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Objectives: The objective of this study was to boost pharmacovigilance activity in our psychiatry referral hospital and highlight the pharmacist's role in preventing, detecting, and managing adverse drug reactions (ADRs). Our goal was to promote patient safety and compliance with psychotropic medication by identifying ADR patterns among hospitalized patients in our psychiatry hospital. We aimed to assess and evaluate the causality, severity, and management of documented ADRs along with establishing a hospital-based ADR reporting platform., Methods: We enrolled adult patients (18-60 years) admitted to our psychiatric facility between 1 September 2020 and 30 September 2021 who received at least one psychotropic agent for at least two months. Patients with a history of substance abuse, pregnant females, and patients on clozapine were excluded. Medical records were examined for demographics, clinical details, and psychotropic-related ADRs. ADRs were analyzed for causality using Naranjo's algorithm, for severity using modified Hartwig and Siegel, and for preventability using modified Schumock and Thornton scales., Results: Among 506 admitted patients, 327 suspected psychotropic-related ADRs corresponding to 217 (42.9%) patients, were recorded. Hormonal ADRs were five times higher in men, while the odds of neurological ADRs were significantly higher for women. Otherwise, other ADRs were not statistically affected by gender. Combined therapy was associated with high odds of ADRs, whereas cardiovascular and neurological ADRs were statistically related to monotherapy. Neurological (47.4%) ADRs predominated, followed by cardiovascular (18.7%), and hormonal (15.0%). ADRs were more prevalent among antipsychotics, followed by antidepressants, then mood stabilizers. According to the Naranjo algorithm, some (22.9%) of ADRs were definite, while the majority (74.3%) were probable. As per the Hartwig severity scale, the majority (74.0%) of ADRs were moderate, and the rest (26.0%) were mild. The Modified Schumock and Thornton assessment questionnaire revealed that 75.2% of ADRs were unpreventable, 19.3% were probably preventable, and 5.5% were preventable. In 46.8% of the cases, a new medication was required to manage the emerging ADRs; one-third of ADRs necessitate the replacement of the suspected medication. Close monitoring without any pharmacological intervention was sufficient in 23.2% of cases, while dose reduction was the solution in 7.6% of cases., Conclusions: ADR monitoring in the psychiatry setting by a multidisciplinary team helps recognize the initial signs of ADRs, contributing to better compliance. Hospital-based reporting programs or data-capturing tools will aid in the spontaneous and active assessment of ADRs by healthcare practitioners., (Copyright © 2024, Oman Medical Journal.)

Background: The U.S. Food and Drug Administration (FDA) revised the labels of sodium-glucose transporter 2 (SGLT2) inhibitors in December 2015 to inform users regarding the risk of diabetic ketoacidosis (DKA). As more drugs of this class are approved and their indications are expanded, this serious adverse effect has been increasingly reported., Objective: This review evaluated observational studies to inform the prevalence of SGLT2-inhibitor-associated DKA compared with other antihyperglycemic agents., Methods: A systematic review was conducted in PubMed and EMBASE until 19 July 2022 (PROSPERO: CRD42022385425). We included published retrospective cohort active comparator/new user (ACNU) and prevalent new user studies assessing SGLT2-inhibitor-associated DKA prevalence in adult patients with type 2 diabetes mellitus (T2DM) against active comparators. We excluded studies which lacked 1:1 propensity score matching. The JBI Checklist for Cohort Studies guided the risk-of-bias assessments. Meta-analysis was conducted based on the inverse variance method in R software., Results: Sixteen studies with a sample of 2,956,100 nonunique patients met the inclusion criteria. Most studies were conducted in North America (n = 9) and adopted the ACNU design (n = 15). Meta-analysis of 14 studies identified 33% higher DKA risk associated with SGLT2 inhibitors (HR = 1.33, 95% CI: 1.14-1.55, P < 0.01). Meta-regression analysis identified the study location (P = 0.02), analysis principle (P < 0.001), exclusion of chronic comorbidities (P = 0.007), and canagliflozin (P = 0.04) as significant moderator variables., Conclusions: Despite limitations related to heterogeneity, generalizability, and misclassification, the results of this study show that SGLT2 inhibitors increase the prevalence of DKA among adult T2DM patients in the real world. The findings supplement evidence from randomized controlled trials (RCTs) and call for continued vigilance., Competing Interests: Disclosure The authors declare no conflict of interest., (Copyright © 2023 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Background: The leaves of Gongronema latifolium Benth. have long been recognized traditionally as a remedy for a variety of ailments in Africa. This study was conducted to evaluate the safety profile of the ethanolic extract of G. latifolium (GLES) leaves through a repeated dose 90-day oral toxicity study in male and female of Sprague Dawley rats., Methods: GLES was orally administered at doses of 250, 500 and 1000 mg/kg/day consecutively for 90 days., Results: No behavioral or physiological changes and mortality were observed. GLES did not have a marked impact on general hematological parameters and did not precipitate nephrotoxicity. However, compared to the control, serum triglycerides, total cholesterol and low-density lipoprotein levels were lower and white adipose tissue paired retroperitoneal fat depots were depleted in male rats treated with GLES3 by the end of the experiment. The liver was significantly enlarged in GLES-treated rats of both sexes. Negative gender-specific alterations were observed with the highest dose. Adverse risk was evident in the female rats mainly due to marked body weight gain and cerebrum weight reduction., Conclusion: Further research is needed to reach more specific conclusions about to the safety of ingesting high doses of GLES for long periods of time.

