J Allergy Clin Immunol Pract. 2022 Oct;10(10):2772-2773. doi: 10.1016/j.jaip.2022.07.023.

NO ABSTRACT

PMID:36216464 | DOI:10.1016/j.jaip.2022.07.023

Pathol Oncol Res. 2022 Sep 23;28:1610694. doi: 10.3389/pore.2022.1610694. eCollection 2022.

ABSTRACT

The concept of precision medicine is based on the identification of hallmarks of cancer to exploit them as drug targets. The basic idea was that in this way the therapeutic modalities will be more effective and the side effects will be less. Since the majority of these novel modalities are not specific for a cancer-related biological process or a cancer-specific (mutant) target protein, it is not a surprise that we had to learn new type of side effects, because these therapeutics also affect physiological or pathological processes. Even more, in cases of some of these novel therapies we were able to discover new molecular mechanisms of physiological and pathological processes. Identification of the on-target side effects of targeted drugs can help to prevent the development of them or better manage the patients when emerge during cancer therapy.

PMID:36213163 | PMC:PMC9537356 | DOI:10.3389/pore.2022.1610694

J Acquir Immune Defic Syndr. 2022 Oct 10. doi: 10.1097/QAI.0000000000003116. Online ahead of print.

ABSTRACT

BACKGROUND: We studied the pharmacokinetics (PK) and safety of 100mg doravirine and doravirine/lamivudine/tenofovir disoproxil fumarate fixed dose combination (100/300/300mg- DOR FDC) treatment in adolescents with HIV-1.

METHODS: Adolescents ages 12- <18 years enrolled in two sequential cohorts. Cohort 1 evaluated intensive PK and short-term safety of 100mg single-dose doravirine in adolescents ≥ 35 kg. Cohort 2 participants either initiated treatment with DOR FDC (antiretroviral (ARV)-naïve) or switched to DOR FDC from a previous ARV regimen (virologically-suppressed). The first 10 Cohort 2 participants had intensive PK evaluations, and safety, sparse PK and HIV RNA were assessed through week 24.

RESULTS: Fifty-five adolescents, median age 15.0 years and baseline weight 51.5 kg, enrolled. Nine participants completed Cohort 1 PK assessments (8 of the 9 participants weighed ≥45 kg) and 45 initiated study drug in Cohort 2. Doravirine geometric mean (GM) AUC0-∞ was 34.8 μM∙h and GM C24 was 514 nM following a single dose, with a predicted steady state GM C24,ss,pred of 690 nM. Cohort 2 enrolled adolescents weighing ≥ 45 kg. Plasma concentrations of doravirine, tenofovir and lamivudine achieved by Cohort 2 participants were similar to those reported in adults. No drug-related serious or grade 3 or 4 adverse events occurred. Forty-two of 45 participants (93.3%; 95% CI [81.7, 98.6]) achieved or maintained HIV-1 RNA <40 copies/mL.

CONCLUSIONS: Doravirine and DOR FDC achieved target PK in adolescents with HIV-1. DOR FDC was well tolerated and maintained excellent virologic efficacy through 24 weeks, offering a favorable option for adolescents.

PMID:36215957 | DOI:10.1097/QAI.0000000000003116

Epilepsy Behav. 2022 Oct 7;136:108937. doi: 10.1016/j.yebeh.2022.108937. Online ahead of print.

ABSTRACT

OBJECTIVE: Perampanel (PER) has previously been shown to be effective and tolerable when used as an adjunctive therapy for patients with focal-onset seizures (FOS). This study aimed to evaluate the effect of PER as adjunctive therapy for patients with FOS in the Chinese population under real-world conditions for 1 year.

METHODS: A prospective, single-center, 1-year observational study was conducted at Huashan Hospital, enrolling both under age (≥4 years old) and adult patients with FOS. Response to PER was assessed at 3-, 6-, and 12-month checkpoints by analyzing the 50 % responder rate, the seizure-free rate, and reduction in seizure frequency.

