Cebranopadol for the Treatment of Chronic Pain.

PURPOSE OF REVIEW: Regardless of the etiology, if pain persists chronically, it can detrimentally impact multiple aspects of a patient's well-being. Both physical and psychological effects are significant in many chronic pain patients. In this regard, psychological consequences can alter a patient's quality of life, functionality, and social functioning. Opioids have been the long-established gold standard for acute pain treatment in settings such as the postoperative period. An alternative to opioids in pain management has been highly sought after. Through a non-selective mechanism, cebranopadol is a first-in-class oral drug which combines agonism of the mu and nociceptin opioid peptide (NOP) receptors to provide improved analgesia, while reducing the occurrence of many typically opioid side effects. This manuscript is a narrative review of the possible use of cebranopadol in pain management. RECENT FINDINGS: In pre-clinical studies, cebranopadol was similar to morphine in its pain control efficacy. In a phase IIa trial, cebranopadol was superior to placebo in reducing pain. In a randomized clinical trial, cebranopadol was superior to morphine. Another study concluded that cebranopadol had a lower misuse potential when compared to hydromorphone. In summary, cebranopadol offers new opportunities in treating chronic moderate to severe pain, while also countering risks of addiction. Additional studies are warranted to further evaluate the safety and efficacy of cebranopadol. In this regard, cebranopadol could prove to be a promising alternative to current pain treatment options.

The Use of Oxytocin for the Treatment of Opioid Use Disorder.

Nearly 27 million people have an opioid use disorder (OUD) according to the 2016 Global Burden of Disease study, most of which occur in the US where opioids are a common class of medication used to treat acute and chronic pain. In 2016 alone, more than 60 million patients had at least one prescription for opioids filled or refilled. Over the past decade, prescription rates have risen astronomically and have created an epidemic in the US dubbed the "opioid crisis." In this regard, there has been an increase in overdoses and OUD diagnoses. Several studies have found dysregulation of balance between several neurotransmitters involved in the neural circuitry that subserves several behavioral domains, such as reward recognition, motivation, learning, and memory, affect, stress, and executive function, that contribute to the manifestation of craving. On the horizon is a new treatment approach consisting of the neuropeptide oxytocin, which may be involved in the overlapping mechanisms of stable attachment formation and coping with stress. Through this mechanism, it can shift processing from novelty and reward-seeking to an appreciation of familiarity and thus reduce stress and increase resilience in the face of addiction. It has been hypothesized that there is a connection between the glutaminergic and oxytocinergic systems, making oxytocin a possible therapeutic agent in reducing drug-induced actions seen in OUD patients. This manuscript will review the potential and feasible use of oxytocin in treating OUD.

The Evolving Role of Vericiguat in Patients With Chronic Heart Failure.

Heart failure (HF) is a chronic and progressive clinical disorder characterized by an inability to pump sufficient blood to meet metabolic demands. It poses a substantial global healthcare burden, leading to high morbidity, mortality, and economic impact. Current treatments for HF include lifestyle modifications, guideline-directed medical therapies (GDMT), and device interventions, but the need for novel therapeutic approaches remains significant. The introduction of vericiguat, a soluble guanylate cyclase stimulator, has shown promise in improving outcomes for heart failure patients. Vericiguat addresses the underlying pathophysiological mechanisms of heart failure by augmenting the cyclic guanosine monophosphate (cGMP) pathway, leading to enhanced cardiac contractility and vasodilation. Clinical trials evaluating the efficacy and safety of vericiguat, such as the Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction (VICTORIA) trial, have demonstrated promising results. It has been shown that vericiguat, when added to standard therapy, reduces the risk of HF hospitalization and cardiovascular death in patients with symptomatic chronic HF with reduced ejection fraction (HFrEF). The addition of vericiguat to the current armamentarium of HF treatments provides clinicians with a novel therapeutic option to further optimize patient outcomes. Its potential benefits extend beyond symptom management, aiming to reduce hospitalizations and mortality rates associated with HF. As with any new treatment, the appropriate patient selection, monitoring, and management of potential adverse effects are essential. Further research is warranted to determine the long-term benefits, optimal dosing strategies, and potential combination therapies involving vericiguat. Its ability to target the cGMP pathway provides a unique mechanism of action, offering potential benefits in improving clinical outcomes for HF patients. Continued investigation and clinical experience will further elucidate the role of vericiguat in the management of HF and its overall impact on reducing the healthcare burden associated with this debilitating condition.