Background: An aqueous extract (AE) of vinegar made from Nypa fruticans Wurmb. can improve postprandial glucose levels in normoglycaemic rats. The aim of this study was to evaluate its antihyperglycaemic activity further using in vivo and in vitro approaches., Methods: AE was administered to streptozotocin (STZ)-induced diabetic rats twice daily at three doses (1000, 500, and 250 mg/kg b.w.) for 12 days p.o. Several biochemical analyses and a histological study of the pancreas and liver were performed, accompanied by a cell culture assay., Results: As compared to diabetic control (DC), AE at the doses of 500 and 1000 mg/kg b.w. caused significant reduction ( p < 0.05) of blood glucose, total cholesterol and triglycerides levels, with positive improvement of serum insulin levels. Interestingly, immunohistochemical staining of the pancreas suggested no β-cell regeneration, despite significant increase in insulin production. AE-treated groups, however, showed overall restoration of the hepatic histoarchitecture of STZ-induced liver damage, suggesting a possible hepatoprotective effect. The pancreatic effect of AE was further studied through RIN-5F cell culture, which revealed a positive stimulatory effect on insulin release at a basal glucose concentration (1.1 mM)., Conclusion: Nypa fruticans Wurmb. vinegar's aqueous extract exerts its antihyperglycaemic activity, at least in part, through insulin stimulatory and hepatoprotective effects., Competing Interests: The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

Context: Clinacanthus nutans (CN) is used traditionally for treating various illnesses. Robust safety data to support its use is lacking., Objective: To evaluate the adverse effects of aqueous extract of CN leaves (AECNL)., Materials and Methods: The oral toxicity of the AECNL was tested following Organisation for Economic Co-operation and Development (OECD) guidelines. Mutagenicity (Ames test) of AECNL was evaluated using TA98 and TA100 Salmonella typhimurium strains., Results: No mortality or morbidity was found in the animals upon single and repeated dose administration. However, significant body weight loss was observed at 2000 mg/kg during sub-chronic (90 d) exposure. In addition, increased eosinophil at 500 mg/kg and decreased serum alkaline phosphatase levels at 2000 mg/kg were observed in male rats. Variations in glucose and lipid profiles in treated groups were also observed compared to control. Ames test revealed no evidence of mutagenic or carcinogenic effects at 500 μg/well of AECNL., Conclusion: The median lethal dose (LD50) of the AECNL is >5000 mg/kg and the no-observed-adverse-effect level is identified to be greater than 2000 mg/kg/day in 90-d study.

