Organic Pharmaceutical Chemistry II
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Organic Pharmaceutical Chemistry II

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Questions and Answers

What is the prototype ligand for the µ-receptor?

  • Morphine (correct)
  • Heroin
  • Codeine
  • Hydromorphone

    • Which structural feature limits morphine's total number of optical isomers?

  • The C-9 to C-13 ethane amino bridge (correct)
  • The esterification of hydroxyl groups
  • The presence of five chiral centers
  • The diacetylation process

    • How is commercial codeine primarily prepared?

  • By dehydrogenation of morphine
  • By acetylation of morphine
  • By oxidation of morphine
  • By methylating the phenolic OH group of morphine (correct)

    • What is one specific side effect of codeine?

    <p>Respiratory depression</p> Signup and view all the answers

    Why does heroin have a quicker effect than morphine?

    <p>It contains two acetyl groups</p> Signup and view all the answers

    What is the primary use of morphine?

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

    What reduces the potency of hydromorphone compared to morphine?

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

    What is a common use for codeine in combination with other medications?

    <p>Treatment of moderate pain</p> Signup and view all the answers

    What is the primary indication for Vivitrol?

    <p>Alcohol dependence</p> Signup and view all the answers

    Which opioid antagonist is primarily used to reverse respiratory depression due to opioid overdose?

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

    What distinguishes methylnaltrexone from other opioid antagonists?

    <p>It only acts as an antagonist at peripheral opioid receptors</p> Signup and view all the answers

    Which statement about nalmefene is true?

    <p>It is a solution for IV, IM, or SC administration</p> Signup and view all the answers

    What is a significant challenge faced in treating opioid dependence therapeutically?

    <p>Poor compliance and high relapse rates among patients</p> Signup and view all the answers

    What is the reason oxymorphone has enhanced potency compared to hydromorphone?

    <p>It contains an additional hydroxyl group that increases receptor affinity.</p> Signup and view all the answers

    Which compound is approximately 4 to 5 times less potent than hydromorphone?

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

    What structural modification leads to the creation of benzomorphans?

    <p>The removal of the C ring from the morphinan structure.</p> Signup and view all the answers

    What is the mechanism of action of pentazocine at the μ-receptor?

    <p>Partial agonist and weak antagonist</p> Signup and view all the answers

    Which compound is known for its ability to treat phantom pain and diabetic neuropathy?

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

    What is the primary reason for the higher percentage of patients experiencing dysphoria with pentazocine compared to morphine?

    <p>It is an agonist at the κ-receptor</p> Signup and view all the answers

    What is the role of the 7,8-dihydro-6-keto C ring in hydrocodone?

    <p>It enhances the brain penetration of the compound.</p> Signup and view all the answers

    What is the main clinical use of meperidine?

    <p>Limited use in patients allergic to morphine-type opioids</p> Signup and view all the answers

    How does oxycodone compare to hydrocodone in terms of receptor affinity?

    <p>It has greater receptor affinity due to the additional functional group.</p> Signup and view all the answers

    What adverse effects can normeperidine cause?

    <p>CNS excitation and seizures</p> Signup and view all the answers

    Which form of levorphanol is specifically referenced as offering greater pain relief?

    <p>Levorotatory form</p> Signup and view all the answers

    How does loperamide act as an antidiarrheal agent?

    <p>Inhibits acetylcholine and prostaglandin release</p> Signup and view all the answers

    Which of the following is marketed as a cough and cold formulation available without a prescription?

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

    What differentiates fentanyl from meperidine in terms of structure?

    <p>Has a 4-aniline substitution</p> Signup and view all the answers

    What is the role of the P-glycoprotein pump (MDR1) in relation to loperamide?

    <p>Pumps it out of the brain</p> Signup and view all the answers

    Why should the use of meperidine be limited?

    <p>It can lead to dangerous CNS effects from its metabolite</p> Signup and view all the answers

    What is the primary reason for the use of fentanyl as an adjunct anesthetic?

    <p>Quick onset and recovery</p> Signup and view all the answers

    Which enantiomer of methadone is primarily responsible for its opioid activity?

    <p>R-enantiomer</p> Signup and view all the answers

    What is a unique feature of the transdermal formulation of fentanyl (Duragesic)?

    <p>Beneficial for chronic pain sufferers</p> Signup and view all the answers

    What mechanism contributes to tramadol's analgesic effects?

    <p>Weak µ-opioid agonism</p> Signup and view all the answers

    What effect does tramadol have on respiratory rate and heart rate at recommended doses?

