MedGen

Codeine, an opioid analgesic, is used for the treatment of pain. It is metabolized by cytochrome P450-2D6 (CYP2D6) to morphine, an active metabolite with pain-relief action. The CYP2D6 gene has many polymorphisms that result in different enzyme activities. An individual can be an ultrarapid, normal, intermediate, or poor metabolizer of codeine, based on their CYP2D6 genotype. The CYP2D6 ultrarapid phenotype is associated with a higher risk of severe toxicity when treated with codeine, due to increased metabolism of codeine and thus enhanced morphine formation. Conversely, the CYP2D6 poor metabolizer phenotype is associated with ineffective pain relief from codeine treatment due to reduced formation of morphine. Accordingly, therapeutic recommendations for codeine based on an individual’s CYP2D6 genotype have been published by the Clinical Pharmacogenetics Implementation Consortium (CPIC) in Clinical Pharmacology and Therapeutics and are available on the PharmGKB website. [from PharmGKB]

Tramadol, an opioid analgesic, is used for the treatment of pain. It is metabolized by cytochrome P450-2D6 (CYP2D6) to O-desmethyltramdol, an active metabolite with pain-relief action. The CYP2D6 gene has many polymorphisms that result in different enzyme activities. An individual can be an ultrarapid, normal, intermediate, or poor metabolizer of tramadol, based on their CYP2D6 genotype. The CYP2D6 ultrarapid phenotype is associated with a higher risk of severe toxicity when treated with tramadol, due to increased metabolism of tramadol and thus enhanced formation of the active metabolite. Conversely, the CYP2D6 poor metabolizer phenotype is associated with ineffective pain relief from tramadol treatment due to reduced formation of the active metabolite. Accordingly, therapeutic recommendations for tramadol based on an individual’s CYP2D6 genotype have been published by the Clinical Pharmacogenetics Implementation Consortium (CPIC) in Clinical Pharmacology and Therapeutics and are available on the PharmGKB website. [from PharmGKB]

Opioid addiction is a long-lasting (chronic) disease that can cause major health, social, and economic problems. Opioids are a class of drugs that act in the nervous system to produce feelings of pleasure and pain relief. Some opioids are legally prescribed by healthcare providers to manage severe and chronic pain. Commonly prescribed opioids include oxycodone, fentanyl, buprenorphine, methadone, oxymorphone, hydrocodone, codeine, and morphine. Some other opioids, such as heroin, are illegal drugs of abuse.

Opioid addiction is characterized by a powerful, compulsive urge to use opioid drugs, even when they are no longer required medically. Opioids have a high potential for causing addiction in some people, even when the medications are prescribed appropriately and taken as directed. Many prescription opioids are misused or diverted to others. Individuals who become addicted may prioritize getting and using these drugs over other activities in their lives, often negatively impacting their professional and personal relationships. It is unknown why some people are more likely to become addicted than others.

Opioids change the chemistry of the brain and lead to drug tolerance, which means that over time the dose needs to be increased to achieve the same effect. Taking opioids over a long period of time produces dependence, such that when people stop taking the drug, they have physical and psychological symptoms of withdrawal (such as muscle cramping, diarrhea, and anxiety). Dependence is not the same thing as addiction; although everyone who takes opioids for an extended period will become dependent, only a small percentage also experience the compulsive, continuing need for the drug that characterizes addiction.

Opioid addiction can cause life-threatening health problems, including the risk of overdose. Overdose occurs when high doses of opioids cause breathing to slow or stop, leading to unconsciousness and death if the overdose is not treated immediately. Both legal and illegal opioids carry a risk of overdose if a person takes too much of the drug, or if opioids are combined with other drugs (particularly tranquilizers called benzodiazepines). [from MedlinePlus Genetics]

Oxycodone is an opioid analgesic used for moderate to severe pain caused by various conditions for which alternative analgesic treatments are inadequate. Oxycodone exerts its analgesic affects by binding to the mu-opioid receptors (MOR) in the central and peripheral nervous system. While it is an effective pain reliever, this agent also has a high potential for addiction, abuse, and misuse. Oxycodone is metabolized by members of the cytochrome P450 (CYP) enzyme superfamily. The CYP3A4, CYP3A5, and CYP2D6 enzymes convert oxycodone to either less-active (CYP3A4 and CYP3A5) or more-active (CYP2D6) metabolites. Most of the analgesic effect is mediated by oxycodone itself, rather than its metabolites. Variation at the CYP3A4 and CYP3A5 loci leading to altered enzyme activity is rare. A handful of altered-function alleles are known, but there is no documented evidence to support altered oxycodone response in the presence of these variant alleles. The FDA approved drug label for oxycodone cautions that co-medication with CYP3A inhibitors or inducers may lead to altered pharmacokinetics and analgesia, but does not discuss genotype-based recommendations for prescribing. Genetic variation at the CYP2D6 locus has conflicting evidence regarding altered response of individuals to oxycodone therapy. Thus, the Clinical Pharmacogenetics Implementation Consortium (CPIC) has determined that there is insufficient evidence to recommend alterations to standard clinical use based on CYP2D6 genotype. Similarly, the Dutch Pharmacogenetics Working Group (DPWG) of the Royal Dutch Association for the Advancement of Pharmacy (KNMP) recognizes the drug-gene interaction between CYP2D6 and oxycodone but states that the interaction does not affect analgesia achieved by the medication. The PharmGKB online resource reports that drug labels in Switzerland (regulated by Swissmedic) state that CYP2D6 variation can alter oxycodone response. Interactions among drugs from polypharmacy may be further enhanced by genetic variation, but there are no professional recommendations to alter prescribing based on drug-drug-gene interactions. Regardless of genotype, oxycodone is contraindicated in individuals with significant respiratory depression, acute or severe bronchial asthma, known or suspect gastrointestinal obstruction, or known hypersensitivity to the medication [from Medical Genetics Summaries]

Hydrocodone, an opioid analgesic, is used for the treatment of pain. It is metabolized by cytochrome P450-2D6 (CYP2D6) to hydromorphone, an active metabolite with pain-relief action. The CYP2D6 gene has many polymorphisms that result in different enzyme activities. An individual can be an ultrarapid, normal, intermediate, or poor metabolizer of hydrocodone, based on their CYP2D6 genotype. CYP2D6 intermediate and poor metabolizers may have a reduced analgesic response to hydrocodone due to decreased metabolism of hydrocodone to hydromorphone. Accordingly, therapeutic recommendations for hydrocodone based on an individual’s CYP2D6 genotype have been published by the Clinical Pharmacogenetics Implementation Consortium (CPIC) in Clinical Pharmacology and Therapeutics and are available on the PharmGKB website. [from PharmGKB]

A substance abuse that involves the recurring use of opioid drugs despite negative consequences. [from MONDO]