Current Reviews in Clinical and Experimental Pharmacology最新文献

Background: Bigles are novel formulation merging two phase of hydrogel and organogel revealing dual properties to release active agents based on their lipophilic or hydrophilic nature.

Methods: A systematic search was conducted in PubMed, Scopus, and ISI Web of Science to find eligible studies evaluating the efficiency of bigels in drug release. 20 articles were included in the analysis based on the defined criteria.

Results: The results indicated that several different natural materials were used for bigel making. Span (52.38%) and Sunflower oil (23.80%) were the most solvents used for organogel formation. Also, gelatin, agar, gums, and other types of biopolymer were used as hydroglators. Most research (33.33%) focused on the release of metronidazole from bigel structure. Also, the range of drug release rates was 1.59 - 100% and in 42.85% of studies was >90%. The nature, content, and properties of both organogel and hydrogel and some process variables such as temperature, mixing speed and storage conditions were highlighted as the main influential factors on bigel formation and its bioactivity.

Conclusion: Bigels are an innovative structure that provides desired physicochemical and rheological properties for industrial applications. Excellent biocompatibility and in vitro / ex vivo results have been documented for developed bigels. In this regard, an optimal preparation method is very important to show superior therapeutic effects.

Background: All vitiligo treatments are restricted, and no known treatment reliably produces repigmentation. In this study, we investigated the efficacy and safety of 5-Fluorouracil (5FU) as adjuvant therapy in treating vitiligo.

Method: Using five significant databases, an electronic systematic search of the literature was conducted. Randomized Clinical Trials (RCTs) that investigated 5FU for treating vitiligo in humans were selected for a meta-analysis and systematic review. This study was conducted by following PROSPERO (CRD42022345736).

Results: A total of 10 studies involving 302 patients were included in our systematic review. The meta-analysis of eight studies revealed that the combination of 5FU with microneedling showed a statistically significant superior effect in comparison with other treatment modalities in ing >75% repigmentation (OR= 4.47; 95%CI= (2.39, 8.35), P < 0.00001). 5FU with microneedling versus microneedling alone showed higher efficacy of 5FU with statistically significant results (OR= 4.22; 95%CI= (1.55, 11.44), P= 0.005). Regarding the influence of different formulations of 5FU, the meta-regression revealed that the highest efficacy was achieved when microneedling was combined with liposomal formulations. There were not any reported severe side effects related to 5FU.

Conclusion: 5FU as an adjuvant treatment for vitiligo was found to be more effective in achieving ≥75% repigmentation rates.

Background: This review investigates the efficacy of deutetrabenazine in the management of chorea related to HD. Motor, psychological, and cognitive symptoms characterize HD, a neurodegenerative disease. One prominent movement disorder associated with HD is chorea, which results in uncontrollably jerky movements of the muscles. HD has no known cure; instead, symptom management with a variety of medication options is the main goal. Effective management is essential because chorea has a significant impact on patients' quality of life. Dutetrabenazine is the first deuterated medication to receive approval from the US Food and Drug Administration (FDA) for the therapeutic treatment of chorea in Huntington's disease (HD).

Objectives: Treating chorea associated with HD may benefit from the use of deutetrabenazine. The novel compound deutetrabenazine contains deuterium. It inhibits CYP2D6 metabolism, prolongs the half-lives of active metabolites, and may cause persistent systemic exposure while maintaining significant pharmacological action. Deutetrabenazine decreases the release of monoamines, including dopamine, in the synaptic cleft by inhibiting the VMAT2 vesicular monoamine transporter. For chorea, this mechanism has a therapeutic effect. For the treatment of choreiform movement and tardive dyskinesia in HD, the FDA approved deutetrabenazine in 2017.

Conclusion: Here we highlight, Deutetrabenazine as a promising new treatment for Huntington's disease chorea, for patients with chorea, deutetrabenazine offers hope for an enhanced quality of life. To completely understand its effectiveness and potential advantages, additional research is necessary, including direct comparison studies, as a result of the mixed study results.

