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Questions and Answers
What is a major characteristic of heroin compared to morphine?
What is a major characteristic of heroin compared to morphine?
Which derivative of morphine is noted for its increased oral activity?
Which derivative of morphine is noted for its increased oral activity?
Why does heroin have a high abuse potential?
Why does heroin have a high abuse potential?
How do the 3-OCH3 derivatives of morphine compare as antitussive agents?
How do the 3-OCH3 derivatives of morphine compare as antitussive agents?
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What is a characteristic of codeine in comparison to morphine?
What is a characteristic of codeine in comparison to morphine?
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The inclusion of which group into the morphine structure increases its analgesic activity?
The inclusion of which group into the morphine structure increases its analgesic activity?
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What describes the analgesic potency of heroin compared to morphine?
What describes the analgesic potency of heroin compared to morphine?
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What effect does the 3-methoxy derivative of morphine have on side effects?
What effect does the 3-methoxy derivative of morphine have on side effects?
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What is a significant side effect of opioids?
What is a significant side effect of opioids?
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What does tolerance in relation to opioids refer to?
What does tolerance in relation to opioids refer to?
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Which endogenous opioid peptide is mentioned as producing opioid activity?
Which endogenous opioid peptide is mentioned as producing opioid activity?
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What is a consequence of developing dependence on opioids?
What is a consequence of developing dependence on opioids?
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Which of the following best describes morphine?
Which of the following best describes morphine?
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Why was morphine not widely used in medicine before 1853?
Why was morphine not widely used in medicine before 1853?
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What effect does morphine primarily have on pain?
What effect does morphine primarily have on pain?
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What can happen as a result of opioid withdrawal?
What can happen as a result of opioid withdrawal?
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What is the primary receptor that hydromorphone acts upon?
What is the primary receptor that hydromorphone acts upon?
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Which derivative of morphine is hydromorphone a part of?
Which derivative of morphine is hydromorphone a part of?
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What effect does oxycodone exhibit at opioid receptors?
What effect does oxycodone exhibit at opioid receptors?
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What is the main therapeutic use of dextromethorphan?
What is the main therapeutic use of dextromethorphan?
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Which of the following statements about oxycodone is correct?
Which of the following statements about oxycodone is correct?
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What does the 14α-hydroxy group generally do to opioid activity?
What does the 14α-hydroxy group generally do to opioid activity?
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What characteristic does dextromethorphan lack compared to μ-opioid agonists?
What characteristic does dextromethorphan lack compared to μ-opioid agonists?
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What aspect of oxycodone contributes to its better absorption compared to morphine?
What aspect of oxycodone contributes to its better absorption compared to morphine?
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What are the analgesic and antipyretic efficacies of acetaminophen compared to conventional NSAIDs?
What are the analgesic and antipyretic efficacies of acetaminophen compared to conventional NSAIDs?
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Which property distinguishes acetaminophen from NSAIDs?
Which property distinguishes acetaminophen from NSAIDs?
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Which hypothesis suggests that acetaminophen works by depleting glutathione stores?
Which hypothesis suggests that acetaminophen works by depleting glutathione stores?
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What can significantly increase acetaminophen hepatotoxicity?
What can significantly increase acetaminophen hepatotoxicity?
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How is acetaminophen synthesized from p-amino phenol?
How is acetaminophen synthesized from p-amino phenol?
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What is the most common antidote for acetaminophen hepatotoxicity?
What is the most common antidote for acetaminophen hepatotoxicity?
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What is the typical first recommended dose of acetaminophen to avoid hepatotoxicity?
What is the typical first recommended dose of acetaminophen to avoid hepatotoxicity?
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In which demographic can acetaminophen be used safely?
In which demographic can acetaminophen be used safely?
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What is the main effect of levo (-) morphine?
What is the main effect of levo (-) morphine?
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Which of the following statements is true regarding morphine metabolism?
Which of the following statements is true regarding morphine metabolism?
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What is a goal in the design of opioid drug analogues?
What is a goal in the design of opioid drug analogues?
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What is the effect of dextro (+) morphine?
What is the effect of dextro (+) morphine?
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Which modifications to morphine could potentially improve its properties?
Which modifications to morphine could potentially improve its properties?
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Which factor is NOT critical for the analgesic activity of morphine and its analogues?
Which factor is NOT critical for the analgesic activity of morphine and its analogues?
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What is a characteristic of morphine HCl and SO4 salts?
What is a characteristic of morphine HCl and SO4 salts?
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What happens during N-demethylation of morphine?
What happens during N-demethylation of morphine?
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What is the primary mechanism of action of colchicine in treating acute gouty arthritis?
What is the primary mechanism of action of colchicine in treating acute gouty arthritis?
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Which of the following medications is classified as a xanthine oxidase inhibitor?
Which of the following medications is classified as a xanthine oxidase inhibitor?
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What is a common side effect associated with long-term use of colchicine?
What is a common side effect associated with long-term use of colchicine?
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What is the role of uricosuric drugs like Probenecid in treating gout?
