Liver – detoxification & excretion
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Questions and Answers

What is the principal organ responsible for drug metabolism?

  • Lungs
  • Liver (correct)
  • Heart
  • Kidneys

    • Which phase of drug metabolism involves the introduction of functional groups to increase polarity?

  • Phase IV
  • Phase II
  • Phase III
  • Phase I (correct)

    • Which of the following processes is NOT part of Phase I metabolic reactions?

  • Dealkylation
  • Glucuronidation (correct)
  • Oxidation
  • Hydrolysis

    • What is the primary consequence of drug metabolism?

    <p>Drugs can be excreted in a form that is more suitable for elimination.</p> Signup and view all the answers

    Which type of drugs are primarily converted into hydrophilic metabolites to enhance excretion?

    <p>Lipophilic drugs</p> Signup and view all the answers

    Which of the following describes Phase II metabolic reactions?

    <p>Combines substrate with various acids to form polar conjugates.</p> Signup and view all the answers

    Which enzyme family is most associated with Phase I oxidation reactions?

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

    What is the major function of Phase I metabolism?

    <p>Prepare drugs for Phase II metabolism.</p> Signup and view all the answers

    What enzyme is responsible for oxidizing ethanol to acetaldehyde?

    <p>Alcohol dehydrogenase (ADH)</p> Signup and view all the answers

    Which substance is irreversibly inhibited by Disulphiram in the context of alcohol metabolism?

    <p>Aldehyde dehydrogenase (ALDH)</p> Signup and view all the answers

    What is the key function of Phase I reactions in drug metabolism?

    <p>To prepare drugs for Phase II detoxification</p> Signup and view all the answers

    In the metabolism of paracetamol, what is the primary Phase II pathway?

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

    Which metabolite is produced from the oxidative dealkylation of codeine?

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

    What type of reaction does hydrolysis represent in drug metabolism?

    <p>Addition of water leading to bond cleavage</p> Signup and view all the answers

    What condition leads to the saturation of the glutathione pathway when overdose occurs?

    <p>High doses of paracetamol</p> Signup and view all the answers

    Which of the following is not a common conjugation reaction found in Phase II metabolism?

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

    Which functional group does sulfonation typically target during Phase II metabolism?

    <p>Hydroxyl groups</p> Signup and view all the answers

    What happens to acetaldehyde when Disulphiram is administered?

    <p>It accumulates in the body</p> Signup and view all the answers

    In the Phase I metabolism of ethanol, what is the product of the first enzymatic reaction?

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

    Chloramphenicol's mechanism in drug metabolism involves which type of reaction?

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

    What type of chemical reaction does glucuronidation represent in the context of drug metabolism?

    <p>Addition of a hydrophilic group</p> Signup and view all the answers

    What is the main purpose of drug metabolism in the body?

    <p>To convert lipophilic drugs into hydrophilic metabolites for excretion</p> Signup and view all the answers

    Which organ is the principal site of drug metabolism?

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

    Which of the following is NOT a consequence of drug metabolism?

    <p>Drug is converted into a toxic compound by the liver</p> Signup and view all the answers

    What term describes an inactive compound that is converted into an active drug by metabolism?

    <p>Pro-drug</p> Signup and view all the answers

    How does metabolism affect renal excretion of drugs?

    <p>It increases water solubility, enhancing renal excretion</p> Signup and view all the answers

    Which of the following tissues is NOT typically involved in drug metabolism?

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

    Phase I drug metabolism typically involves which type of reactions?

    <p>Oxidation, reduction, hydrolysis</p> Signup and view all the answers

    Phase II drug metabolism primarily involves:

    <p>Conjugation of metabolites to make them more hydrophilic</p> Signup and view all the answers

    Phase II drug metabolism primarily involves:

    <p>Conjugation of metabolites to make them more hydrophilic</p> Signup and view all the answers

    Which of the following describes an outcome where drug metabolism produces a metabolite with its own pharmacological activity?

    <p>Active metabolite formation</p> Signup and view all the answers

    Why are lipophilic drugs less likely to be excreted unchanged?

    <p>Lipophilic drugs are reabsorbed in the renal tubules</p> Signup and view all the answers

    Which enzyme system is the most important in the metabolism of drugs in the liver?

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

    Which of the following may occur when an inactive pro-drug is metabolized?

    <p>The drug is converted into an active form</p> Signup and view all the answers

    What is the main function of Phase I in drug metabolism?

    <p>To introduce or unmask a functional group to make the drug more polar</p> Signup and view all the answers

    Which of the following is a common reaction in Phase I metabolism?

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

    Phase I metabolic reactions are primarily catalyzed by which enzyme family?

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

    Where are Cytochrome P450 enzymes predominantly located in hepatocytes?

