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.

Loneliness impact on healthcare utilization in primary care: A retrospective study.

BACKGROUND: An increased number of patients seek help for loneliness in primary care. OBJECTIVE: To analyze whether loneliness was associated with a higher utilization of healthcare facilities. METHODS: Observational, retrospective study based on the review of routinely coded data in the digital medical record system in a random sample of patients aged 65 or older, stratified by population size of their residence area. A minimum sample size was estimated at 892 medical records. Loneliness was defined as the negative feeling that arises when there is a mismatch between the quantity and quality of a person's social relationships and those, they desire. Thirty-three primary care nurses (30 females and 3 males) were reviewing the data. RESULTS: A total of 932 medical records of patients were reviewed (72% belonged to female patients). Of these, 657 individuals were living alone (71.9%). DeJong Scale average scores was 8.9 points (SD 3.1, 95CI 8.6-9.1). The average annual attendance to primary care ranged from 12.2 visits per year in the case of family practice, 10.7 nurse, 0.7 social workers. The average number of home visits was 3.2, and the urgent consultations attended at health centers were 1.5 per year. Higher feelings of loneliness were associated with extreme values in the frequency of healthcare resource usage. Compared to their peers of the same age, the additional healthcare resource consumption amounted to €802.18 per patient per year. CONCLUSION: Loneliness is linked to higher healthcare resource usage in primary care, with individuals experiencing poorer physical and mental health utilizing these resources up to twice as much as their peers of the same age.

Methacholine induced headache.

A lung function technician developed episodes of headache, probably related to the use of methacholine. The headache disappeared with breathing 100% oxygen. Cholinergic agents are known to induce headaches but the mechanism remains unclear. Vascular factors could be implicated.