What is the role of uricosuric drugs like Probenecid in treating gout?
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Which of the following statements about sulfinpyrazone is true?
Which of the following statements about sulfinpyrazone is true?
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Which class of drugs is primarily used for the management of chronic gout symptoms?
Which class of drugs is primarily used for the management of chronic gout symptoms?
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When is colchicine recommended as a treatment option?
When is colchicine recommended as a treatment option?
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What is the primary purpose of xanthine oxidase inhibitors like allopurinol?
What is the primary purpose of xanthine oxidase inhibitors like allopurinol?
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Study Notes
Opioid Analgesics
- Opioids are centrally acting analgesics that bind to opioid receptors in the central nervous system (CNS) and gastrointestinal tract (GIT).
- Opiates are naturally occurring substances derived from the opium poppy plant (opium), or produced by semi-synthesis from morphine. These include morphine, codeine, and thebaine.
- Opioids include natural, semi-synthetic, fully-synthetic, and endogenous substances that mimic the effects of morphine.
- Examples of opioid types include natural opiates (morphine), semi-synthetic opiates (heroin, codeine), fully-synthetic opioids (meperidine, oxycodone), and endogenous peptides (endorphins, enkephalins).
Opiates vs Opioids
- Opiates are natural substances derived from opium poppy plants.
- Opioids are natural, semi-synthetic, fully-synthetic and endogenous substances that mimic the effects of morphine.
Opioid Receptors
- μ (mu) receptors are primarily located in the brain and spinal cord, and are responsible for central analgesia, constipation, respiratory depression, euphoria, miosis, tolerance, physical dependence, and addiction.
- κ (kappa) receptors are located in the brain and spinal cord and are responsible for peripheral analgesia, sedation, dysphoria, minor respiratory depression, minor miosis, less addiction, stimulation of diuresis, and hallucination.
- δ (delta) receptors are found in the brain and are responsible for spinal analgesia, antidepression, and dependence.
Opioid Side Effects
- Respiratory depression
- Nausea and vomiting
- Pupil constriction
- Constipation
- Euphoria
- Itching
- Tolerance and dependence
Tolerance and Dependence
- Tolerance means the same amount of the drug produces less of an effect over time.
- Dependence means there's a physical need for an ongoing supply of the drug.
- Psychological dependence is when euphoria promotes a strong desire for further consumption of the drug.
- Withdrawal symptoms occur if the drug is stopped abruptly or an antagonist is introduced.
Endogenous Opioid Peptides
- These are pentapeptides, like Met-enkephalin and Leu-enkephalin, created by the body to relieve pain.
- Other endogenous opioid peptides include Beta-endorphin and Dynorphins.
Morphine
- Morphine is the main alkaloid in opium with analgesic properties.
- Its poor oral bioavailability meant it was rarely used medically until the hypodermic syringe was invented in 1853.
- It works in the brain by increasing the pain threshold and reducing pain awareness.
- It's highly effective in handling severe pain situations such as cancer, post-operative pain, and serious injuries.
- Morphine itself is poorly soluble in water. Salts are used in medical applications, such as hydrochloride or sulfate.
- The levo (-) isomer has analgesic properties, while the dextro (+) isomer possesses antitussive properties.
Morphine Metabolism
- Morphine is metabolized primarily via glucuronidation, resulting in morphine-3-glucuronide (inactive) and morphine-6-glucuronide (more active than morphine).
- A minor pathway involves N-demethylation, resulting in normorphine (lesser activity).
Morphine Analogues
- The structures of morphine can be adjusted to develop analogues with enhanced or decreased effects, altered side effects, or different routes of administration.
Aims of Opioid Drug Design - Analogues
- Analogues should maintain the analgesic action of morphine.
- They should contain important binding groups.
- They should be able to cross the blood-brain barrier.
- They should have reduced side effects.
- They should have better oral bioavailability.
- Structures are modified to alter pharmacokinetic and pharmacodynamic properties for specific drug actions.
Codeine
- Codeine is derived from morphine via a 3-methoxy substitution.
- It produces mild-to-moderate pain relief and is often used as an antitussive.
- It exhibits weaker analgesic effects and comparatively milder side effects than morphine.
- Has lower abuse risk.
Heroin
- Heroin is a diacetyl derivative of morphine, which makes it more lipid soluble.
- It exhibits increased potency and quicker onset of action due to its increased ability to cross the blood-brain barrier.
- Increased euphoria when injected compared to other routes
- Has a higher risk of dependence and addiction.
Opioid Agents Used as Cough Suppressants/Antitussives
- The rigid-structured opioids have cough suppressant action (antitussive activity) but it's not a primary opioid effect, it is not always antagonized by opioid antagonists.
- The 3-OCH3 derivatives of morphine are nearly as effective as free phenolic agents.
Hydromorphone
- A 7, 8-dihydro-6-keto derivative of morphine.
- More potent and better absorbed than morphine.
- Shows high lipid solubility, meaning it effectively crosses the blood-brain barrier.
- Primarily acts on µ-opioid receptors.
- More addictive than morphine.
