Current Reviews in Clinical and Experimental Pharmacology - Volume 19, Issue 3, 2024

Background: Individuals at higher altitudes may experience a decrease in blood oxygen levels, which can result in a variety of clinical illnesses, such as high-altitude pulmonary edema, high-altitude cerebral edema, and milder but more common acute mountain sickness (AMS). Objective: This study aims to review the current state of knowledge related to motion sickness, the risk of AMS, and pharmacological and non-pharmacological treatments for AMS. Methods: Several databases, including PubMed, Bentham Science, Elsevier, Springer, and Research Gate, were used to compile the data for the article following a thorough analysis of the various research findings connected to acute mountain sickness and motion sickness, along with treatments and prevention. Results: This article covers the research on mountain sickness as well as every imaginable form of conventional and alternative medicine. It contains ten medicinal plants that are useful in treating mountain sickness and various other remedies. Additionally, case studies are provided. Conclusion: Therefore, the information in the paper will help travel medicine specialists better personalize their appropriate care for patients who travel to high-altitude locations. Additionally, all available antiemetic medications, serotonin agonists, nonsteroidal anti-inflammatory drugs, and herbal treatments for motion sickness were discussed. The prevention and consequences of acute mountain sickness are also covered in this study.

Farnesoid X receptor (FXR) was identified as an orphan nuclear receptor resembling the steroid receptor in the late ’90s. Activation of FXR is a crucial step in many physiological functions of the liver. A vital role of FXR is impacting the amount of bile acids in the hepatocytes, which it performs by reducing bile acid synthesis, stimulating the bile salt export pump, and inhibiting its enterohepatic circulation, thus protecting the hepatocytes against the toxic accumulation of bile acids. Furthermore, FXR mediates bile acid biotransformation in the intestine, liver regeneration, glucose hemostasis, and lipid metabolism. In this review, we first discuss the mechanisms of the disparate pleiotropic actions of FXR agonists. We then delve into the pharmacokinetics of Obeticholic acid (OCA), the first-in-class selective, potent FXR agonist. We additionally discuss the clinical journey of OCA in humans, its current evidence in various human diseases, and its plausible roles in the future.

Inflammatory bowel disease (IBD), represented by Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disorder of the gastrointestinal tract (GIT) characterized by chronic relapsing intestinal inflammation, abdominal pain, cramping, loss of appetite, fatigue, diarrhoea, and weight loss. Although the etiology of IBD remains unclear, it is believed to be an interaction between genes, and environmental factors, such as an imbalance of the intestinal microbiota, changing food habits, an ultra-hygiene environment, and an inappropriate immune system. The development of novel effective therapies is stymied by a lack of understanding of the aetiology of IBD. The current therapy involves the use of aminosalicylates, immunosuppressants, and corticosteroids that can effectively manage symptoms, induce and sustain remission, prevent complications, modify the course of the disease, provide diverse treatment options, showcase advancements in biologic therapies, and enhance the overall quality of life. However, the efficacy of current therapy is overshadowed by a plethora of adverse effects, such as loss of weight, mood swings, skin issues, loss of bone density, higher vulnerability to infections, and elevated blood pressure. Biologicals, like anti-tumour necrosis factor agents, can stimulate an autoimmune response in certain individuals that may diminish the effectiveness of the medication over time, necessitating a switch to alternative treatments. The response of IBD patients to current drug therapy is quite varied, which can lead to disease flares that underlines the urgent need to explore alternative treatment option to address the unmet need of developing new treatment strategies for IBD with high efficacy and fewer adverse effects. Drug repurposing is a novel strategy where existing drugs that have already been validated safe in patients for the management of certain diseases are redeployed to treat other, unindicated diseases. The present narrative review focuses on potential drug candidates that could be repurposed for the management of IBD using on-target and off-target strategies. It covers their preclinical, clinical assessment, mechanism of action, and safety profiles, and forecasts their appropriateness in the management of IBD. The review presents useful insights into the most promising candidates for repurposing, like anti-inflammatory and anti-apoptotic troxerutin, which has been found to improve the DSS-induced colitis in rats, an antiosteoarthritic drug diacetylrhein that has been found to have remarkable ameliorating effects on DSS-induced colitis via anti-oxidant and anti- inflammatory properties and by influencing both apoptosis and pyroptosis. Topiramate, an antiepileptic and anticonvulsant drug, has remarkably decreased overall pathophysiological and histopathological events in the experimental model of IBD in rodents by its cytokine inhibitory action.

