ABSTRACT
The opioid medications codeine and hydrocodone, commonly prescribed in sickle cell disease (SCD), require metabolic conversion by cytochrome P450 2D6 (CYP2D6) to morphine and hydromorphone, respectively, to exert their analgesic effects. The CYP2D6 gene is highly polymorphic, with variant alleles that result in decreased, absent, or ultrarapid enzyme activity. Seventy-five children with SCD were tested for CYP2D6 polymorphisms, and metabolic phenotypes were inferred from the genotypes. The most common variant alleles were CYP2D6*2 (normal activity, 28.7%), CYP2D6*17 (reduced activity, 17.3%), CYP2D6*5 (gene deletion, 8.7%), and CYP2D6*4 (absent function, 8.0%). Normal/extensive metabolizer genotypes were found in 28/75 (37.5%), intermediate metabolism in 33/75 (44.0%), poor metabolism in 4/75 (5.3%), ultrarapid metabolism in 3/75 (4.0%), indeterminate in 6/75 (8.0%). Allele frequencies did not vary significantly among different hemoglobin genotypes. Identification of variant CYP2D6 genotypes may identify individuals with altered metabolism and therefore altered analgesic response to codeine and hydrocodone, thus providing a personalized medicine approach to treatment of pain in SCD. Further pharmacokinetic and pharmacodynamic studies are needed to define the relationship of CYP2D6 and other gene polymorphisms to individual opioid effect in SCD.
Subject(s)
Analgesics, Opioid/metabolism , Anemia, Sickle Cell/genetics , Anemia, Sickle Cell/metabolism , Black or African American/genetics , Cytochrome P-450 CYP2D6/genetics , Polymorphism, Genetic , Adolescent , Alleles , Child , Gene Frequency , Genotype , Humans , PhenotypeABSTRACT
The Physician Quality Reporting System (PQRS) uses a combination of payment incentives and adjustments to promote reporting of quality information by eligible professionals who satisfactorily report data on quality measures for covered Physician Fee Schedule services furnished to Medicare Part B Fee-for-Service beneficiaries. Physicians should become familiar with the PQRS core measures to maintain compliance with the Centers for Medicare & Medicaid Services. Adherence to these basic guidelines will allow physicians to not only maximize their income, but also increase quality of care, decrease complications, and decrease healthcare expenditures.
