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Questions and Answers
Which of the following statements is true regarding oxymorphone?
Which of the following statements is true regarding oxymorphone?
N-demethylation of oxycodone is primarily facilitated by CYP3A4.
N-demethylation of oxycodone is primarily facilitated by CYP3A4.
True
What percentage of oxycodone is excreted unchanged?
What percentage of oxycodone is excreted unchanged?
10%
The glucuronide conjugates of oxycodone contribute to approximately _____ of its analgesic effect.
The glucuronide conjugates of oxycodone contribute to approximately _____ of its analgesic effect.
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Match the oxycodone metabolites with their properties:
Match the oxycodone metabolites with their properties:
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Which of the following is considered a key enzyme in Phase I metabolism of opioids?
Which of the following is considered a key enzyme in Phase I metabolism of opioids?
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The primary goal of metabolism is to make lipophilic molecules more hydrophilic for easier excretion.
The primary goal of metabolism is to make lipophilic molecules more hydrophilic for easier excretion.
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Name one of the opioid analgesics that has significant active metabolites.
Name one of the opioid analgesics that has significant active metabolites.
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Phase II metabolism involves the introduction of _______ species.
Phase II metabolism involves the introduction of _______ species.
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Match the opioid analgesic with its characteristic:
Match the opioid analgesic with its characteristic:
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What is the estimated potency ratio of morphine-6-glucuronide (M3G) compared to morphine?
What is the estimated potency ratio of morphine-6-glucuronide (M3G) compared to morphine?
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Morphine-3-glucuronide (M3G) is believed to have a significant contribution to analgesic activity when compared to morphine.
Morphine-3-glucuronide (M3G) is believed to have a significant contribution to analgesic activity when compared to morphine.
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What is the risk associated with renal failure regarding the accumulation of morphine metabolites?
What is the risk associated with renal failure regarding the accumulation of morphine metabolites?
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The inactive metabolite of codeine is known as codeine-6-________.
The inactive metabolite of codeine is known as codeine-6-________.
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Match the following substances with their respective characteristics:
Match the following substances with their respective characteristics:
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What percentage of morphine is typically converted to morphine-6-glucuronide (M6G)?
What percentage of morphine is typically converted to morphine-6-glucuronide (M6G)?
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Codeine-6-glucuronide is active and contributes to the analgesic effects of codeine.
Codeine-6-glucuronide is active and contributes to the analgesic effects of codeine.
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What does UGT2B7 stand for?
What does UGT2B7 stand for?
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In Phase II metabolism, phenols mainly conjugate with __________ or sulfate.
In Phase II metabolism, phenols mainly conjugate with __________ or sulfate.
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Match the following substances with their descriptions:
Match the following substances with their descriptions:
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Which of the following statements is true regarding Phase II conjugation in the GI tract?
Which of the following statements is true regarding Phase II conjugation in the GI tract?
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Morphine is primarily converted to active metabolites in Phase I metabolism.
Morphine is primarily converted to active metabolites in Phase I metabolism.
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What impact does Phase II conjugation have on the oral bioavailability of opioids?
What impact does Phase II conjugation have on the oral bioavailability of opioids?
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Which metabolite of tramadol has analgesic activity?
Which metabolite of tramadol has analgesic activity?
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M3G is an active metabolite of morphine.
M3G is an active metabolite of morphine.
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What enzymes are primarily responsible for the formation of tramadol metabolites?
What enzymes are primarily responsible for the formation of tramadol metabolites?
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Morphine-6-glucuronide (M6G) is ______ times more potent than morphine following intrathecal administration.
Morphine-6-glucuronide (M6G) is ______ times more potent than morphine following intrathecal administration.
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Match the following metabolites with their properties:
Match the following metabolites with their properties:
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Which metabolite has the highest affinity for the mu-opioid receptor (MOR)?
Which metabolite has the highest affinity for the mu-opioid receptor (MOR)?
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M6G leads to less respiratory depression compared to morphine.
M6G leads to less respiratory depression compared to morphine.
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What is the primary function of (-)-Tramadol in the context of tramadol metabolism?
What is the primary function of (-)-Tramadol in the context of tramadol metabolism?
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What is the verbal rating scale used for measuring pain intensity in PCA?
What is the verbal rating scale used for measuring pain intensity in PCA?
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A person with two non-functional alleles is considered an extensive metaboliser.
A person with two non-functional alleles is considered an extensive metaboliser.
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What is the percentage range for the metabolism of codeine by UGT2B7?
