Podcast
Questions and Answers
What is an advantage of using methadone as a substitute for morphine or heroin?
What is an advantage of using methadone as a substitute for morphine or heroin?
How does the R form of methadone compare to morphine in terms of activity?
How does the R form of methadone compare to morphine in terms of activity?
What strategy involves removing ring B, C, D, and E from morphine?
What strategy involves removing ring B, C, D, and E from morphine?
Which of the following is a property of buprenorphine compared to morphine?
Which of the following is a property of buprenorphine compared to morphine?
Signup and view all the answers
Why is sublingual administration preferred for buprenorphine over oral administration?
Why is sublingual administration preferred for buprenorphine over oral administration?
Signup and view all the answers
What does the Greek word 'opium' mean?
What does the Greek word 'opium' mean?
Signup and view all the answers
What is the correct year in which morphine was first isolated?
What is the correct year in which morphine was first isolated?
Signup and view all the answers
Which of the following analogues has rings C & D removed?
Which of the following analogues has rings C & D removed?
Signup and view all the answers
Which of the following is NOT a side effect of morphine?
Which of the following is NOT a side effect of morphine?
Signup and view all the answers
What is the recommended reading for Lectures 4&5 on Opioid Analgesics?
What is the recommended reading for Lectures 4&5 on Opioid Analgesics?
Signup and view all the answers
What was the first method used to determine the structure of morphine in 1968?
What was the first method used to determine the structure of morphine in 1968?
Signup and view all the answers
What is the primary application of drug design strategies discussed in Lectures 4&5?
What is the primary application of drug design strategies discussed in Lectures 4&5?
Signup and view all the answers
In opioid analgesics, what is the substance extracted from the poppy seeds called?
In opioid analgesics, what is the substance extracted from the poppy seeds called?
Signup and view all the answers
Which compound is used to counter addiction to more potent opioids like heroin?
Which compound is used to counter addiction to more potent opioids like heroin?
Signup and view all the answers
Which of the following is NOT a method for simplification of opioid analogues?
Which of the following is NOT a method for simplification of opioid analogues?
Signup and view all the answers
What is the primary difference between opiates and opioids?
What is the primary difference between opiates and opioids?
Signup and view all the answers
What is the main purpose of using opioid analgesics as an inducing agent with general anesthetics?
What is the main purpose of using opioid analgesics as an inducing agent with general anesthetics?
Signup and view all the answers
What is the simplified analogue that is mentioned as 20% the activity of morphine?
What is the simplified analogue that is mentioned as 20% the activity of morphine?
Signup and view all the answers
Which compound is identified as an antagonist and 5 times more potent than morphine?
Which compound is identified as an antagonist and 5 times more potent than morphine?
Signup and view all the answers
What is the name of the compound that is 15 times more potent than morphine?
What is the name of the compound that is 15 times more potent than morphine?
Signup and view all the answers
Which substance shares the same analgesic activity as morphine after removing rings C and D?
Which substance shares the same analgesic activity as morphine after removing rings C and D?
Signup and view all the answers
What compound is mentioned as 4 times more active than morphine but lacks dependence properties?
What compound is mentioned as 4 times more active than morphine but lacks dependence properties?
Signup and view all the answers
Which drug has very low risk of addiction and does not depress breathing?
Which drug has very low risk of addiction and does not depress breathing?
Signup and view all the answers
Which compound has less severe emetic and constipation effects compared to others mentioned?
Which compound has less severe emetic and constipation effects compared to others mentioned?
Signup and view all the answers
What compound is useful for long-term analgesia and has a rapid onset and short duration?
What compound is useful for long-term analgesia and has a rapid onset and short duration?
Signup and view all the answers
Which benzomorphan is stated to have the same potency as morphine when ring C and D are removed?
Which benzomorphan is stated to have the same potency as morphine when ring C and D are removed?
Signup and view all the answers
Which compound led to the development of a drug with 200 times the activity of morphine and no addictive properties?
Which compound led to the development of a drug with 200 times the activity of morphine and no addictive properties?
Signup and view all the answers
What is the main receptor of morphine responsible for its analgesic effect?
What is the main receptor of morphine responsible for its analgesic effect?
Signup and view all the answers
Which modification in morphine analogues retained their activity according to the SAR analysis?
Which modification in morphine analogues retained their activity according to the SAR analysis?
Signup and view all the answers
How many chiral centers are present in morphine?
How many chiral centers are present in morphine?
Signup and view all the answers
What functional group in morphine is identified as crucial for its analgesic activity?