RESULTS: One hundred and eight patients (mean age: 26.6 years, 56.5 % males) with FOS were included, with seventy-six patients finishing the 1-year follow-up (retention rate: 70.4 %, mean PER dose: 4.3 mg/day). The seizure frequency was reduced significantly at 3, 6, and 12 months relative to baseline (p < 0.001 for each seizure type). At 12 months, the responder rate was 65.8 %, and the seizure-free rate was 39.5 %. A significantly higher responder rate was found in patients with focal to bilateral tonic-clonic seizures (p = 0.024), among which the percentage of patients with sleep-related epilepsy was significantly high (p = 0.045). Responders had a lower number of concomitant anti-seizure medications (ASMs) than the non-responders (p = 0.009). Drug-related adverse events (AEs) were reported in 37 % of patients, mostly mild or moderate, and the patients who experienced AEs had a higher daily dose of PER than those who did not (p = 0.026).

CONCLUSION: Perampanel, an add-on therapy for focal-onset seizures, was found to be effective and tolerable in Chinese patients at 12 months.

PMID:36215830 | DOI:10.1016/j.yebeh.2022.108937

Ther Adv Drug Saf. 2022 Oct 5;13:20420986221127501. doi: 10.1177/20420986221127501. eCollection 2022.

ABSTRACT

Self-medication (SM) is a global and growing phenomenon. It represents a public health problem due to antibiotic resistance, risk of adverse drug reactions, drug-drug interactions, disease masking, and increased morbidity. There is not a consensus on the definition of SM. The definitions found in different studies make it difficult to address this problem from a theoretical perspective and therefore find an adequate solution to this public health problem. The aim of this article is to search the medical literature to characterize the current understanding of SM in the medical community. We conducted a scoping review of definitions of SM by searching on PubMed - Medline, Embase, and LILACS using the following combination of keywords: 'self-prescription' or 'self prescription', 'self-medication' or 'self medication', or 'automedication' and 'definition' or 'explanation'. The search was limited to articles containing the definition of SM, with no limit on language or year. Duplicate studies and those that did not mention the definition of SM were excluded from the final review. A total of 65 studies were included in the final selection. We found a vast heterogeneity in the definition of SM. Most articles based their definition of SM on the process of obtaining the drug, the nonparticipation of a specific health professional, the source of the medication, and the reason for SM. Other interesting concepts such as self-care, nonadherence to a prescription, reuse of stored drugs, and sharing and lending medicines were also considered forms of SM by other authors, however. This study highlights the need to reach a consensus regarding the definition of SM to adequately propose strategies to address this global health problem. This study shows the diverse concepts that need to be included in a future definition of SM.

PLAIN LANGUAGE SUMMARY: Definition of self-medication: a review with systematic methodology Self-medication (SM) is a global and growing phenomenon that represents a public health problem due to antibiotic resistance, risk of dangerous side effects, interactions between drugs, and disease masking. Currently, there is not a consensus on the definition of SM, which makes it difficult to address this problem and therefore find an adequate solution. Making a standard definition would allow the development of programs focused on addressing drug-related problems associated with self-medication behavior. The purpose of this article is to search the medical literature to define the current understanding of SM in the medical community. We included a total of 65 studies and found a great variance in the definition of SM. Most articles based their definition of SM on the process of obtaining the drug, the nonparticipation of a specific health professional, the source of the medication, and the reason for SM. Other interesting concepts such as self-care, not following a prescription, reuse of stored drugs, and sharing and lending medicines were also considered forms of SM by other authors, however. Furthermore, this study highlights that SM is a wider concept that goes beyond aiming to promote and restore health, as aesthetic and recreational purposes are also reasons for SM that can put individuals at risk and compromise the correct and safe use of medications.

PMID:36211626 | PMC:PMC9537481 | DOI:10.1177/20420986221127501

Clin Geriatr Med. 2022 Nov;38(4):727-732. doi: 10.1016/j.cger.2022.05.012. Epub 2022 Sep 14.

