CYP2D6 in the Metabolism of Opioids for Mild to Moderate Pain

Abstract

In most cancer patients, pain is successfully treated with pharmacological measures using opioid analgesics for moderate to severe pain (strong opioids) alone or in combination with adjuvant analgesics (coanalgesics). Opioids for mild to moderate pain (weak opioids) are usually recommended in the treatment of cancer pain of mild to moderate intensity. There is a debate whether the second step of the WHO analgesic ladder comprising weak opioids such as tramadol, codeine and dihydrocodeine is still needed for the treatment of cancer and chronic pain since low doses of strong opioids show similar efficacy. However, many patients with mild, moderate and in some cases strong pain intensity are still successfully treated with weak opioids. All these drugs are metabolized through CYP2D6, an important enzyme for approximately 25% of all drugs administered in clinical practice. The aim of this review is to summarize data on the impact of CYP2D6 polymorphism on pharmacokinetics, pharmacodynamics and adverse effects of weak opioids.

Pain Control in Head and Neck Cancer

“…Both mechanisms are implicated in neuropathic pain pathways. The metabolism of dihydrocodeine is not affected by CYP2D6 (Leppert, 2011).…”

“…There are many variants of the CYP2D6 enzyme, which impact upon the metabolism of weak opioids (Leppert, 2011). This polymorphism results in some people being "poor metabolisers", whereas some people are "extensive metabolisers".…”

Tramadol

“…People with the "poor metabolizer" phenotype have absent or reduced CYP2D6 activity and form less opioid metabolite for a given dose, which results in less analgesia. 1 The same is true of patients receiving medications that inhibit CYP2D6, such as paroxetine and bupropion. Conversely, patients exhibiting the "ultra-rapid metabolizer" phenotype are particularly prone to tramadol's opioid-like effects.…”

Genetic and Epigenetic Factors Affecting Cytochrome P450 Phenotype and Their Clinical Relevance

“…CYP2D6 polymorphism affects greatly the precent ratio of these metabolites, which means that PMs do not bioactivate enough codeine to morphine and EMs are at risk of CNS depression and other side effects due to elevated morphine production ( Table 2.) (Leppert, 2011).…”

“…Although DHM display greater affinity for opioid receptors than DHC, its pharmacological role in analgesic effect is not proven. Studies performed to date indicate that DHC analgesia is independent of CYP2D6 activity (Leppert, 2011).…”