Is codeine safe for everyone?

Codeine, an opioid analgesic, is commonly used to relieve mild to moderate pain. However, codeine requires enzymatic activation to convert into its active form, morphine, which is responsible for its analgesic effects.

The CYP2D6 gene plays a crucial role in the metabolism of codeine. However, there are genetic variations in the CYP2D6 gene that can lead to significant differences in CYP2D6 enzyme activity. Some individuals have normal CYP2D6 gene activity (known as normal metabolizers), while others may have reduced activity (slow metabolizers) or increased activity (ultrarapid metabolizers).

Slow metabolizers of codeine may experience a reduction in the effectiveness of the medication, as the conversion to morphine is limited. On the other hand, ultrarapid metabolizers may experience excessive conversion of codeine to morphine, which can lead to morphine accumulation and an increased risk of side effects, including respiratory depression.

The article "Pharmacogenetics of morphine poisoning in a breastfed neonate of a codeine-prescribed mother. Lancet. 2006 Aug 19;368(9536):704" describes the clinical case of a deceased newborn due to high levels of morphine in the blood. The newborn was breastfed by a mother who had received codeine for episiotomy pain. The mother was an ultrarapid metabolizer of CYP2D6, producing excessive levels of morphine that were transferred to the newborn through breast milk.

In clinical practice, genetic testing can be performed to identify the CYP2D6 metabolizer phenotype and help guide dosage and selection of alternative medications in patients receiving codeine. These tests can help personalize treatment and reduce the risk of side effects or lack of response to codeine.

It is important to note that the pharmacogenetics of codeine is only one part of the complete picture. Other factors, such as age, weight, presence of other diseases, and drug interactions, can also influence the individual response to codeine. Therefore, it is crucial for doctors to carefully evaluate each clinical situation and consider multiple factors when prescribing and administering codeine to patients.

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