Use of CYP2D6 substrates and inhibitors during pain management with analgesic opioids: Drug-drug interactions that lead to lack of analgesic effectiveness.

BACKGROUND: Several opioids have pharmacogenetic and drug-drug interactions which may compromise their analgesic effectiveness, but are not routinely implemented into supportive pain management. We hypothesized that CYP2D6 phenotypes and concomitant use of CYP2D6 substrates or inhibitors would correlate with opioid analgesic outcomes. MATERIALS AND METHODS: An observational cross-sectional study was conducted with 263 adult chronic non cancer pain (CNCP) patients from a real-world pain unit under long-term CYP2D6-related opioid treatment (tramadol, hydromorphone, tapentadol or oxycodone). Metabolizer phenotype (ultrarapid [UM], normal [NM], intermediate [IM] or poor [PM]) was determined by the CYP2D6 genotype. The socio-demographic (sex, age, employment status), clinical (pain intensity and relief, neuropathic component, quality of life, disability, anxiety and depression), pharmacological (opioid doses and concomitant pharmacotherapy) and safety (adverse events) variables were recorded. RESULTS: The whole population (66 % female, 65 (14) years old, 70 % retired and 63 % attended for low back pain) were classified as PM (5 %), IM (32 %), NM (56 %) and UM (6 %). Multiple linear and logistic regressions showed higher pain intensity and neuropathic component at younger ages when using any CYP2D6 substrate (p = 0.022) or inhibitor (p = 0.030) drug, respectively, with poorer pain relief when CYP2D6 inhibitors (p=0.030) were present. CONCLUSION: The concomitant use of CYP2D6 substrates or inhibitors during opioid therapy for CNCP may result in lack of analgesic effectiveness. This aspect could be relevant for pharmacological decision making during CNCP management.

Uptake of perfluorinated compounds by plants grown in nutrient solution.

The uptake rates of three perfluorinated carboxylates and three perfluorinated sufonates by a grass (B diandrus) grown in nutrient solution at two different perfluorinated compounds (PFCs) concentrations were assessed. Grass can be ingested by grazing animals causing the PFCs to enter the food chain, which is a pathway of human exposure to these compounds. A rapid and miniaturized method was developed to determine PFCs in plants, based on a matrix solid-phase dispersion (MSPD) extraction procedure followed by quantitation by HPLC-MS/MS with an MQL in the range from 1 to 9 ng/g. An increase of PFCs levels in plant was observed along the exposure time. Differences in uptake for studied perfluorinated carboxylates were found, showing a decrease with carbon chain length (from 3027 to 1,167 ng/g at the end of assay), whereas no significant differences in absorption were obtained between perfluorinated sulfonates (about 1,700 ng/g). Initially, higher PFC transfer factors (ratio between concentration in plant and concentration in initial nutrient solution) were obtained for plants growing in the nutrient solution at the highest PFC concentration, but these factors became similar with time to plants exposed to the lowest concentration.

Neurofribromatosis tipo 1 (von Recklinghausen). A propósito de una casuística pediátrica / Neurofibromatosis type 1 (von Recklinghausen). Based on a pediatric casuistics

Objetivos. Analizar la clínica y radiología de pacientes pediátricos afectos de NF1. Pacientes y métodos. Se estudian 33 pacientes diagnosticados de NF1 según los criterios del NIH. Resultados. Existe predominio -no significativo- de las mujeres. 28 pacientes (85 por ciento) presentan antecedentes familiares. Las manchas color café con leche son de presentación constante, asociadas a efélides en el 48,5 por ciento. El 36,4 por ciento presentaban fibromas, que eran plexiformes en el 15,5 por ciento; la escoliosis se observó en el 33,3 por ciento y el 3 por ciento mostraban pseudoartrosis y una hemihipertrofia facial. El 9 por ciento tenía retraso psicomotor , el 30 por ciento cefalea, el 9 por ciento crisis convulsivas, el 6 por ciento hiperactividad y el 3 por ciento temblor. La presencia de tumores se evidenció en el 12 por ciento y de UBOs en el 45 por ciento de los casos estudiados con RM. Conclusiones. La NF1 afecta a todos los órganos y, por su carácter evolutivo, obliga a efectuar controles periódicos. Las manchas de color café son una manifestación constante, por lo que su presencia en un lactante debe alertar al pediatra para la búsqueda de otras manifestaciones de la enfermedad. La radiología mostró tumores intracraneales en el 12 por ciento de los pacientes y los UBOs se evidenciaron en el 45 por ciento de los que fueron estudiados con RM encefálica (AU)