Cancer is a high-morbidity disease prevalent worldwide. Chemotherapy is the primarily used regimen for cancer treatment; however, it also brings severe side effects. Chemotherapy-induced Peripheral Neuropathy (CIPN) and Chemotherapy-induced Cognitive Impairment (CICI) are two main complications occurring in chemotherapy. They are both associated with nervous system injury and are therefore collectively referred to as Chemotherapy-induced Neuropathy (CIN). CIPN induces neuralgia and numbness in limbs, while CICI causes amnesia and cognitive dysfunction. Currently, there are no effective therapeutics to prevent or cure CIN, so research into new drugs to alleviate CIN becomes urgent. Oxidative stress and neuroinflammation are the common pathogenic mechanisms of CIPN and CICI. Excessive Reactive Oxygen Species (ROS) and pro-inflammatory cytokines cause peripheral nervous system damage and hence CIPN. Peripheral ROS and cytokines also change the permeability of the blood-brain barrier, thereby increasing oxidative stress and neuroinflammation in the central nervous system, ultimately leading to CICI. Several antidepressants have been used to treat CIN and exhibited good clinical effects. Their potential pharmacological mechanism has been reported to ameliorate oxidative stress and neuroinflammation, guiding a new feasible way for effective therapeutic development against CIN. This mini-review has summarized the latest advances in the research on CIN with respect to clinical status, pathogenesis, and treatment. It has also discussed the potential of repurposing antidepressants for CIN treatment and prospected the strategy of developing therapeutics by targeting oxidative stress and neuroinflammation against CIN.

Predictions are made by artificial intelligence, especially through machine learning, which uses algorithms and past knowledge. Notably, there has been an increase in interest in using artificial intelligence, particularly generative AI, in the pharmacovigilance of pharmaceuticals under development, as well as those already in the market. This review was conducted to understand how generative AI can play an important role in pharmacovigilance and improving drug safety monitoring. Data from previously published articles and news items were reviewed in order to obtain information. We used PubMed and Google Scholar as our search engines, and keywords (pharmacovigilance, artificial intelligence, machine learning, drug safety, and patient safety) were used. In toto, we reviewed 109 articles published till 31 January 2024, and the obtained information was interpreted, compiled, evaluated, and conclusions were reached. Generative AI has transformative potential in pharmacovigilance, showcasing benefits, such as enhanced adverse event detection, data-driven risk prediction, and optimized drug development. By making it easier to process and analyze big datasets, generative artificial intelligence has applications across a variety of disease states. Machine learning and automation in this field can streamline pharmacovigilance procedures and provide a more efficient way to assess safety-related data. Nevertheless, more investigation is required to determine how this optimization affects the caliber of safety analyses. In the near future, the increased utilization of artificial intelligence is anticipated, especially in predicting side effects and Adverse Drug Reactions (ADRs).

Current therapeutic approaches for Huntington's disease (HD) focus on symptomatic treatment. Therefore, the unavailability of efficient disease-modifying medicines is a significant challenge. Regarding the molecular etiology, targeting the mutant gene or advanced translational steps could be considered promising strategies. The evidence in gene therapy suggests various molecular techniques, including knocking down mHTT expression using antisense oligonucleotides and small interfering RNAs and gene editing with zinc finger proteins and CRISPR-Cas9-based techniques. Several post-transcriptional and post-translational modifications have also been proposed. However, the efficacy and long-term side effects of these modalities have yet to be verified. Currently, cell therapy can be employed in combination with conventional treatment and could be used for HD in which the structural and functional restoration of degenerated neurons can occur. Several animal models have been established recently to develop cell-based therapies using renewable cell sources such as embryonic stem cells, induced pluripotent stem cells, mesenchymal stromal cells, and neural stem cells. These models face numerous challenges in translation into clinics. Nevertheless, investigations in Advanced Therapy Medicinal Products (ATMPs) open a promising window for HD research and their clinical application. In this study, the ATMPs entry pathway in HD management was highlighted, and their advantages and disadvantages were discussed.

Objective: There is a lack of evidence on the effectiveness of antidotes in the management of organophosphate and carbamate (OPC) poisoning. We aimed to review the efficacy and safety of glycopyrrolate in the management of OPC poisoning.