What functional group in morphine is identified as crucial for its analgesic activity?
Signup and view all the answers
Which drug extension strategy involves adding extra functional groups to probe for extra binding regions?
Which drug extension strategy involves adding extra functional groups to probe for extra binding regions?
Signup and view all the answers
What is the effect of increasing the size of the alkyl group attached to the nitrogen in morphine?
What is the effect of increasing the size of the alkyl group attached to the nitrogen in morphine?
Signup and view all the answers
Which compound has some agonist activity along with antagonistic properties among naloxone, naltrexone, and nalorphine?
Which compound has some agonist activity along with antagonistic properties among naloxone, naltrexone, and nalorphine?
Signup and view all the answers
What is the effect of introducing a C-14 hydroxyl group on oxymorphone and oxycodone according to SAR analysis?
What is the effect of introducing a C-14 hydroxyl group on oxymorphone and oxycodone according to SAR analysis?
Signup and view all the answers
What is the bioactive enantiomer of morphine based on its stereochemistry?
What is the bioactive enantiomer of morphine based on its stereochemistry?
Signup and view all the answers
What happens when an aromatic ring is added to a morphine analogue?
What happens when an aromatic ring is added to a morphine analogue?
Signup and view all the answers
Study Notes
Opioid Analgesics
- Opium is a Greek word meaning "juice" or extract of seeds from the poppy Papaver somniferum.
- Morphine is the active principle of opium, which contains over 20 different alkaloids.
- Opioid analgesics are drugs that can relieve pain without causing narcosis (loss of consciousness).
Morphine
- First isolated in 1804 and its correct structure was proposed in 1925.
- Morphine is a T-Shaped molecule with functional groups capable of forming ionic, hydrogen bond, and van der Waals interactions.
- Carbon skeleton is capable of forming van der Waals interactions.
- Mask or remove a functional group to test the analogue for activity and determine the importance of a functional group for activity.
Structure Activity Relationships (SAR)
- Increasing hydrophobicity by adding extra carbons can increase activity.
- Masking polar functional groups can increase activity.
- Correct balance between hydrophobic and polar factors is required for water solubility, fat solubility, oral absorption, and ability to cross the blood-brain barrier.
Heroin
- First synthesised in 1898 and is 2-3 times more potent than morphine.
- Crosses the blood-brain barrier and is metabolised in the liver to morphine.
- Has a stronger analgesic effect than morphine but also has stronger side effects.
Simplification Strategies
- Removing non-essential functional groups, excess rings, and excess asymmetric centres can give rise to simpler analogues with increased activity.
- Simplification can lead to easier and cheaper synthesis, but may also increase or decrease side effects.
Morphinans
- Removing the oxygen bridge (ring D) and the hydroxyl and alkene functional groups gives a series of tetracyclic compounds called the morphinans.
- N-methylmorphinan is the simplest of the morphinans and has 20% the activity of morphine.
Benzomorphans
- Removing both rings C and D gives rise to the benzomorphans, which retain analgesic activity.
- The simplest, metazocine, has the same analgesic activity as morphine.
- Replacing the N-methyl group of metazocine with a phenyl group gives phenazocine, which is 4 times more active than morphine.
Pethidine
- Removing ring B gives pethidine, which is useful for child labour and has less severe emetic and constipation effects.
- Generates morphine in the brain, but has less severe withdrawal symptoms.
Buprenorphine
- Has a minimal euphoric effect and less severe withdrawal symptoms.
- Used as a substitute for morphine or heroin to treat addicts.
- Has a flexible molecule with a different binding mode from morphine.
- R form has 2x the activity of morphine, and S form is inactive.
Opioid Receptors
- Morphine has 3 receptors: Mu (µ), Kappa (κ), and Delta (δ).
- Mu is the main receptor for analgesic and side effects.
- Kappa has a weak analgesic effect, and Delta has a weak analgesic effect.
- Drug selectivity for peptide and opioid drugs for receptor subtypes is important.
Aims of Opioid Drug Design
- To maintain activity while lowering side effects.
- To increase oral activity.
- To design agonists with a low risk of addiction and dependence.
Studying That Suits You
Use AI to generate personalized quizzes and flashcards to suit your learning preferences.
Description
Test your knowledge on the opioid analgesics covered in Dr. A. Edwards' Senior Lecturer in Pharmaceutical Chemistry lecture 4&5 at Medway School of Pharmacy. This quiz is based on Chapter 24 of 'The Science of Medicine 3' course and recommended readings like 'An introduction to medicinal chemistry' by Graham Patrick.