What is the percentage range for the metabolism of codeine by UGT2B7?
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The _____ metaboliser phenotype has the highest population incidence in Ethiopians.
The _____ metaboliser phenotype has the highest population incidence in Ethiopians.
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Which of the following genotypes corresponds to a poor metaboliser phenotype?
Which of the following genotypes corresponds to a poor metaboliser phenotype?
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CYP2D6-catalysed metabolism is a minor clearance mechanism for some drugs.
CYP2D6-catalysed metabolism is a minor clearance mechanism for some drugs.
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Which population has a 21% incidence of ultrarapid metaboliser phenotype?
Which population has a 21% incidence of ultrarapid metaboliser phenotype?
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Match the populations with their corresponding incidence rates for poor metaboliser phenotype:
Match the populations with their corresponding incidence rates for poor metaboliser phenotype:
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Study Notes
ADME 1: Acute Pain 5 - Opioid Analgesics
- The metabolism and pharmacogenetics of opioid analgesics are discussed in this presentation
- Learning objectives include describing major metabolic routes and transformations, active metabolites' importance, and morphine/metabolite pharmacokinetics.
- Another aspect is pharmacogenetics: explaining genetic variation's effect on metabolism, providing population phenotype examples, and how phenotypes influence common opioid metabolism.
- Metabolism aims to remove xenobiotics, transforming lipophilic molecules into more hydrophilic ones for excretion.
- Phase I modification involves adding chemical functionality (oxidation, hydrolysis, reduction) with key enzymes like CYP450 monooxygenases.
- Phase II conjugation introduces charged/polar species (e.g., sulfation, glucuronidation, GSH conjugation) with key enzymes such as sulfotransferases and UDP glucuronosyltransferases.
- The presentation gives main metabolic pathways and active metabolites for various opioids (buprenorphine, codeine, fentanyl, morphine, oxycodone, tramadol).
- Morphine and Codeine phase-1 metabolism includes N-demethylation (CYP3A4) and O-demethylation (CYP2D6).
- Nor-metabolites have limited clinical relevance, and patients deficient in CYP2D6 have reduced codeine effectiveness.
- Morphine and Codeine phase-2 metabolism details conjugation with glucuronic acid or sulfate.
- The conjugates are typically inactive and found in urine.
- Phase II conjugation in the GI tract significantly impacts oral bioavailability of phenolic opioids, increasing polarity.
- Morphine-6-glucuronide (M6G) is more active than morphine.
- M6G can accumulate in renal impairment, increasing overdose risk.
- Oxycodone metabolism involves oxymorphone formation through N-demethylation (CYP3A4).
- Noroxycodone is less potent than oxycodone.
- Tramadol has a complex metabolism with 11 metabolites, with (+)-M1 having significant analgesic activity.
- (-)-M1 has minimal analgesic activity, and the metabolite formation depends on CYP2D6 and CYP3A4.
- The presentation also describes various pharmacokinetic properties like oral bioavailability, protein binding, volume of distribution, half-life, and excretion of common opioids.
- Morphine-3-glucuronide (M3G) is an inactive metabolite potentially associated with neurotoxic effects (e.g., myoclonus).
- M3G and M6G have longer half-lives than morphine. Plasma concentrations of M3G and M6G are usually higher than morphine.
- Metabolites accumulate in renal impairment.
Pharmacogenetics of Opioid Analgesics
- CYP2D6 genetic variations affect opioid metabolism, categorized as extensive (EM), intermediate (IM), poor (PM), and ultrarapid (UM) metabolizers.
- Different genotypes correspond to these phenotypes.
- Poor metabolizers have limited codeine effectiveness due to impaired O-demethylation, leading to low morphine plasma concentrations.
- Conversely, ultrarapid metabolizers experience extensive metabolism of codeine to morphine, potentially increasing opioid side effects.
- Variations in CYP2D6 can affect tramadol metabolism, impacting (+)-M1 formation and increasing side effects.
Environmental Factors
- Patient age, sex, hepatic and renal function, smoking, alcohol consumption, and concurrent medications influence opioid metabolism.
Summary
- Active metabolites contribute to analgesic effects.
- Pharmacogenetic differences and handling differences for analgesics, pain severity, individual response, and analgesic dose are difficult to predict.
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Description
Explore the metabolism and pharmacogenetics of opioid analgesics in this quiz. Learn about key metabolic routes, the importance of active metabolites, and how genetic variations affect opioid metabolism. Dive into Phase I and II modifications to understand how the body processes these medications.
