Pharmacogenetic Testing and Opioids
Pharmacogenetic Testing and Opioids
Codeine is an opioid analgesic that is related to morphine, with less potent analgesic properties. Codeine is selective for the mu receptor but with much weaker affinity than morphine. Once administered, codeine is metabolized to codeine-6-glucuronide (C6G), morphine, and norcodeine through different pathways. CYP2D6 is the major enzyme responsible for the conversion of codeine to morphine.
Normally, a patient converts approximately 10% of codeine to morphine for analgesia. There are many combinations of alleles, which determine metabolizer status that can be detected from PGT. Approximately 1% to 2% of patients are UMs (e.g., CYP2D6*1/*1XN ) and make up to 75% more morphine than non-UMs, substantially increasing their risk of toxicity. Alternative analgesics are recommended for CYP2D6 UMs. EMs and IMs produce normal morphine formation (e.g., CYP2D6*1/*1 and CYP2D6*4/*10, respectively). Ageor weight-specific codeine dosing is recommended in these types of metabolizers. Patients who are PMs (~5%-10% of the population) have greatly reduced morphine formation, leading to insufficient pain relief (e.g., CYP2D6*3/*6 ). Codeine should be avoided in these patients due to insufficient pain relief. Other opioid analgesics, which are not metabolized by the CYP2D6 enzyme system to active metabolites, include morphine, hydromorphone, oxymorphone, buprenorphine, and fentanyl. These alternatives are potentially safer than codeine in UM patients. Please refer to CASE 1 regarding the dosing of codeine.
Codeine
Codeine is an opioid analgesic that is related to morphine, with less potent analgesic properties. Codeine is selective for the mu receptor but with much weaker affinity than morphine. Once administered, codeine is metabolized to codeine-6-glucuronide (C6G), morphine, and norcodeine through different pathways. CYP2D6 is the major enzyme responsible for the conversion of codeine to morphine.
Normally, a patient converts approximately 10% of codeine to morphine for analgesia. There are many combinations of alleles, which determine metabolizer status that can be detected from PGT. Approximately 1% to 2% of patients are UMs (e.g., CYP2D6*1/*1XN ) and make up to 75% more morphine than non-UMs, substantially increasing their risk of toxicity. Alternative analgesics are recommended for CYP2D6 UMs. EMs and IMs produce normal morphine formation (e.g., CYP2D6*1/*1 and CYP2D6*4/*10, respectively). Ageor weight-specific codeine dosing is recommended in these types of metabolizers. Patients who are PMs (~5%-10% of the population) have greatly reduced morphine formation, leading to insufficient pain relief (e.g., CYP2D6*3/*6 ). Codeine should be avoided in these patients due to insufficient pain relief. Other opioid analgesics, which are not metabolized by the CYP2D6 enzyme system to active metabolites, include morphine, hydromorphone, oxymorphone, buprenorphine, and fentanyl. These alternatives are potentially safer than codeine in UM patients. Please refer to CASE 1 regarding the dosing of codeine.
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