    <p>Endoplasmic reticulum</p> Signup and view all the answers

    Where are Cytochrome P450 enzymes predominantly located in hepatocytes?

    <p>Endoplasmic reticulum</p> Signup and view all the answers

    What occurs in Phase II metabolism?

    <p>Conjugation of drugs with polar molecules like glucuronic acid or sulfate</p> Signup and view all the answers

    Which of the following reactions is a Phase II metabolic process?

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

    Where are the enzymes responsible for Phase II metabolism mainly located?

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

    What is the primary goal of Phase II reactions in drug metabolism?

    <p>To form polar conjugates that are easily excreted</p> Signup and view all the answers

    Which of the following compounds is commonly conjugated to a drug in Phase II metabolism?

    <p>Glucuronic acid</p> Signup and view all the answers

    Phase II metabolism can occur with or without Phase I. Which of the following functional groups is directly involved in Phase II conjugation?

    <p>Hydroxyl group</p> Signup and view all the answers

    Which phase of drug metabolism is most responsible for converting a drug into a water-soluble form for excretion?

    <p>Phase II</p> Signup and view all the answers

    Which process typically follows Phase I reactions and enhances the drug's excretion?

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

    Which of the following is a primary function of Phase I metabolism?

    <p>To introduce or expose functional groups for Phase II metabolism</p> Signup and view all the answers

    Which of the following functional groups is typically introduced during Phase I reactions?

    <p>-OH</p> Signup and view all the answers

    Phase I reactions include all of the following except:

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

    Which cofactor is commonly involved in the oxidation reactions of Phase I metabolism?

    <p>NADPH (Nicotinamide adenine dinucleotide phosphate)</p> Signup and view all the answers

    What is the role of the mixed function oxidase (MFO) system in Phase I metabolism?

    <p>To oxidize drugs using Cytochrome P450, NADPH, and molecular oxygen</p> Signup and view all the answers

    Which of the following enzymes also participates in the oxidation of drugs besides Cytochrome P450?

    <p>Xanthine oxidase</p> Signup and view all the answers

    Which of the following reactions is NOT part of Phase I metabolism?

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

    What is the key result of Phase I reactions in drug metabolism?

    <p>Creation of a reactive site for Phase II conjugation</p> Signup and view all the answers

    Which enzyme system in Phase I metabolism requires molecular oxygen and NADPH to function?

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

    Which type of reaction is hydroxylation classified as in Phase I metabolism?

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

    Which of the following enzymes catalyzes the hydroxylation reaction in Phase I metabolism?

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

    During hydroxylation, what group is introduced into the drug molecule?

    <p>-OH</p> Signup and view all the answers

    Which cofactor is required for the Cytochrome P450-catalyzed hydroxylation of drugs?

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

    What is the role of oxygen (O2) in the hydroxylation reaction catalyzed by Cytochrome P450?

    <p>Provides an oxygen atom for the hydroxyl group</p> Signup and view all the answers

    Which of the following drugs undergoes hydroxylation as a part of its metabolism?

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

    In the metabolism of lidocaine, what is the significance of hydroxylation as the first step?

    <p>It makes the drug more susceptible to Phase II reactions</p> Signup and view all the answers

    Which organ is primarily responsible for the hydroxylation of lidocaine during its metabolism?

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

    Which enzyme catalyzes the first step of ethanol metabolism, converting ethanol to acetaldehyde (ethanal)?

    <p>Alcohol dehydrogenase (ADH)</p> Signup and view all the answers

    What is the product formed during the first stage of ethanol metabolism?

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

    In the second stage of ethanol metabolism, acetaldehyde is further oxidized to which compound?

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

    Which enzyme is responsible for converting acetaldehyde to acetate in the mitochondria?

    <p>Aldehyde dehydrogenase (ALDH)</p> Signup and view all the answers

    Which cofactor is involved in the dehydrogenation reactions during ethanol metabolism?

    <p>NAD+</p> Signup and view all the answers

    Which of the following statements best describes dehydrogenation in the context of ethanol metabolism?

    <p>Removal of two hydrogens from ethanol</p> Signup and view all the answers

    In which cellular organelle does the oxidation of acetaldehyde to acetate primarily occur?

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

    What is the significance of NAD+ in the dehydrogenation of ethanol?

    <p>Accepts electrons and becomes reduced to NADH</p> Signup and view all the answers

    What is the primary purpose of the two-stage ethanol metabolism process?

    <p>To detoxify ethanol by converting it into water-soluble metabolites</p> Signup and view all the answers

    Which of the following organs plays the primary role in ethanol metabolism?

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

    What is the primary mechanism of action of disulfiram in treating alcohol abuse?

