Current Reviews in Clinical and Experimental Pharmacology - Volume 17, Issue 3, 2022

Background: Functional gastrointestinal disorders account for at least a third of visits to gastroenterology clinics. Despite pathophysiological complexity, impaired gut motility may be frequently present in these disorders. Introduction: Prokinetics are a class of drugs that promote gastrointestinal motility, accelerate transit, and potentially improve digestive symptoms. Several prokinetic agents with a great variety of mechanisms of action are available. Aim: The purpose of this paper is to update our current knowledge about the efficacy and safety of prokinetics. Methods: A literature search on efficacy and safety of prokinetics was carried out using the online databases of Pubmed, Medline, and Cochrane. Results: Based on the action of different receptors, prokinetics mainly comprise dopamine antagonists, 5HT4 agonists, motilin agonists, ghrelin agonists, and cholinergic agonists. Prokinetics have the potential to improve motility function in all segments of the digestive tract, from the esophagus to the colon. In particular, drug international agencies have approved antidopaminergic metoclopramide for the treatment of gastroparesis and serotoninergic prucalopride for chronic constipation not responsive to traditional laxatives. Arrhythmias by QT prolongation and galactorrhea by prolactin stimulation are the more frequent side effects related to prokinetics use. Conclusion: Old and new prokinetics are effective in ameliorating digestive motility disorders and related symptoms and are widely prescribed. Special attention should be paid to the potential adverse events of these agents.

Background: Autism Spectrum Disorders (ASDs) are a group of prevalent neuropsychiatric disorders. They present a complex and unknown etiology, which in most cases includes significant peripheral alterations outside the brain such as in the composition of gut microbiota. Because the gut microbiota is involved in modulating the gut-brain axis, several studies have suggested that the microbiome in the gut can modify metabolites which are able to cross the blood-brain barrier and modulate brain function. Methods: We reviewed the current evidence regarding microbiota alterations in patients with ASD and the effects of the administration of probiotics and prebiotics in these patients, both in terms of gastrointestinal and behavioural symptoms. Results: Administration of a probiotic formulation containing different strains of Lactobacillus (L. acidophilus, L. rhamnosus, and others) and Bifidobacteria had beneficial effects upon these aforementioned symptoms and their use is recommended in a subgroup of ASD patients that present gastrointestinal disturbances. Nonetheless, the types of gastrointestinal disturbances that most benefit from such interventions remain to be elucidated in order to personalize the medical approaches. Conclusion: Recent clinical studies have shown that probiotic treatments can regulate the gut microbiota and may result in improvements in some behavioral abnormalities associated with ASD. Trials using prebiotic fibers or synbiotics preparations are still lacking and necessary in order to deep in such therapeutic strategies in ASD with comorbid gastrointestinal disrturbances.

PI3K/AKT/mTOR (phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin) signaling pathway is an important signal transduction pathway mediated by enzyme-linked receptors with many biological functions in mammals. This pathway modulates the epigenetic modification of DNA and target gene histones and plays a significant role in regulating biological activity, disease progression, oncogenesis, and cancer progression. PI3K/AKT/mTOR signaling pathway involves and mediates many cellular processes such as nutrient uptake, proliferation, anabolic reactions, and cell survival. Several studies have shown that PI3K/AKT/mTOR has been a promising therapeutic approach to intracerebral hemorrhage (ICH). ICH is characterized by the progressive development of hematoma, which leads to the structural destabilization of the neurons and glial cells, leading to neuronal deformation, further contributing to mitochondrial dysfunction, membrane depolarization, oligaemia, and neurotransmitter imbalance. Partial suppression of cell metabolism and necrosis can occur, depending on the degree of mitochondrial dysfunction. Therefore in the following review, we discuss whether or not the activation of the PI3K/AKT/mTOR signaling pathway could minimize neuronal dysfunction following ICH. We further elaborate the review by discussing the updated pathophysiology of brain hemorrhage and the role of molecular targets in other neurodegenerative diseases. This review provides current approachable disease treatment in various disease states, single and dual PI3K/AKT/mTOR signaling pathway modulators.

