Expert Opinion on Pharmacotherapy最新文献

Introduction: Gastroesophageal reflux disease (GERD) is a common debilitating chronic disease presenting in two main forms based on esophageal mucosal appearance, the erosive reflux disease (ERD) and the non-erosive reflux disease (NERD). Acid secretion is a key factor in the disease pathogenesis and management. Potent acid-suppressant drugs have been manufactured since the mid of 1970s, initially with histamine-H2-receptors antagonists, and later, inhibitors of the proton pump (H+-K+-ATPase). More recently, potassium-competitive acid blockers (P-CABs), particularly Vonoprazan, have been introduced. Vonoprazan has shown high efficacy and safety profiles and exhibits several advantages that allow to overcome shortcomings of proton pump inhibitors (PPIs).

Areas covered: In this review, we provide an updated summary of Vonoprazan pharmacodynamics and its role in clinical practice for the management of erosive esophagitis and GERD related heartburn. Moreover, we discuss characteristics of Vonoprazan that allow to bypass some limitations of the older PPIs.

Expert opinion: Long-term safety and efficacy of Vonoprazan have already been demonstrated for the induction and maintenance of ERD, preventing nocturnal acid breakthrough, reducing reflux symptoms in non-responder to standard therapy. Ongoing and future studies are expected to further elucidate its long-term benefits and potential applications in other acid-related disorders.

Introduction: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) has been introduced as a superior term to describe steatosis on a background of metabolic dysregulation and is slated to become the leading cause of HCC worldwide, as the incidence of metabolic comorbidities is increasing. As such, MASLD has evolved into an important public health issue, potentially leading to higher rates of liver mortality and end-stage liver disease. To this end, understanding the association between MASLD and HCC may allow for the identification of better interventions and novel therapeutic strategies.

Areas covered: The authors provide a review of current knowledge on HCC development among patients with MASLD, with insights into molecular pathways and current and future therapeutic strategies.

Expert opinion: MASLD has a strong association with the risk of HCC development, as metabolic comorbidities induce dysregulation in molecular pathways, leading to insulin-resistance, oxidative stress, and chronic inflammation, thus causing progression to cirrhosis and eventually to HCC. Therapeutic strategies focused on reducing diabetes-associated complications, as well as the prevalence of obesity and smoking can improve patient outcomes and reduce HCC incidence. Future studies on the molecular background of metabolic alterations may help devise new therapeutic approaches aiming to improve the current management of MASLD-HCC.

Introduction: Recent data question the use of aspirin as a bedrock of antiplatelet therapy in patients with arterial diseases. There are controversies regarding the efficacy of aspirin therapy with respect to specific demographic characteristics, dose and formulations, benefit in primary prevention, and duration in secondary prevention. Importantly, to balance the ischemic benefits and the risk of excessive bleeding following a coronary event, recent studies have investigated strategies to discontinue aspirin therapy and continue with P2Y₁₂ receptor inhibitor monotherapy. But the precise time when to discontinue aspirin is still unresolved.

Areas covered: Evidence from recent studies evaluating the role of aspirin in primary and secondary prevention studies were collected from a selective literature search. In this review, the authors discuss current recommendations, large scale studies of aspirin therapy, controversies, and potential future opportunities for aspirin therapy.

Expert opinion: With the new evidence showing lower bleeding risk with aspirin free strategies in both primary and secondary prevention studies, the role of aspirin is being revaluated with P2Y₁₂ receptor inhibitor monotherapy. The potential benefit of novel aspirin formulations and alternative delivery methods, such as inhaled aspirin, are undergoing much needed investigation with the goal of optimizing care for a wide range of patients.

Introduction: Anorexia nervosa (AN) has one of the highest mortality rates of all mental illnesses. No approved pharmacological treatments exist for AN, but novel neurobiological targets show promise.

Areas covered: Studies show that in individuals with AN, there are alterations in brain neurotransmitter signaling, alongside associated mental rigidity and comorbid anxiety and depression. Available and new therapies could be used to improve alterations in neurobiology and behavior. This narrative review serves as a review of previously published literature assessing the efficacy of traditional pharmacotherapy in treating AN while also exploring novel treatments, including dissociative anesthetics, psychedelics, cannabinoids, hormones, neurosteroids, and ketogenic nutrition.

Expert opinion: If best practice psychotherapeutic interventions have failed, we recommend a neuroscience and brain research-based medication approach that targets dopamine neurotransmitter receptors to enhance cognitive flexibility and illness insight while reducing dread and avoidance toward food. It is furthermore essential to recognize and treat comorbid conditions such as anxiety, depression, or obsessive-compulsive disorder as they interfere with recovery, and typically do not resolve even with successful AN treatment. Novel strategies have the promise to show efficacy in improving mood and reducing specific AN psychopathology with hopes to be used in clinical practice soon.

Introduction: Erectile dysfunction (ED) is a neglected complication in patients with pre-diabetes or diabetes mellitus (DM).

Areas covered: A summary and review of the role of standard ED treatment and the contribution of lifestyle modification and hypoglycemic drugs.