    <p>It inhibits the oxidation of acetaldehyde by aldehyde dehydrogenase (ALDH)</p> Signup and view all the answers

    What unpleasant effect is caused by the increased concentration of acetaldehyde due to disulfiram?

    <p>Hangover-like symptoms</p> Signup and view all the answers

    Disulfiram competes with which cofactor for binding sites on aldehyde dehydrogenase (ALDH)?

    <p>NAD+</p> Signup and view all the answers

    What is the approximate increase in acetaldehyde concentration when a person takes disulfiram and consumes alcohol?

    <p>5- to 10-fold</p> Signup and view all the answers

    Why does disulfiram help in maintaining abstinence from alcohol?

    <p>It causes unpleasant side effects when alcohol is consumed</p> Signup and view all the answers

    Disulfiram is highly lipid soluble and accumulates in which type of tissue?

    <p>Adipose tissue</p> Signup and view all the answers

    What is the bioavailability of disulfiram after an oral dose?

    <p>80%</p> Signup and view all the answers

    Which of the following is NOT a result of disulfiram’s inhibition of aldehyde dehydrogenase?

    <p>Faster metabolism of ethanol</p> Signup and view all the answers

    What percentage of codeine is metabolized into morphine?

    <p>10%</p> Signup and view all the answers

    The analgesic effect of codeine is due to its conversion to which metabolite?

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

    What type of reaction is responsible for converting codeine to morphine?

    <p>Oxidative dealkylation</p> Signup and view all the answers

    In the oxidative dealkylation of codeine, what functional group is removed during the reaction?

    <p>Methyl group (-CH3)</p> Signup and view all the answers

    In the metabolism of codeine, the methyl group is oxidized into which compound?

    <p>Methanal (formaldehyde)</p> Signup and view all the answers

    Oxidative dealkylation implies the removal of an alkyl group and its conversion to which type of compound?

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

    Which of the following statements is true about the metabolic conversion of codeine?

    <p>Codeine is a pro-drug that exerts its effects after conversion to morphine</p> Signup and view all the answers

    In the oxidative dealkylation reaction, what happens to the analgesic potency of codeine after conversion to morphine? A) It decreases B) It remains the same C) It increases D) It is lost completely

    <p>It increases</p> Signup and view all the answers

    Which phase I metabolic process is involved in the conversion of codeine to morphine?

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

    What type of drug is chloramphenicol?

    <p>Broad-spectrum antibiotic</p> Signup and view all the answers

    In the context of reduction reactions, what does the term "reduction" imply?

    <p>Addition of two hydrogens</p> Signup and view all the answers

    What functional group is represented by the term "nitro" in chloramphenicol?

    <p>-NO2</p> Signup and view all the answers

    Which of the following statements is true regarding the reduction of chloramphenicol?

    <p>It involves the conversion of the nitro group to an amino group.</p> Signup and view all the answers

    During the reduction of chloramphenicol, which of the following occurs?

    <p>The nitro group is reduced to an amine.</p> Signup and view all the answers

    What is the primary metabolic pathway for chloramphenicol?

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

    Which of the following enzymes is commonly involved in the reduction of nitro compounds like chloramphenicol?

    <p>Nitro-reductase</p> Signup and view all the answers

    What happens to chloramphenicol after it undergoes reduction?

    <p>It is converted to an inactive metabolite.</p> Signup and view all the answers

    What is the significance of the reduction of chloramphenicol in clinical use?

    <p>It helps in the detoxification of the drug.</p> Signup and view all the answers

    Which of the following best describes the role of nitro groups in chloramphenicol?

    <p>They serve as a site for reduction reactions.</p> Signup and view all the answers

    What type of drug is procaine?

    <p>Local anesthetic</p> Signup and view all the answers

    What is the effect of hydrolysis on procaine?

    <p>It inactivates the drug.</p> Signup and view all the answers

    During the hydrolysis of aspirin, which two products are formed?

    <p>Salicylic acid and acetic acid</p> Signup and view all the answers

    What does hydrolysis imply in the context of drug metabolism?

    <p>Addition of water</p> Signup and view all the answers

    At what pH does aspirin hydrolyze to salicylate and acetate?

    <p>pH 7</p> Signup and view all the answers

    Which of the following enzymes is primarily responsible for the hydrolysis of procaine?

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

    What is the main purpose of hydrolysis in drug metabolism?

    <p>To inactivate drugs and prepare them for excretion</p> Signup and view all the answers

    What is a key characteristic of the hydrolysis reaction involving procaine?

    <p>It results in the formation of para-aminobenzoic acid (PABA).</p> Signup and view all the answers

    In the context of aspirin hydrolysis, what is the role of salicylic acid? A) It is an active metabolite with anti-inflammatory properties. B) It is an inactive metabolite. C) It acts as a pro-drug. D) It enhances the absorption of aspirin.