Background: Gongronema latifolium Benth. (GL) possesses considerable glucose lowering effects able to be utilized on a large-scale. This paper investigates the effects of a Soxhlet extract on hyperglycemia, Langerhans islets and glucose uptake by abdominal muscles., Methods: Ethanol and a Soxhlet apparatus were used to obtain GL ethanolic Soxhlet extract (GLES). It was then administered to randomly-segregated male Sprague-Dawley , normal and STZ-induced diabetic rats, using oral gavage to evaluate blood glucose levels (BGLs), serum lipid profile, insulin levels and the pancreas post-treatment., Results: GLES significantly ( p < 0.05) decreased BGLs of normal rats in glucose tolerance testing at a dose of 2 g/kg b.w. but failed to do so in diabetic rats undergoing acute 7-h treatment. Given twice-daily, 1 g/kg b.w. of GLES moderately controlled diabetic BGLs starting from day 10. After 14 days of treatment, 1 g/kg and 0.5 g/kg b.w. of GLES caused 44% and 50% respective increases in the average area of Langerhans islets compared to DC. Using isolated rat abdominal muscle, GLES was found to be a mild insulin-sensitizer. GC-MS analysis revealed the presence of the known glucose-lowering phytosterol, Sitostenone., Conclusion: Despite retaining moderate antidiabetic activity, Soxhlet extraction of Gongronema latifolium probably leads to the destruction of active heat-liable compounds.

Alstonia scholaris has been used by traditional medicine practitioners since the medieval ages for the treatment of diseases. The aim of this research was to evaluate the acute and sub-acute oral toxicity of its methanolic extract. The acute toxicity test was conducted using Sprague Dawley (SD) rats. The methanolic extract of Alstonia scholaris stem bark (ASME) was administrated in a single dose of 2000 mg/kg via oral gavage; and the animals were observed for any behavioral changes or mortality. In the sub-acute toxicity study, SD rats received three doses of ASME (250, 500 and 1000 mg/kg) for 28 days via oral gavage. During these 28 days of treatment, the rats were observed weekly for toxicity symptoms. Following the 28-day treatment, the rats were sacrificed for hematological, biochemical and histopathology studies. In the acute toxicity study, Alstonia scholaris was found to be non-toxic at a dose of 2000 mg/kg b.w. In the sub-acute toxicity study, significant variations in body weight, hematological and biochemical parameters were observed in the experimental groups at the dose of 500 and 1000 mg/kg with the death of two female rats being recorded at the highest dose (1000 mg/kg b.w.). Histopathological studies revealed slight degeneration (lesion) and centrilobular necrosis in the liver, which was most expressed in the highest-dose group. These results demonstrate that, while a single dose and short term oral intake of Alstonia scholaris bark extract caused no toxicity up to a dose of 2000 mg/kg b.w., toxic effects manifested in the long term treatment at the highest dose (500 and 1000 mg/kg). The long-term toxic effect was found to be associated with alterations in hematological compositions and end-organ damage to the liver. Thus, prolonged use of high doses of ASME orally should be discouraged and lower doses encouraged.

Nypa fruticans Wurmb. vinegar, commonly known as nipa palm vinegar (NPV) has been used as a folklore medicine among the Malay community to treat diabetes. Early work has shown that aqueous extract (AE) of NPV exerts a potent antihyperglycemic effect. Thus, this study is conducted to evaluate the effect of AE on postprandial hyperglycemia in an attempt to understand its mechanism of antidiabetic action. AE were tested via in vitro intestinal glucose absorption, in vivo carbohydrate tolerance tests and spectrophotometric enzyme inhibition assays. One mg/mL of AE showed a comparable outcome to the use of phloridzin (1 mM) in vitro as it delayed glucose absorption through isolated rat jejunum more effectively than acarbose (1 mg/mL). Further in vivo confirmatory tests showed AE (500 mg/kg) to cause a significant suppression in postprandial hyperglycemia 30 min following respective glucose (2 g/kg), sucrose (4 g/kg) and starch (3 g/kg) loadings in normal rats, compared to the control group. Conversely, in spectrophotometric enzymatic assays, AE showed rather a weak inhibitory activity against both α-glucosidase and α-amylase when compared with acarbose. The findings suggested that NPV exerts its anti-diabetic effect by delaying carbohydrate absorption from the small intestine through selective inhibition of intestinal glucose transporters, therefore suppressing postprandial hyperglycemia.