    <p>Minimal effects</p> Signup and view all the answers

    Which of the following potential adverse effects is associated with methadone use?

    <p>QT interval prolongation</p> Signup and view all the answers

    In which way does the structure of tramadol resemble codeine?

    <p>B, D, and E rings removed</p> Signup and view all the answers

    What key characteristic of fentanyl contributes to its high potency compared to meperidine?

    <p>High lipophilicity</p> Signup and view all the answers

    What is the primary pharmacologic activity of nalbuphine at the μ-receptor?

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

    Which of the following opioid agents has the highest affinity for the μ-receptors?

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

    What is a key clinical use of butorphanol?

    <p>Analgesic for migraine attacks</p> Signup and view all the answers

    What is the oral bioavailability of nalbuphine?

    <p>12%</p> Signup and view all the answers

    Which drug is classified as a mixed μ-agonist/antagonist?

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

    What duration of action can be expected from buprenorphine?

    <p>6-8 hours</p> Signup and view all the answers

    Naltrexone is an antagonist at which type of receptor?

    <p>All opioid receptors</p> Signup and view all the answers

    Which characteristic is true about nalbuphine's usage during labor?

    <p>It is used as the sole opioid agent.</p> Signup and view all the answers

    Study Notes

    Organic Pharmaceutical Chemistry II

    • Topic: Medicinal Chemistry
    • Lecturer: Dr. Ahmed Ali Al-Karmalawy, Associate Professor of Medicinal Chemistry

    Narcotic Analgesic

    • Types of Epoxymorphinans:

      • 4,5-Epoxymorphinans
      • Morphinans
      • Benzomorphans
      • 4-Phenylpiperidines and 4-Anilidopiperidines
      • Diphenylheptanes
      • Miscellaneous

    • Morphine:

      • Prototype ligand for the µ-receptor
      • Contains 5 chiral centers and 16 optical isomers
      • Opium contains over 40 alkaloids, with morphine (8%-17%), codeine (0.7%-5%), thebaine (0.1%-2.5%), papaverine (0.5%-1.5%), and noscapine (1%-10%)
      • Poorly soluble in water, thus sulfate salt is formed for oral, IV, and suppository use.
      • Primary use is analgesia.

    • Codeine:

      • Prepared from morphine by methylating the phenolic OH group.
      • Monoacidic base that forms salts (sulfate and phosphate).
      • Similar to morphine but with lower analgesic potency and addiction potential.
      • Side effects include respiratory depression, miosis, constipation, nausea, itching, dry mouth, and drowsiness.
      • Role as an antitussive agent is questioned.
      • Available in combination with aspirin, ibuprofen, or acetaminophen for moderate pain treatment.

    • Heroin:

      • 3,6 diacetylated form of morphine.
      • Passes through blood-brain barrier quicker than morphine, causing euphoria and addiction.
      • Not available as a prescription drug in the US, but available in some countries for cancer and myocardial infarction pain.

    • Hydromorphone:

      • Synthetic derivative of morphine.
      • Oxidation of the 6-OH group decreases potency.
      • Increasing flexibility of 7,8-double bond results in a compound with slightly enhanced binding.
      • Approximately 5 times more potent than morphine.

    • Oxymorphone:

      • 14 beta-hydroxyl version of hydromorphone
      • Analogous to hydrocodone.
      • Lower oral bioavailability than hydromorphone.
      • Injectable form is more potent.

    • Hydrocodone:

      • 3-methoxy version of hydromorphone.
      • Loss of the 3-OH group results in a weaker opioid (about equal to morphine).
      • Better brain penetration and increased binding to the µ-receptor.
      • Marketed as an antitussive agent.
      • Available in combination with anticholinergic agents and acetaminophen/aspirin.

    • Oxycodone:

      • 14 beta-hydroxyl version of hydrocodone.
      • Synthesized from thebaine. 1.5 times more potent than hydrocodone orally due to increased receptor affinity.
      • Marketed with acetaminophen, aspirin, and ibuprofen.

    Morphinans

    • Morphinans were created by removing the E ring of morphine, to simplify the structure.

    Levorphanol

    • Levorotatory form of methorphan.
    • Approximately 7.5 times more potent orally than morphine.
    • Available as tablet and injection.
    • Alternative for patients without adequate pain relief from morphine.