    <p>It is an active metabolite with anti-inflammatory properties.</p> Signup and view all the answers

    Which of the following best describes the overall process of hydrolysis? a) It increases molecular weight. b) It leads to the formation of smaller, more water-soluble molecules. c) It is a non-reversible reaction. d) It requires enzyme catalysis to proceed.

    <p>It leads to the formation of smaller, more water-soluble molecules.</p> Signup and view all the answers

    What is the primary goal of Phase II metabolism?

    <p>To conjugate hydrophilic groups with functional groups</p> Signup and view all the answers

    Which of the following is NOT a primary conjugation reaction in Phase II metabolism?

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

    What type of enzyme primarily catalyzes the conjugation reactions in Phase II metabolism?

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

    Which functional groups can be involved in glucuronic acid conjugation?

    <p>All of the above</p> Signup and view all the answers

    In sulfate conjugation, which functional groups are primarily targeted?

    <p>-NH2 and -OH groups</p> Signup and view all the answers

    Glycine conjugation primarily occurs on which functional group?

    <p>-COOH groups</p> Signup and view all the answers

    What type of compounds can undergo glutathione conjugation?

    <p>Electrophilic compounds, epoxides, and organic halides</p> Signup and view all the answers

    What is the outcome of Phase II metabolism in terms of drug excretion?

    <p>Production of water-soluble products that can be excreted in bile or urine</p> Signup and view all the answers

    What role do coenzymes play in Phase II metabolism?

    <p>They assist transferase enzymes in the conjugation process.</p> Signup and view all the answers

    Which of the following statements about Phase II metabolism is true? a) It primarily occurs in the kidneys. b) It results in the formation of less water-soluble metabolites. c) It makes drugs more easily excreted from the body. d) It is solely dependent on cytochrome P450 enzymes.

    <p>It makes drugs more easily excreted from the body.</p> Signup and view all the answers

    What is the role of uridine diphosphate glucuronic acid (UDP-GA) in glucuronidation?

    <p>It acts as a substrate for the enzyme.</p> Signup and view all the answers

    Which enzyme is primarily responsible for the transfer of glucuronic acid to the drug during glucuronidation?

    <p>Glucuronyl transferase</p> Signup and view all the answers

    Which of the following is true about glucuronic acid (C6H10O7)?

    <p>It is a carbohydrate derivative.</p> Signup and view all the answers

    In glucuronidation, which type of functional group is often represented as RO-GA?

    <p>Hydroxyl or carboxyl groups</p> Signup and view all the answers

    What happens to the polarity of a drug after undergoing glucuronidation? a) It becomes less polar. b) It remains unchanged. c) It becomes more polar. d) It becomes lipophilic.

    <p>It becomes more polar.</p> Signup and view all the answers

    Which statement accurately describes the glucuronidation process?

    <p>It requires the presence of UDP-GA and glucuronyl transferase.</p> Signup and view all the answers

    What type of functional group is primarily involved in sulfation?

    <p>Phenolic groups</p> Signup and view all the answers

    What is the role of 3-phosphoadenosine-5'-phosphosulfate (PAPS) in the sulfation process?

    <p>It serves as a substrate for sulfate transfer.</p> Signup and view all the answers

    Which enzyme is primarily responsible for the transfer of sulfate to the drug during sulfation?

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

    Which of the following compounds can undergo both glucuronidation and sulfation?

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

    Which of the following statements is true about sulfation?

    <p>It often competes with glucuronidation for the same substrates.</p> Signup and view all the answers

    What type of reaction does sulfation represent in drug metabolism?

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

    Which functional group is commonly transferred to a drug during sulfation?

    <p>Sulfate group</p> Signup and view all the answers

    What effect does sulfation typically have on the pharmacological activity of a drug?

    <p>It reduces or terminates activity.</p> Signup and view all the answers

    Which of the following compounds is commonly conjugated with glycine?

    <p>Benzoic acid</p> Signup and view all the answers

    What is the primary function of glycine conjugation in drug metabolism?

    <p>To facilitate excretion of metabolites</p> Signup and view all the answers

    Glycine conjugation primarily occurs with which type of functional group?

    <p>Carboxyl groups</p> Signup and view all the answers

    Which enzyme is involved in the conjugation of drugs with glycine?

    <p>Glycine transferase</p> Signup and view all the answers

    Which of the following is a characteristic of glycine conjugation?

    <p>It involves the formation of glycine-derived metabolites.</p> Signup and view all the answers

    At low doses of aspirin, what is the main metabolic pathway?

    <p>Ester hydrolysis</p> Signup and view all the answers

    At low doses of aspirin, what is the main metabolic pathway?

