Buprenorphine and its formulations: a comprehensive review.

Buprenorphine, a novel long-acting analgesic, was developed with the intention of two purposes: analgesia and opioid use disorder. Regarding its pharmacodynamics, it is a partial agonist at mu receptors, an inverse agonist at kappa receptors, and an antagonist at delta receptors. For the purpose of analgesia, three formulations of buprenorphine were developed: IV/IM injectable formulation (Buprenex®), transdermal patch formulation (Butrans®), and buccal film formulation (Belbuca®). Related to opioid dependence, the formulations developed were subcutaneous extended release (Sublocade®), subdermal implant (Probuphine®), and sublingual tablets (Subutex®). Lastly, in order to avoid misuse of buprenorphine for opioid dependence, two combination formulations paired with naloxone were developed: film formulation (Suboxone®) and tablet formulation (Zubsolv®). In this review, we present details of each formulation along with their similarities and differences between each other and clinical considerations.

Histopathological evidence that diethylene glycol produces kidney and nervous system damage in rats.

Diethylene glycol (DEG) is an organic compound that has been found as an adulterant in consumer products as a counterfeit glycerin. Diethylene glycol is metabolized to two primary metabolites: 2-hydroxyethoxyacetic acid (2-HEAA) and diglycolic acid (DGA), the latter shown to accumulate in the kidney and cause dose-dependent cell necrosis. DEG poisonings are characterized predominately by acute kidney injury (AKI) but have also produced delayed neurological sequelae such as sensorimotor neuropathy. To better understand these effects, Wistar-Han rats were orally administered a water control or doses of 4 g/kg-6 g/kg DEG every 12 or 24 h for 7 days, with kidney, brain, and spinal cord tissue collected for histopathological analysis. This dosing paradigm resulted in approximately 25 % of the DEG-treated animals developing AKI and also neurotoxicity (sensorimotor dysfunction and elevated cerebrospinal fluid (CSF) protein). Kidney pathology included a severe, diffuse acute kidney tubular necrosis predominantly affecting proximal convoluted tubules. Scattered birefringent crystals consistent with calcium oxalate monohydrate were also found in the proximal tubule of animals with AKI. Demyelination in the dorsal and lateral white matter regions of the cervical, thoracic, and lumbar areas of the spinal cord of a DEG-treated animal with AKI was documented, establishing the neuropathology in DEG-treated animals that developed neurotoxicity. There were significant changes in amino acid concentrations in the CSF that may reflect the neurotoxicity of DEG, specifically glutamate and glutamine, but with no ammonia change. These studies characterized the pathologic aspects of the neurotoxicity in a DEG repeat-dose model.

Role of Intravenous Lidocaine Infusion in the Treatment of Peripheral Neuropathy.

PURPOSE OF REVIEW: This is a comprehensive review of the literature regarding intravenous lidocaine infusion to treat peripheral neuropathy. The clinical symptoms of peripheral neuropathy occur on a broad spectrum and stem from many etiologies resulting in complex treatment approaches. This review presents the background, evidence, and indications for the use of intravenous lidocaine infusions as a treatment option for this condition. RECENT FINDINGS: The clinical range of peripheral neuropathy symptoms includes pain, numbness, muscle weakness, paresthesia, balance difficulty, and autonomic dysfunction. However, severe neuropathic pain remains one of the most debilitating symptoms that significantly affects the quality of life. Current treatment options include antidepressants, anticonvulsants, and, in some cases, opiates, but these are often ineffective, creating the need for other therapeutic approaches.The pathophysiology of neuropathic pain involves sodium channels which create abnormal pain responses. Intravenous lidocaine primarily functions by inhibiting membrane sodium channels which desensitize peripheral nociceptors, thus creating an analgesic effect. The research in using intravenous lidocaine for neuropathic pain is not fully complete and requires further evaluation. SUMMARY: Peripheral neuropathy is a manifestation commonly resulting from diabetes, alcohol abuse, vitamin deficiencies, and chemotherapy, among other causes. One of the most significant complications is neuropathic pain which is often resistant to multi-modal therapeutic regimens. Intravenous lidocaine infusions are a newer treatment option for neuropathic pain, which have additional anti-inflammatory effects with a minimal side effect profile. Studies have concluded it effectively treats neuropathic pain for weeks after administration, but results are variable depending on specific procedures. Further research, including additional direct comparison studies, should be conducted to fully evaluate this drug's usefulness.