Background: Treatment with N-Acetyl Cysteine (NAC) in rodenticide poisoning has not been well established due to mixed study results and insufficient evidence. This review aimed to summarize the clinical benefits of NAC in the management of rodenticide poisoning. Methods: This review follows the PICOS framework and the PRISMA guidelines. Pub- Med/MEDLINE, Scopus, and the Cochrane library were searched to identify the published literature from inception to September 2020, and a reference search was performed for additional relevant studies. The English language studies addressing the use of NAC in rodenticide poisoning were considered for the review. We considered all experimental and observational studies due to the insufficient number of interventional studies. Results: Ten studies (two RCTs, four observational, and four descriptive) out of 2,178 studies with 492 participants were considered for the review. Only six studies (two RCTs, one prospective, and three retrospective studies) reported recovery and mortality. Pooled results of RCTs (n=2) showed a significant recovery rate (Odds Ratio [OR]: 3.97; 95% Confidence Interval [CI]:1.69-9.30), whereas summary estimates of prospective and retrospective studies recorded a non-significant effect. Metaanalysis of RCTs (OR: 0.25; 95% CI: 0.11-0.59; n=2) and retrospective studies (OR: 0.34; 95% CI: 0.15-0.78; n=3) showed a significant reduction in mortality, whereas pooled analysis of prospective studies recorded a non-significant effect. A significant reduction in intubation or ventilation (OR: 0.25; 95% CI: 0.11-0.60; 2 RCTs) and a non-significant (P=0.41) difference in duration of hospitalization was observed with NAC when compared to the non-NAC treated group. The quality of the included studies appeared to be moderate to high. Conclusion: Our findings indicate that NAC showed better survival and lower mortality rate when compared to non-NAC treated group; hence NAC can be considered for the management of rodenticide poisoning.

Background: Respiratory tract infections are a primary cause of illness and mortality over the world. Objective : This study was aimed to investigate the effectiveness of vitamin C supplementation in preventing and treating respiratory tract infections. Methods: We used the Cochrane, PubMed, and MEDLINE Ovid databases to conduct our search. The inclusion criteria were placebo-controlled trials. Random effects meta-analyses were performed to measure the pooled effects of vitamin C supplementation on the incidence, severity, and duration of respiratory illness. Results : We found ten studies that met our inclusion criteria out of a total of 2758. The pooled risk ratio (RR) of developing respiratory illness when taking vitamin C regularly across the study period was 0.94 (with a 95% confidence interval of 0.87 to 1.01) which found that supplementing with vitamin C lowers the occurrence of illness. This effect, however, was statistically insignificant (P= 0.09). This study showed that vitamin C supplementation had no consistent effect on the severity of respiratory illness (SMD 0.14, 95% CI -0.02 to 0.30: I2 = 22%, P=0.09). However, our study revealed that vitamin C group had a considerably shorter duration of respiratory infection (SMD -0.36, 95% CI -0.62 to -0.09, P = 0.01). Conclusion: Benefits of normal vitamin C supplementation for reducing the duration of respiratory tract illness were supported by our meta-analysis findings. Since few trials have examined the effects of therapeutic supplementation, further research is needed in this area.

Introduction: Hydroxychloroquine (HCQ) has recently become the focus of attention in the current COVID-19 pandemic. With an increase in the off-label use of HCQ, concern for the safety of HCQ has been raised. We, therefore, performed this systematic review to analyze the safety data of HCQ against placebo and active treatment in various disease conditions. Methods: We searched PubMed, Embase, and Cochrane for Randomized Controlled Trials (RCTs) and Observational Studies (OSs) that evaluated HCQ for the treatment of any disease other than COVID19 in adult patients up to May 2020. We assessed the quality of the included studies using Risk of Bias 2 (for RCTs) and Newcastle–Ottawa Scale (for OSs). Data were analyzed with randomeffect meta-analysis. Sensitivity and subgroup analyses were performed to identify heterogeneity. Results: A total of 6641 studies were screened, and 49 studies (40 RCTs and 9 OSs) with a total sample size of 35044 patients were included. The use of HCQ was associated with higher risks of TDAEs as compared to placebo/no active treatment [RR 1.47, 95%CI 1.03-2.08]. When HCQ was compared with active treatments, the risks of AEs [RR 0.74, 95% CI 0.63-0.86] and TDAEs were less in the HCQ arm [RR 0.57, 95% CI 0.39-0.81]. The outcomes did not differ in the sensitivity analysis. Conclusion: The results suggest that the use of HCQ was associated with a lower risk of AEs and TDAEs as compared to active treatment, whereas posing higher risk of TDAEs as compared to placebo.