    <p>Glycine conjugation</p> Signup and view all the answers

    At higher doses of aspirin, which metabolic pathway becomes saturated?

    <p>Glycine conjugation</p> Signup and view all the answers

    What is the main metabolite of aspirin after hydrolysis at pH ~7?

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

    After the saturation of glycine conjugation pathways at higher doses, which conjugation pathway becomes significant?

    <p>Glucuronic acid conjugation</p> Signup and view all the answers

    Which statement is true regarding the metabolism of aspirin at high doses? a) Glycine conjugation remains the primary pathway. b) Glucuronic acid conjugation becomes significant after glycine saturation. c) Hydrolysis is the main route of metabolism at all doses. d) Aspirin is primarily excreted unchanged.

    <p>Glucuronic acid conjugation becomes significant after glycine saturation.</p> Signup and view all the answers

    What happens to the glucuronic acid conjugation pathway at high doses of aspirin?

    <p>It becomes saturated, leading to direct urinary excretion.</p> Signup and view all the answers

    What are the two main Phase II metabolic pathways for paracetamol?

    <p>Glucuronidation and sulfation</p> Signup and view all the answers

    What percentage of paracetamol is typically excreted via glucuronidation?

    <p>45-50%</p> Signup and view all the answers

    What is the minor Phase I metabolic pathway of paracetamol?

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

    What toxic compound is formed during the Phase I metabolism of paracetamol?

    <p>N-Acetyl-p-benzoquinone imine (NAPQI)</p> Signup and view all the answers

    What happens to NAPQI at low doses of paracetamol (1-2 g)?

    <p>It conjugates with glutathione (GSH) and is excreted.</p> Signup and view all the answers

    Which enzyme is responsible for the conjugation of NAPQI with glutathione?

    <p>Glutathione transferase</p> Signup and view all the answers

    What is the primary role of glutathione (GSH) in the metabolism of paracetamol?

    <p>To conjugate with toxic electrophiles</p> Signup and view all the answers

    What percentage of paracetamol is typically metabolized through the minor Phase I pathway?

    <p>4-5%</p> Signup and view all the answers

    What is the function of the reactive thiol group (SH) in glutathione?

    <p>It reacts with harmful electrophiles produced during metabolism.</p> Signup and view all the answers

    What toxic compound increases in amounts when the glutathione pathway becomes saturated at high doses of paracetamol?

    <p>N-Acetyl-p-benzoquinone imine (NAPQI)</p> Signup and view all the answers

    What is the potential consequence of elevated NAPQI levels in the liver?

    <p>Attack on liver cells, which can be fatal</p> Signup and view all the answers

    What does SG stand for in the context of glutathione?

    <p>Sulfur (S) of glutathione and G for the rest of glutathione</p> Signup and view all the answers

    What role does the P450 system play in the metabolism of paracetamol?

    <p>It produces toxic metabolites like NAPQI.</p> Signup and view all the answers

    What is the primary purpose of using prodrugs in pharmacology?

    <p>To modify undesirable properties of a drug.</p> Signup and view all the answers

    Which of the following is a reason for using a prodrug to achieve site-specific drug delivery?

    <p>To allow the active drug to accumulate in the target cells.</p> Signup and view all the answers

    How do prodrugs assist in overcoming drug instability?

    <p>By forming derivatives that are less reactive.</p> Signup and view all the answers

    Which prodrug example is specifically cited for delivering morphine across the blood-brain barrier?

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

    What role do acetyl groups play in the effectiveness of the prodrug Diamorphine?

    <p>They enhance the lipophilicity of the drug to aid in membrane crossing.</p> Signup and view all the answers

    In the context of prodrugs, what is meant by 'slow or prolonged release'?

    <p>Controlled release of active agents to sustain dosage over time.</p> Signup and view all the answers

    Prodrugs can mask toxicity or side effects of certain drugs. Which scenario exemplifies this usage?

    <p>Using anticancer agents that target only tumor cells.</p> Signup and view all the answers

    What benefit do prodrugs offer in the context of absorption across cell membranes?

    <p>Alter lipophilicity to aid in membrane penetration.</p> Signup and view all the answers

    Which of the following describes a potential disadvantage of not using a prodrug?

    <p>Increased risk of side effects from the drug.</p> Signup and view all the answers

    What is the primary role of the prodrug Enalapril in the treatment of hypertension?

    <p>To enhance patient compliance through prolonged drug release</p> Signup and view all the answers

    Which enzyme is primarily responsible for metabolizing Enalapril into its active form?

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

    Which of the following best describes the pharmacokinetics of Haloperidol decanoate?

    <p>Intramuscular injection with prolonged antipsychotic activity</p> Signup and view all the answers

    Why are prodrugs particularly advantageous in the treatment of psychosis?