Oxymorphone
- A 7,8-dihydro-6-keto + 14β-OH derivative of morphine.
- Higher potency (oral and parenteral) compared to morphine.
- Used chiefly as an analgesic drug/treatment.
- Has noticeable antidepressant effects.
Dextromethorphan
- A morphinan that lacks the 4,5-epoxide bridge in morphine.
- The levo isomer has potent opioid activity, while the dextro isomer exhibits potent antitussive action.
- Lacks analgesic, respiratory depressant, and µ-opioid agonist effects found in morphine.
Phenazocine
- A benzomorphan with a weaker analgesic action compared to morphine.
- It retains the original opioid qualities of morphine.
- Demonstrates the comparable addictive characteristics of morphine.
Meperidine
- The first entirely synthetic analgesic with morphine-like action.
- Short duration of activity is due to metabolism by esterases into a zwitterionic metabolite.
- Used in obstetrics (childbirth) for fast onset of action and controlled pain relief without excessive respiratory depression in newborns.
- Similar side effects to morphine, including abuse potential.
Fentanyl
- An anilidopiperidine that exhibits powerful analgesic effects.
- Exhibits 80-100 times higher potency or potency than morphine.
- Used for chronic pain management and in cancer patients, usually as a first-choice.
- Shows less tendency to cause respiratory depression than morphine.
Methadone
- A full opioid agonist.
- Very potent and has a lengthy duration of action.
- It's often used for the maintenance treatment of opioid addiction and/or chronic pain management.
- It displays fewer unwanted side effects compared to morphine.
Tramadol
- A centrally acting µ-opioid receptor agonist with SNRI (serotonin/norepinephrine reuptake inhibitor) properties..
- Possesses weak agonistic properties towards κ and δ opioid receptors.
- Shows 6,000-times lower affinity towards μ opioid receptors compared to morphine.
- It's often used as a less potent analgesic.
Nalorphine and Nalbuphine
- These are mixed opioid agonist-antagonists, primarily κ agonists and μ antagonists.
- Used occasionally to treat opioid overdoses.
- They exhibit rapid onset of action and are effective for moderating to severe pain.
Naloxone and Naltrexone
- Powerful opioid antagonists.
- Used for reversing opioid overdoses or treating opioid use disorders.
- Naloxone has a fast onset of action.
- Naltrexone shows longer lasting effects compared to naloxone.
Structure-Activity Relationships for Opioids
- Various structural modifications in morphine analogues influence their activities (analgesic, antitussive, addictive behaviors) and side effects.
Acetaminophen
- The only analgesic available through oral, rectal, and intravenous routes.
- No anti-inflammatory action.
- It does not hamper the function of platelets like aspirin.
- Lower risk of gastrointestinal ulcers.
- A highly effective analgesic and antipyretic drug.
- An important part of treatment protocol for fevers, mild to moderate pain, and in situations where conventional NSAIDs is inappropriate.
Mechanisms of Action of Acetaminophen
- The precise mechanism is still being researched.
- Current hypothesis include central COX isoenzyme inhibition (COX-3).
- Competitive antagonism with PGG₂ for its transformation to PGH₂ by COX enzymes.
- Depletion of glutathione stores reducing PGE production..
Acetaminophen Metabolism (Toxicity)
- Excessive dosage or combined usage with alcohol/caffeine can lead to a buildup of a toxic metabolite that causes liver dysfunction.
- This toxic metabolite is reduced by glutathione, however, excess acetaminophen overwhelms the glutathione reserve and results in severe injury or damage.
- Several factors heighten acetaminophen toxicity, including high doses, alcohol consumption, caffeine intake, and health conditions like malnutrition.
Gout Treatment
- Acute Gout: NSAIDs, corticosteroids, colchicine.
- Chronic Gout: Uricosuric drugs (probenecid, sulfinpyrazone) to enhance uric acid excretion or xanthine oxidase inhibitors (allopurinol, febuxostat) to reduce uric acid synthesis.
Colchicine
- Obtained from the Colchicum plant.
- Primarily controls acute gouty arthritis by inhibiting the inflammatory response but not altering uric acid levels.
- Mechanism of action involves inhibiting the production of lactic acid to prevent urate crystal deposition or inflammatory aspects.
- Usually the second treatment route when NSAIDs or glucocorticoids are ineffective.
Uricosuric Drugs (e. g., Probenecid, Sulfinpyrazone)
- Increases uric acid excretion from kidneys.
- Effective if kidney function is not compromised.
- Primarily used for preventing recurrent gout attacks.
Xanthine Oxidase Inhibitors (e.g., Allopurinol, Febuxostat)
- Reduces uric acid synthesis by inhibiting enzymes.
- More effective in lowering uric acid levels than uricosuric drugs and thus prevents gout formation.
Summary of Gout Treatment
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Description
Test your knowledge on the characteristics and derivatives of opioids like heroin, morphine, and codeine. This quiz covers aspects such as analgesic potency, abuse potential, and antitussive properties. Discover how different structural changes in morphine can affect its efficacy and side effects.
