarette smoke
      • Substrates: Theophylline
    • CYP2E1
      • Inhibitors: Disulfiram
      • Inducers: Ethanol, Isoniazid
      • Substrates: Ethanol, Halothane, Isoflurane

    Genetic Variations and CYP450 Polymorphisms

    • Can lead to altered metabolism of drugs
    • Example: CYP2D6
      • Poor metabolizers do not metabolize drugs effectively
      • Ultra-rapid metabolizers metabolize drugs rapidly
      • Codeine is a prodrug that is metabolized to morphine by CYP2D6
      • Poor metabolizers have decreased effects from codeine
      • Ultra-rapid metabolizers may experience large conversion to morphine resulting in high sensitivity
    • Example: CYP2C19
      • Patients with poor CYP2C19 activity have a higher risk of cardiovascular events when taking clopidogrel, an antiplatelet prodrug that relies on CYP2C19 conversion

    Phenotype Classification

    • Ultra-rapid metabolizer (UM): high metabolic activity
    • Extensive metabolizer (EM): normal metabolic activity
    • Intermediate metabolizer (IM): reduced metabolic activity
    • Poor metabolizer (PM): little to no functional metabolic activity

    Reactions of Drug Metabolism

    • Lipophilic drugs are metabolized into more polar hydrophilic substances in the liver
    • Two general sets of reactions: Phase I and Phase II

    Phase I Reactions

    • Occur in the liver
    • Often involve the cytochrome P450 system
    • Convert lipophilic drugs into more polar by introducing or unmasking a polar functional group (e.g., -OH or -NH2)
    • Include reduction, oxidation, or hydrolysis
    • Can increase, decrease, or have no effect on drug activity
    • Phase I reactions not involving P450 include:
      • Amine oxidation (e.g., oxidation of catecholamines or histamine)
      • Alcohol dehydrogenation (e.g., ethanol oxidation)
      • Esterases and hydrolysis

    Phase II Reactions

    • Occur in the liver and kidneys
    • Phase II enzymes are mainly transferases
    • Convert metabolites from Phase I into more water-soluble compounds via conjugation reactions
    • Common substrates for conjugation include:
      • Glucuronic acid
      • Sulfuric acid
      • Acetic acid
      • Amino acids
    • Major phase II enzymes:
      • UDP-glucuronosyltransferases
      • Sulfotransferases
      • N-acetyltransferases
      • Glutathione S-transferases
      • Methyltransferases (mainly thiopurine S-methyl transferase and catechol O-methyl transferase)

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    Pharmacokinetics (Part 3) - University of Baghdad 2024-2025 PDF

    Description

    Test your knowledge on drug metabolism and kinetics, focusing on the biotransformation processes that occur primarily in the liver. Explore the roles of first-order and zero-order kinetics, as well as the significance of cytochrome P450 enzymes in drug elimination. Challenge yourself with questions on metabolites and their pharmacologic activities.

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