    <p>They simplify dosing regimens for patients.</p> Signup and view all the answers

    What characteristic is shared by both Enalapril and Haloperidol decanoate?

    <p>Both undergo metabolism to become effective drugs.</p> Signup and view all the answers

    What is a common challenge associated with the bitter taste of Sulfisoxazole?

    <p>It may lead to poor patient compliance.</p> Signup and view all the answers

    How does the use of prodrugs impact patient compliance in chronic illness management?

    <p>They offer extended release formulations that reduce the need for frequent dosing.</p> Signup and view all the answers

    What time frame is observed for peak plasma levels after administering Enalapril?

    <p>2-6 hours after administration</p> Signup and view all the answers

    Which of the following best encapsulates the function of esterases in the context of prodrugs?

    <p>They convert prodrugs to their pharmacologically active counterparts.</p> Signup and view all the answers

    What is the primary condition that Haloperidol decanoate addresses?

    <p>Psychotic disorders, including schizophrenia</p> Signup and view all the answers

    What is the main purpose of using prodrugs in pharmacology?

    <p>To enhance the stability and delivery of the active drug</p> Signup and view all the answers

    Which issue related to drug administration can the use of prodrugs specifically address?

    <p>Overcoming instability and improving absorption</p> Signup and view all the answers

    How do prodrugs facilitate site-specific drug delivery?

    <p>By masking the drug until it reaches the target site</p> Signup and view all the answers

    What metabolic process converts the prodrug diamorphine back to its active form, morphine?

    <p>Ester hydrolysis</p> Signup and view all the answers

    What is a key characteristic of prodrugs in relation to their pharmacological activity?

    <p>They are initially inactive until metabolized</p> Signup and view all the answers

    Why might a drug with high polarity benefit from being developed as a prodrug?

    <p>To facilitate crossing hydrophobic cell membranes</p> Signup and view all the answers

    What advantage does a prodrug provide concerning drug release duration?

    <p>Controlled, prolonged release of the active agent</p> Signup and view all the answers

    In the context of patient compliance, what aspect of prodrugs can be particularly beneficial?

    <p>They mask unpleasant drug properties</p> Signup and view all the answers

    Which characteristic of diamorphine allows it to cross the blood-brain barrier more effectively than morphine?

    <p>Acetylation of the -OH groups</p> Signup and view all the answers

    What role do esterases play in the metabolism of Enalapril?

    <p>They convert it to the active form, Enalaprilat.</p> Signup and view all the answers

    Why is Haloperidol decanoate considered a pro-drug?

    <p>It requires metabolization for its antipsychotic effects.</p> Signup and view all the answers

    What is the primary benefit of using pro-drugs like Haloperidol decanoate in treating psychoses?

    <p>They increase patient compliance by reducing administration frequency.</p> Signup and view all the answers

    Which drug is an example of a tasteless antibiotic pro-drug?

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

    What is the duration of the antipsychotic activity of Haloperidol decanoate after administration?

    <p>1 month</p> Signup and view all the answers

    In the context of pro-drugs, what is a critical factor for their successful use?

    <p>Slow conversion to the active drug.</p> Signup and view all the answers

    How does the polarity of Enalapril compare to Enalaprilat?

    <p>Enalapril is less polar than Enalaprilat.</p> Signup and view all the answers

    What therapeutic conditions are treated with ACE inhibitors like Enalapril?

    <p>Hypertension and congestive heart failure.</p> Signup and view all the answers

    Which of the following statements about the administration of Haloperidol decanoate is true?

    <p>It is injected intramuscularly.</p> Signup and view all the answers

    What characteristic of Sulfisoxazole makes it more acceptable for patients?

    <p>It is tasteless.</p> Signup and view all the answers

    Study Notes

    Drug Metabolism

    • Drug metabolism is the process of transforming drugs in the body using enzymes.
    • Metabolites are the products of these transformations.
    • The goal of metabolism is to convert lipophilic (fat-soluble) drugs into hydrophilic (water-soluble) metabolites so they can be excreted.
    • Metabolism increases renal excretion and decreases tubular re-absorption.

    Consequences of Drug Metabolism

    • Drugs can be converted into excretable forms.
    • Drug action can be terminated.
    • Drugs can be converted into metabolites with pharmacological activity.
    • Inactive compounds called pro-drugs can be converted into active metabolites.

    Where Drug Metabolism Happens

    • The liver is the primary organ for drug metabolism.
    • Other active tissues include the gastrointestinal tract, lungs, skin, and kidneys.
    • Liver cells contain efficient enzymes for metabolizing foreign substances.