    Dextromethorphan

    • Dextrorotatory form of levorphanol with a methoxy group on the 3-position.
    • OTC cough and cold formulations.
    • Antagonizes the NMDA receptor.
    • Used to treat phantom pain, diabetic neuropathy, and postoperative acute pain.

    Benzomorphans

    • Removing the C ring of the morphinan structure yields benzomorphans (benzazocines).
    • Pentazocine is the only benzomorphan in clinical use.
    • Racemic mixture; partial agonist at the µ-receptor and agonist at the K-receptor; contributes to dysphoria.

    4-Phenylpiperidines and 4-Anilidopiperidines

    • Removal of the B ring from benzomorphans yields 4-substituted piperidines.
    • Structures are flexible, with the A ring existing in either axial or equatorial position.

    Meperidine

    • Discovered in 1939 during serendipitous screening.
    • Low potency at the opioid receptor, but higher brain penetration.
    • Metabolized to normeperidine, causing potential CNS excitation, including tremors, twitching, and myoclonus.

    Diphenoxylate

    • Weak opioid agonist, combined with atropine (Lomotil).
    • Dissuades abuse and used as an antidiarrheal agent

    Loperamide

    • Acts as an antidiarrheal via direct binding to opiate receptors in the gut wall.
    • Decreases peristalsis and fluid secretion to increase GI transit time and reduce fecal matter volume.
    • Effectively crosses the blood-brain barrier, has no significant CNS opioid effects.
    • Eliminated via P-glycoprotein pump (MDR1).
    • Available as capsule form.

    Fentanyl

    • 4-aniline substituent of meperidine increases potency (approximately 500x stronger).
    • Marketed as an analgesic and adjunct anesthetic.
    • Available in injectable and transdermal formulations (Duragesic).

    SAR studies of 4-Phenylpiperidine Analgesics

    • Propionamide is the optimal chain length.
    • Adding polar groups to the 4-piperidine carbon increases potency (e.g. CH2OCH3, COOCH3).

    Diphenylheptanes (Methadone)

    • Synthetic opioid approved for analgesic therapy and opioid maintenance.
    • Racemic mixture is marketed, but opioid activity resides in the R-enantiomer.
    • 7-50 times more potent than the S-enantiomer.

    Miscellaneous

    • Tramadol:
      • Analgesic agent with several mechanisms of action
      • Weak μ-agonist
      • Minimal effect on respiratory rate, heart rate, blood pressure, or GI transit time.
      • Similar structure to codeine (B, D, and E rings removed)
      • Available as a racemic mixture; (+) enantiomer being much stronger.
    • Codeine, tramadol, and other drugs:
      • Some drugs, like tramadol are metabolised to a more potent version by enzymes (e.g. CYP2D6)
    • Buprenorphine:
      • Semisynthetic opiate derived from thebaine
      • Mixed µ-agonist/antagonist (partial agonist) and weak κ-antagonist.
      • High affinity for µ-receptors and slow dissociation means longer duration (6-8 hours).
      • Primarily used for treatment of opioid dependence, but with lower oral bioavailability due to metabolism in the intestines and liver.
      • Sublingual and transdermal formulations are available outside the US.

    Opioid Antagonists

    • Naltrexone:
      • Pure opioid antagonist with highest affinity at μ-receptor.
      • Orally bioavailable, blocks opiate agonist effects (approximately 24 hours).
      • Developed into extended-release injectable microsphere formulation (Vivitrol) for better compliance with opioid/alcohol dependence treatment.
    • Naloxone:
      • Pure opioid antagonist structurally similar to oxymorphone, but with an allyl group instead of a methyl substituent.
      • Used to reverse respiratory depression effects of opioid overdoses.
    • Nalmefene:
      • 6-methylene analog of naltrexone with similar structural characteristics compared to naloxone.
      • Higher oral bioavailability compared to naltrexone and naloxone.
      • Treatment for pathological gambling and alcohol abuse, available in oral form.
    • Methylnaltrexone:
      • Methylated, quaternary form of naltrexone.
      • Acts as an antagonist on peripheral opioid receptors, preventing drug from crossing the blood-brain barrier (BBB).
      • Approved in 2008 to treat opioid-induced constipation in palliative care patients via SC injection .

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    Narcotic Analgesics - Organic Pharmaceutical Chemistry II - PDF

    Description

    Test your knowledge on narcotic analgesics and their chemistry in Organic Pharmaceutical Chemistry II. This quiz covers the types of epoxymorphinans, the structure and use of morphine, and other relevant medicinal chemistry concepts. Enhance your understanding of drug formulations and pharmacology.

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