Methodology: Databases such as PubMed, Scopus, Embase, and Cochrane Library were extensively searched from inception to November 2022 and updated till October 2023. Interventional, observational, and descriptive studies assessing the efficacy and safety of glycopyrrolate administered in any dose, route, and duration for the management of OPC poisoning published in the English language were considered for this review. The treatment with any other regimen that did not include glycopyrrolate was regarded as the comparator. The survival, intensive care unit (ICU) days and ventilatory outcomes were considered efficacy outcomes, and adverse effects were considered safety outcomes. Suitable quality assessment tools were used to assess the risk of bias in the included studies. Two independent reviewers were involved in the study selection, data extraction, and quality assessment and any discrepancies were resolved through mutual discussion or consultation with a third reviewer.

Results: A total of 9 studies (2 RCTs, 4 cohorts, 1 case series, and 2 case reports) out of 591 nonduplicate records were considered for this review. Overall, the RCTs were observed to have a moderate quality, and observational studies and descriptive studies were found to have good quality. All the included studies used atropine administration as a standard treatment option along with glycopyrrolate. The OPC patients treated with glycopyrrolate had a fewer hospitalization days with comparable recovery and ventilatory outcomes than those that had not been treated with glycopyrrolate. The occurrence of adverse events and complications was lower in the glycopyrrolate group than in the control group.

Conclusion: Currently, there is a lack of comparative studies to recommend the use of glycopyrrolate in OPC poisoning, and further interventional studies are required to make an evidencebased recommendation on this topic.

Natural products have historically driven pharmaceutical discovery, but their reliance has diminished with synthetic drugs. Approximately 35% of medicines originate from natural products. Scopoletin, a natural coumarin compound found in herbs, exhibits antioxidant, hepatoprotective, antiviral, and antimicrobial properties through diverse intracellular signaling mechanisms. Furthermore, it also enhances the activity of antioxidants. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes viral pneumonia through cytokine storms and systemic inflammation. Cellular autophagy pathways play a role in coronavirus replication and inflammation. The Silent Information Regulator 1 (SIRT1) pathway, linked to autophagy, protects cells via FOXO3, inhibits apoptosis, and modulates SIRT1 in type-II epithelial cells. SIRT1 activation by adenosine monophosphate-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) enhances the autophagy cascade. This pathway holds therapeutic potential for alveolar and pulmonary diseases and is crucial in lung inflammation. Angiotensin-converting enzyme 2 (ACE-2) activation, inhibited by reduced expression, prevents COVID-19 virus entry into type-II epithelial cells. The coronavirus disease 2019 (COVID-19) virus binds ACE-2 to enter into the host cells, and XBB.1.5 COVID-19 displays high ACE-2-binding affinity. ACE-2 expression in pneumocytes is regulated by signal transducers and activators of transcription-3 (STAT3), which can increase COVID-19 virus replication. SIRT1 regulates STAT3, and the SIRT1/STAT3 pathway is involved in lung diseases. Therapeutic regulation of SIRT1 protects the lungs from inflammation caused by viral-mediated oxidative stress. Scopoletin, as a modulator of the SIRT1 cascade, can regulate autophagy and inhibit the entry and life cycle of XBB.1.5 COVID-19 in host cells.

Objective: Pharmacotherapy is commonly used during quit attempts and has shown an increase in the likelihood of achieving abstinence. However, with established pharmacotherapies, abstinence rates following a quit attempt remain low, and relapse is common. This review aims to investigate the efficacy and harm profiles of current and emerging pharmacotherapies.

Methods: Literature review of current and emerging pharmacotherapies for smoking cessation and tobacco use disorder.

Results: Emerging pharmacotherapies include new formulations of existing therapies, drug repurposing and some new treatments. New treatments are welcome and may incorporate different mechanisms of action or different safety and tolerability profiles compared to existing treatments. However, emerging pharmacotherapies have yet to demonstrate greater efficacy compared to existing treatments. The emergence of Electronic Nicotine Delivery Systems (ENDS) or 'vaping' is a feature of the current debate around tobacco use disorder. ENDS appear to facilitate switching but not quitting and are controversial as a harm minimisation strategy.

Limitations: Studies included a broad range of therapies and trial designs that should be compared with their differences taken into consideration.

Conclusion: Strategies to successfully quit smoking vary between individuals and may extend beyond pharmacotherapy and involve complex psychosocial factors and pathways.