    Phase I Metabolism

    • Introduction: Phase I metabolism transforms a drug into a more polar metabolite by introducing a functional group (e.g., via oxidation, reduction, or hydrolysis).
    • Oxidation Reactions: Often catalyzed by cytochrome P450 enzymes, primarily located in the endoplasmic reticulum of hepatocytes.
    • Other Enzymes: Other enzymes in the body also oxidize drugs (example: xanthine oxidase, amine oxidases).

    Phase I Oxidation Reactions – Oxidation / Hydroxylation

    • Hydroxylation: Addition of an -OH group (a type of oxidation).
    • Example — Lidocaine: Lidocaine metabolism begins with hydroxylation.

    Phase I Oxidation Reactions – Oxidation / Dehydrogenation

    • Dehydrogenation: Removal of two hydrogens from a molecule.
    • Example — Ethanol: Most ethanol metabolism occurs in the liver. Ethanol is oxidized to ethanal (acetaldehyde) by alcohol dehydrogenase (ADH), then to acetate by aldehyde dehydrogenase (ALDH).

    Disulfiram (Antabuse) — Treatment of Alcohol Abuse

    • Mechanism: Disulfiram irreversibly inhibits ALDH by competing with the cofactor NAD+ for binding sites.
    • Consequences: Increased acetaldehyde levels cause unpleasant side effects (hangover-like).

    Phase I Oxidation Reactions – Dealkylation

    • Dealkylation: Removal of an alkyl group (typically methyl).
    • Example — Codeine: Codeine is converted to morphine by oxidative dealkylation, responsible for its analgesic effect.

    Phase I Reactions – Reduction

    • Reduction: Addition of two hydrogens to a molecule.
    • Example — Chloramphenicol: A broad-spectrum antibiotic undergoes reduction.

    Phase I Reactions – Hydrolysis

    • Hydrolysis: Addition of water (H2O) to a molecule, breaking it into two parts.
    • Examples: Aspirin hydrolysis at pH ~ 7, Procaine (local anesthetic) hydrolysis.

    Phase I Summary

    • Phase I reactions prepare drugs for Phase II metabolism and excretion.
    • Phase II is the true "detoxification" step.

    Phase II Metabolism

    • Conjugation Reactions: Glucuronic acid conjugation, Sulfate conjugation, Glycine conjugation, Glutathione conjugation.
    • Catalysts: Transferase enzymes and various coenzymes.
    • Mechanism: Conjugation involves attaching a hydrophilic group to a functional group already present in the molecule (potentially from Phase I), making the product water-soluble for excretion in bile or urine.

    Glucuronic Acid Conjugation

    • Transfer: Glucuronic acid is transferred from uridine diphosphate glucuronic acid (UDP-GA) to the drug by glucuronyl transferase.
    • Importance: Most common conjugation type, forming glucuronides (quantitatively the most important Phase II pathway).
    • Common Drugs: Drugs with -OH, -COOH, -NH2 groups.

    Sulfate Conjugation (Sulfation)

    • Common for: Phenols (aromatic alcohols).
    • Transfer: Sulfate is transferred from 3-phosphoadenosine-5'-phosphosulfate (PAPS) to the drug by sulfotransferase.
    • Competition: Glucuronide formation and sulfation often compete for the same substrate (e.g., paracetamol).

    Glycine Conjugation

    • Transfer: Glycine is conjugated to -COOH groups.

    Metabolism of Aspirin

    • Low doses: Aspirin is primarily metabolized by glycine conjugation.
    • Higher doses: Glycine conjugation pathway becomes saturated, and glucuronide conjugation predominates.
    • Top doses: Saturation of conjugation pathways leads to direct urinary excretion of aspirin.

    Paracetamol and its Metabolism

    • Properties: Analgesic, antipyretic, but weak anti-inflammatory.

    Paracetamol — Two Main Phase II Metabolic Pathways

    • Glucuronidation: 45-50% of paracetamol is metabolized via glucuronidation.
    • Sulfation: 45-50% of paracetamol is metabolized via sulfation.

    Paracetamol — Another Minor Phase I Metabolic Pathway

    • Oxidation: Paracetamol is oxidized by the P450 system to N-Acetyl-p-benzoquinone imine (NAPQI), which is toxic to the liver.
    • Glutathione Conjugation: At low doses, NAPQI conjugates with glutathione (GSH) and is excreted.

    Glutathione (GSH)

    • Function: Reacts with harmful electrophiles produced during metabolism.

    Paracetamol — Fatal at High Doses

    • High doses: Saturation of glutathione pathway allows NAPQI buildup, damaging liver cells and causing fatal liver failure.