Expert opinion: Oral phosphodiesterase type 5 inhibitors (PDE5i) represent the first-line therapy even in patients with DM. Testosterone replacement therapy (TRT) is mandatory in all hypogonadal (total testosterone < 12 nmol/l) subjects. Alprostadil and/or combined approaches can be considered when PED5i with or without TRT fail. The glycometabolic optimization through lifestyle modification and the use of hypoglycemic drugs represents a crucial step, even for ED treatment. Considering the strong association between ED and forthcoming cardiovascular diseases, the selection of glucagon-like peptide type 1 analogues or sodium glucose cotransporter-2 inhibitors seems to represent the best option due to their long-term effect on chronic complication prevention. Metformin can be considered a possible alternative in less complicated subjects. Penile prostheses (PP) can be offered when all other options are not effective, but the patients should be informed that poor glycometabolic control can increase the risk of PP infection.

Introduction: Heterotopic ossification (HO), acquired or hereditary, is a diverse pathological condition defined by the production of extraskeletal bone in muscles, soft tissues, and connective tissues. Acquired HO is relatively prevalent and develops mostly in response to trauma, although its etiology is unknown. Genetic forms provide insight into the pathobiological mechanisms of this disorder. Fibrodysplasia ossificans progressiva (FOP) is a rare hereditary form of HO that can have a significant impact on affected individuals. FOP steadily weakens affected subjects and increases their risk of death.

Areas covered: The U.S. Food and Drug Administration has recently approved the retinoid palovarotene as the first compound to treat heterotopic ossification in patients with FOP. This review provides a comprehensive overview of current and potential future pharmacotherapeutic options and their modes of action. The online databases PubMed, Cochrane Library, Web of Science, and ClinicalTrials.gov were searched using the terms 'heterotopic ossification' and 'fibrodysplasia ossificans progressiva' or synonyms, with a special focus over the last 5 years of publications.

Expert opinion: Approval of palovarotene, as the first retinoid indicated for reduction in the volume of new HO, may revolutionize the therapeutic landscape. However, long-term safety and efficacy data for palovarotene are currently lacking.

Introduction: Heart failure (HF) is a global health challenge that requires a multidisciplinary approach. Despite recent advances in pharmacological and interventional therapy, morbidity and mortality in these patients remain high. For this reason, and because of its interplay with other cardiovascular and non-cardiovascular diseases, HF represents a major area of research, with new trials being published every year and international guidelines constantly updated.

Areas covered: The authors review the current status and possible future developments in HF pharmacotherapy.

Expert opinion: The treatment of HF has made significant advances in recent years, and the current recommendations are based on large outcome trials. This has led to significant reductions in both mortality and morbidity, but the death rate remains unacceptably high. In this context, a patient-centered approach that considers comorbidities and specific clinical scenarios when dosing HF medication is essential. Prevention of hospital admissions for cardiac decompensation is of utmost importance in patients with HF as is the enablement of activities of daily living, an endpoint which has only recently been incorporated into major HF trials.

Introduction: Chronic cough has increasingly been recognized as a distinct clinical entity that affects a significant portion of the global population. Despite advancements in understanding its pathophysiology, treatment options remain limited. Opioid analgesics have long been used for cough and some have proven clear antitussive potential. However, these have yet to be approved by regulatory authorities for the treatment of chronic cough. Several novel synthetic opioid modulators that demonstrated antitussive effects in early-stage studies also failed to translate into clinical practice.

Areas covered: This mini review aims to summarize the implications of opioid receptors in the development of cough medicines and highlight recent advances of opioid analgesics in cough trials. PUB MED/CINAHL/Web of Science/Scopus were searched (September 2024).

Expert opinion: Our understanding of the precise sites of action and the involvement of peripheral opioid receptors in cough remains limited. Despite these gaps in knowledge, opioids remain a viable option for some patients until more novel effective treatments are available. Due to the frequent opioid side effects, new opioids derivatives with improved properties are needed. The development of tailored or biased delta-opioid receptor ligands and mixed agonists of opioid receptor-like 1/mu receptors may offer hope for new opioid-based drug discovery for chronic cough.

Introduction: Sepsis remains a major global public health challenge. The host's response in sepsis involves both an exaggerated inflammatory reaction and immunosuppressive mechanisms. A better understanding of this response has shed light on the failure of anti-inflammatory therapies administered under the 'one size fits all' approach during the last decades.

Areas covered: To date, patients' management has moved toward a comprehensive precision medicine approach that aims to personalize immunotherapy, whether anti-inflammatory or immunostimulatory. Large Prospective interventional randomized controlled trials validating this approach are about to start. A crucial prerequisite for these studies is to stratify patients based on biomarkers that will help defining the patients' immuno-inflammatory trajectory.

Expert opinion: Some biomarkers are already available in routine clinical care, while improvements are anticipated through the standardized use of transcriptomics and other multi-omics technologies in this field. With these precautions in mind, it is reasonable to anticipate improvement in outcomes in sepsis.