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  • Pgx-Guided Dosing in Pain Management: (Group 7)

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    Michelle Kristine Donnelly
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    1. The WHO analgesic ladder recommends using non-opioid analgesics like NSAIDs for mild pain first before progressing to stronger opioids if pain is more severe and persistent. Codeine has a strong relationship to CYP2D6 metabolism and certain patients are at higher risk of toxicity. 2. The CPIC guidelines recommend avoiding codeine for ultrarapid and poor metabolizers due to toxicity risks and lack of efficacy, respectively. Normal metabolizers can use the standard dose but intermediate metabolizers should be monitored and may require an alternative. 3. Strong CYP2D6 inhibitors can increase the activity score while moderate inhibitors decrease it, affecting codeine dosing recommendations.

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    Personalized medicine lecture 1 pharmacotherapy pharm.

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    1. Pain Management

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    1. The WHO analgesic ladder recommends using non-opioid analgesics like NSAIDs for mild pain first before progressing to stronger opioids if pain is more severe and persistent. Codeine has a strong relationship to CYP2D6 metabolism and certain patients are at higher risk of toxicity. 2. The CPIC guidelines recommend avoiding codeine for ultrarapid and poor metabolizers due to toxicity risks and lack of efficacy, respectively. Normal metabolizers can use the standard dose but intermediate metabolizers should be monitored and may require an alternative. 3. Strong CYP2D6 inhibitors can increase the activity score while moderate inhibitors decrease it, affecting codeine dosing recommendations.

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    Pgx-Guided Dosing in Pain Management: (Group 7)

    Uploaded by

    Michelle Kristine Donnelly
    1. The WHO analgesic ladder recommends using non-opioid analgesics like NSAIDs for mild pain first before progressing to stronger opioids if pain is more severe and persistent. Codeine has a strong relationship to CYP2D6 metabolism and certain patients are at higher risk of toxicity. 2. The CPIC guidelines recommend avoiding codeine for ultrarapid and poor metabolizers due to toxicity risks and lack of efficacy, respectively. Normal metabolizers can use the standard dose but intermediate metabolizers should be monitored and may require an alternative. 3. Strong CYP2D6 inhibitors can increase the activity score while moderate inhibitors decrease it, affecting codeine dosing recommendations.

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    PGx-Guided Dosing in Pain Management (Group 7)

    1. WHO “Remodeled” analgesic ladder for chronic pain. Goes up and down. Step 1 Non-opioid analgesics NSAIDs,
    up to Nerve block and epidurals.
    Role of Opioids in Acute Pain: Multimodal analgesia recommended. Immediate release preferred over LA formulation. Mod:
    Codeine, Hydrocodone, Severe: oxycodone, morphine, hydromorphone, fentanyl. Avoid opioids when possible, try non-
    pharms and non-opioid analgesics first, but if pain is severe & persistent, opioids are indicated. Weaker for mild pain,
    stronger opioids for more severe.
    2D6 alleles are characterized based on enzymatic act: Wild type-norm func (AV = 1), Reduced function (AV = 0.5), Non-
    functional (AV = 0). Patients can have > 2 copies of the 2D6 (gene duplication). Activity score = sum of activity values.
    Codeine = STRONG relationship between 2d6 and opioid-related outcomes. ~5-15% of Codeine prodrug is
    metabolized by liver 2D6 to morphine, the active metabolite, with 250* affinity for opioid receptor.
    Tramadol = SOME relationship between 2D6 and opioid related outcome. Tramadol 200x  affinity.
    Hydrocodone, Oxycodone = POOR relationship. Hydrocodone 10-20x  affinity, Oxycodone ~11% metabolized to
    oxymorphone 40x  affinity, 8x higher potency for mu opioid receptor.
    3) What do the CPIC guidelines recommend regarding CYP2D6 genotype and treatment with opioid drugs? 


    Phenotype Phenotype Details Recommendation for Considerations for


    codeine therapy alternative opioids

    Ultrarapid enzyme activity. Avoid codeine - potential Alt not affected by this
    metabolizer  formation of morphine for toxicity. 2D6: Morph, oxymorph,
    Activity score >2.0 following codeine buprenorphine, fentanyl,
    administration, leading to methadone, etc.
    higher risk of toxicity. Other non-opioid analgesics

    Normal metabolizer Normal enzyme activity. Use label-recommended None


    Activity score 1.0-2.0 Normal morphine formation. age- or weight-specific
    dosing

    Intermediate Intermediate enzyme activity. Use label-recommended Monitor tramadol use for
    metabolizer Reduced morphine formation. dose. response
    Activity score 0.5 If no response, consider alt
    ex. Morphine/nonopioid

    Poor metabolizer Low or absent enzyme activity. Avoid codeine - lack of Alt not affected by this
    Activity score 0 Greatly reduced morphine efficacy 2D6: Morphine, oxymorph,
    formation following codeine buprenorphine, fentanyl,
    administration, leading to methadone, etc.
    insufficient pain relief. Other nonopioid analgesics

    Strong 2C6 inhibitors: Adjust activity score by 0. Weak – mod inhibitors: Multiply activity score by 0.5.
    Strong Moderate Weak

    Bupropion Cimetidine Amiodarone


    Fluoxetine Cinacalcet Celecoxib
    Paroxetine Duloxetine Clobazam
    Quinidine Fluvoxamine Desvenlafaxine
    Terbinafine Mirabegron Escitalopram

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