    Prodrugs

    • A prodrug is a pharmacologically inactive compound that is transformed into an active drug within the body.
    • Prodrugs are used to overcome various challenges related to drug properties and delivery.
    • Examples of prodrug uses:
      • Overcoming drug instability: Convert unstable drugs into stable derivatives that are activated in the body.
      • Site-specific drug delivery: Alter drug properties to enable delivery to specific target sites within the body.
      • Improving physicochemical properties: Adjust drug polarity, solubility, or other properties for better absorption, formulation, or distribution.
      • Slow/prolonged release: Create formulations that release the active drug slowly over time, allowing for controlled dosage and extended therapeutic effects.
      • Masking drug toxicity or side effects: Minimize harmful effects by targeting drug activity to specific cells or tissues.
      • Masking unpleasant properties: Enhance patient compliance by improving drug taste, smell, or other sensory characteristics.

    Diamorphine: Prodrug for Site-Specific Delivery

    • Diamorphine (heroin) is a prodrug of morphine, used to deliver morphine to the central nervous system.
    • Diamorphine is more lipophilic than morphine, allowing it to cross the blood-brain barrier more easily.
    • Once in the brain, enzymes called esterases remove the acetyl groups from diamorphine, converting it into morphine.

    Enalapril: Prodrug for Physicochemical Property Improvement

    • Enalaprilat is an angiotensin-converting-enzyme (ACE) inhibitor, but its polarity makes it poorly absorbed.
    • Enalapril, the prodrug of Enalaprilat, is less polar and better absorbed.
    • Enalapril is metabolized by esterases in the body to the active drug Enalaprilat.

    Haloperidol Decanoate: Prodrug for Slow and Prolonged Drug Release

    • Haloperidol decanoate is a prodrug of haloperidol, an antipsychotic medication.
    • Haloperidol decanoate is injected intramuscularly.
    • The slow conversion to haloperidol provides prolonged antipsychotic activity, lasting for about a month.

    Sulfisoxazole Acetyl: Prodrug to Encourage Patient Acceptance

    • Sulfisoxazole is an antibacterial sulfa drug, but it has a bitter taste.
    • Sulfisoxazole acetyl is a prodrug of sulfisoxazole that is tasteless.
    • This improves patient compliance by making the medication more palatable.

    Pro-drugs

    • A prodrug is a pharmacologically inactive precursor to an active drug
    • Prodrugs undergo biotransformation before exhibiting their pharmacological effects
    • They can be viewed as drugs containing protective groups, transiently altering or eliminating undesirable properties in the parent molecule

    Why & When are Prodrugs Used

    • Overcoming drug instability: Unstable drugs are converted into stable derivatives in vivo
    • Site-specific drug delivery: Drugs that cannot reach the target site are converted into derivatives that can, at the target site
    • Improvement of physicochemical properties:
      • Absorption: drugs may be too polar (not cross membranes) or too non-polar (not exit membrane)
      • Solubility: Increasing or decreasing solubility can achieve desired formulation
    • Slow/prolonged release of the active agent: Controlled release allows maintenance of an effective drug dosage
    • Masking drug toxicity or side effects: Prodrugs preferentially accumulate in tumors, reducing unwanted toxicity
    • Masking unpleasant properties: Encourages patient compliance

    Pro-drugs for Site Specific Drug Delivery

    • Diamorphine (heroin) is a pro-drug that delivers morphine to the central nervous system
    • Morphine’s –OH groups are acetylated in diamorphine, making it more lipophilic and allowing it to cross the blood-brain barrier
    • Acetyl groups are removed by esterases, yielding morphine

    Pro-drugs for Improvement of Physicochemical Properties

    • Enalaprilat (ACE inhibitor) is poorly absorbed due to its polarity
    • Enalapril (prodrug) is less polar and better absorbed
    • Enalapril is metabolized by esterases to the active drug Enalaprilat
    • Note: ACE inhibitor = angiotensin-converting-enzyme inhibitor (used for hypertension and congestive heart failure)

    Pro-drugs for Slow and Prolonged Drug Release

    • Haloperidol is a depressant, sedative, and tranquilizer used to treat psychotic disorders
    • Peak plasma levels occur 2-6 hours after administration
    • Haloperidol decanoate is an ester pro-drug that, when injected intramuscularly, slowly converts to haloperidol for an antipsychotic effect lasting 1 month
    • This use of pro-drugs is important in the treatment of psychoses where long-term medication is required and patient non-compliance is high

    Pro-drugs to Encourage Patient Acceptance

    • Sulfisoxazole is an antibacterial sulfa drug, but is bitter tasting
    • Sulfisoxazole acetyl is a tasteless prodrug

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    Description

    This quiz delves into the essential concepts of drug metabolism, exploring how the body transforms drugs into metabolites, the organs involved, and the phases of metabolism. Understanding these processes is crucial for comprehending drug action and pharmacology. Test your knowledge and grasp of these fundamental topics in drug metabolism.

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