Fungal infections are emerging as major health challenges in recent years. The development of resistance against existing antifungal agents needs urgent attention and action. The limited classes of antifungal drugs available, their tendency to cause adverse effects, lack of effectiveness, etc., are the major limitations of current therapy. Thus, there is a pressing demand for new antifungal drug classes to cope with the present circumstances. Glucose is the key source of energy for all organisms, including fungi. Glucose plays a crucial role as a source of carbon and energy for processes like virulence, growth, invasion, biofilm formation, and resistance development. The glucose transport and sensing mechanisms are well developed in these organisms as an important strategy to sustain survival. Modulating these transport or sensor mechanisms may serve as an important strategy to inhibit fungal growth. Moreover, the structural difference between human and fungal glucose transporters makes them more appealing as drug targets. Limited literature is available for fungal glucose entry mechanisms. This review provides a comprehensive account of sugar transport mechanisms in common fungal pathogens.

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.

Background: A substantial number of research studies on metronidazole-related cutaneous symptoms have recently been published. Our objective was to identify and evaluate descriptive studies that described metronidazole-related skin manifestations, therapeutic interventions, and consequences. Methods: A comprehensive literature search was carried out in the PubMed, Scopus, and grey literature databases from inception to April 2022 without any constraints, as well as a snowball search in Google and a search in Google Scholar. Descriptive articles describing metronidazole-related cutaneous manifestations were considered for the review. Two distinct reviewers carried out the research selection, data extraction, and quality assessment; any discrepancies were resolved by consensus with the third reviewer. Results: About 24 out of 4648 descriptive studies, including 26 patients (20 Female patients and 6 male patients), were included in this review. The included studies comprised a range of ages from 16 to 78 years old. Metronidazole was indicated for the treatment of bacterial vaginosis, trichomoniasis, sepsis, anti-infection therapy, perforated appendicitis, rosacea, vaginal discharge, dysentery, acne rosacea, trichomonal vaginitis, lichen planus, liver abscess, facial rosacea, intestinal amoebiasis, and gingivitis. Fixed drug eruption was the most common skin manifestation which was reported in 7 cases included in this review. Cutaneous manifestations were ameliorated by cessation of the offending drug and by apportioning antihistamines, topical steroids, parenteral corticosteroids, emollients, and topical moisturizers. Conclusion: Clinicians and healthcare professionals should be cognizant of the potential cutaneous adverse drug reactions (CADRs) induced by metronidazole to mitigate fatal circumstances. The management of the CADRs appears to respond effectively with immediate drug discontinuation and supportive therapy.

Aim: This research aimed to examine the relationship between the intake of statins and the risk of post-stroke pneumonia in a systematic review and meta-analysis study. Methods: An extensive search of published articles on March 2^1st, 2023, was done in several databases, like Web of Science (ISI), PubMed, Cochrane Library, Embase, Scopus, and Google Scholar. The Newcastle Ottawa Scale (NOS) checklist was employed to evaluate the quality of observational studies. Statistical tests (Chi-square test and I²) and graphical techniques (Forest plot) were used to determine whether heterogeneity existed in the meta-analysis studies. Funnel plots and Begg and Egger's tests were used to assess the publication bias. Results: Seven studies (5 cohort and 2 case-control studies) were retrieved to examine the association between statins and post-stroke pneumonia. The sample size of the studies compiled in the meta- analysis was obtained to be 68,966 participants. Meta-analysis demonstrated that the overall odds of post-stroke pneumonia in the statin group was equal to 0.87 (95% CI: 0.67 – 1.13; p-value 0.458). Subgroup analysis indicated that the odds of post-stroke pneumonia in the statin group was equal to 0.93 (95% CI: 0.73-1.18; p-value = 0.558) in the cohort studies, and equal to 0.92 (95% CI: 0.37-2.26; p-value = 0.857) in the case-control studies. The examination of the association between the intake of statins and post-stroke pneumonia showed no evidence of publication bias (Begg's test, p-value = 0.368; Eggers test, p-value = 0.282). Conclusion: In this study, no relationship has been observed between receiving statins and the risk of post-stroke pneumonia.