Evaluation of a pharmacist-led naloxone coprescribing program in primary care.

OBJECTIVES: To determine the impact of a pharmacist-led coprescribing initiative on patient access to naloxone in a primary care setting. SETTING: Family medicine residency practice with embedded pharmacists in western North Carolina. PRACTICE INNOVATION: In June 2016, clinical pharmacists embedded in a primary care clinic initiated a naloxone coprescribing initiative with the aim of increasing access to naloxone for patients on chronic opioid therapy who were on 50 mg or greater morphine-equivalents daily (MED), on a concomitant benzodiazepine, had a history of an overdose, or had a diagnosis of a substance use disorder. Pharmacists' roles included educating providers and clinical staff regarding naloxone, creating quick links within the electronic health record to more easily prescribe naloxone, identifying patients who met criteria for naloxone, and counseling patients about naloxone. EVALUATION: This study was a single-cohort pre- and postintervention study. One year after initiation of the program, data were manually collected to assess the rates of naloxone prescribing and the reason for requiring naloxone. In addition, pharmacy students called pharmacies to determine fill rates and obtain reasons given by patients for not filling naloxone. RESULTS: A total of 234 patients remained candidates for naloxone at the end of 1 year. Naloxone coprescribing increased from 3.4% at baseline to 37.2% at follow-up (P = 0.0001). Seventy-one percent of patients required naloxone because of chronic opioid therapy doses of 50 mg or more MED, 55% were on a benzodiazepine, 6% had a diagnosis of a substance use disorder, and 1% had a history of overdose. Of the patients who received a naloxone prescription, 31.4% filled it. CONCLUSION: Embedded clinical pharmacists in primary care have the potential to increase naloxone coprescribing for high-risk patients treated with chronic opioid therapy for pain.

Differential modulation of drug-induced structural and functional plasticity of dendritic spines.

Drug-induced plasticity of excitatory synapses has been proposed to be the cellular mechanism underlying the aberrant learning associated with addiction. Exposure to various drugs of abuse causes both morphological plasticity of dendritic spines and functional plasticity of excitatory synaptic transmission. Chronic activation of µ-opioid receptors (MOR) in cultured hippocampal neurons causes two forms of synaptic plasticity: loss of dendritic spines and loss of synaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. With use of live imaging, patch-clamp electrophysiology, and immunocytochemistry, the present study reveals that these two forms of synaptic plasticity are mediated by separate, but interactive, intracellular signaling cascades. The inhibition of Ca(2+)/calmodulin-dependent protein kinase II with 1-[N,O-bis(5-isoquinolinesulfonyl)-N-methyl-l-tyrosyl]-4-phenylpiperazine (KN-62) blocks MOR-mediated structural plasticity of dendritic spines, but not MOR-mediated cellular redistribution of GluR1 and GluR2 AMPA receptor subunits. In contrast, the inhibition of calcineurin with tacrolimus (FK506) blocks both cellular processes. These findings support the idea that drug-induced structural and functional plasticity of dendritic spines is mediated by divergent, but interactive, signaling pathways.