ABSTRACT

Polypharmacy in the emergency department (ED) presents additional challenges for older adults with acute illnesses but is also an opportunity for healthcare providers to prevent adverse drug events as well as the use of potentially inappropriate medications. Older patients have complex health-related needs and are at risk for medication-related complications during an ED visit. Implementing mitigating strategies of performing medication reconciliation and review, using existing implicit or explicit tools to evaluate medications, and deprescribing or de-escalating high-risk medications are critical to positive health outcomes. These practices can help to optimize pharmacologic interventions for older patients in the ED.

PMID:36210088 | DOI:10.1016/j.cger.2022.05.012

Clin Geriatr Med. 2022 Nov;38(4):705-714. doi: 10.1016/j.cger.2022.05.010. Epub 2022 Sep 13.

ABSTRACT

Polypharmacy, defined as taking five medications or more, is a common geriatric syndrome. It is especially prevalent in older adults with cancer. For older patients with breast, lung, prostate, and colorectal cancer and chronic lymphocytic leukemia, polypharmacy has numerous adverse effects, including interactions with medications prescribed for other comorbidities. Polypharmacy is influenced by drug-drug interactions and can reduce the efficacy of systemic cancer therapeutics. It is also associated with worse progression-free and overall survival for some cancers such as lung and colorectal cancer. This highlights the need for a judicious review of all medications and the role of interventions in improving quality of life and survival.

PMID:36210086 | DOI:10.1016/j.cger.2022.05.010

Clin Geriatr Med. 2022 Nov;38(4):667-684. doi: 10.1016/j.cger.2022.07.011.

ABSTRACT

Care for the hospitalized older adult is made more complex by polypharmacy that can increase the risks of adverse drug events. This article reviews polypharmacy in the hospitalized older adult from their admission to hospitalization and transition of care as well as highlighting principles to reduce polypharmacy and tools for deprescribing during hospitalization. We review common reasons for admission and how these conditions may be particularly affected by or contribute to polypharmacy in older adults.

PMID:36210083 | DOI:10.1016/j.cger.2022.07.011

Orv Hetil. 2022 Oct 9;163(41):1614-1628. doi: 10.1556/650.2022.32635. Print 2022 Oct 9.

ABSTRACT

The epidemiological indicators of malignant diseases and diabetes are changing similarly, as lately both have been dynamically increasing worldwide. They occur usually in the same patient synchronously or metachronously, because of their common metabolic and molecular background. Consequently, in more and more cases they require common treatment. That has led to a new science, called oncodiabetology, the main purpose of which is to optimize the combination of antineoplastic and antidiabetic therapies. Regarding the antineoplastic agents, their complex influence on metabolism has to be considered, especially diabetogenic side effects inducing insulin-resistance and decreasing insulin production. According to antidiabetic agents' role in preventing tumors, diminishing toxicity of cytostatic drugs, and promoting the breakthrough of chemoresistance should be considered. In this study, we investigate the contexts of antineoplastic agents' efficiency and the glucometabolism of the organization, the characteristics of oncotherapy in patients suffering from malignant disease and diabetes, and review those cytostatic agents, having massive diabetogenic adverse effects. We describe the properties and subtypes of secondary diabetes, thoroughly discuss the specific characteristics of hyperglycaemia and diabetes caused by malignant diseases and antineoplastic treatments, especially pancreatic diabetes. In the end, we attempt to determine the proper place and role of oncodiabetology in the treatment of patients suffering from malignancies. During our investigation, we assessed the effects on glucometabolism of the recently used classic cytostatics, molecularly targeted therapies and different endocrine manipulations treating malignancies. We reviewed the schedules and scientific background of almost 300 medicines for this aim. We established that every third antineoplastic agent influenced glucometabolism adversely. We report our further observations in our next reviews. Orv Hetil. 2022; 163(41): 1614-1628.

PMID:36209421 | DOI:10.1556/650.2022.32635

Breast. 2022 Sep 30;66:85-88. doi: 10.1016/j.breast.2022.09.009. Online ahead of print.

ABSTRACT

BACKGROUND: Since breast cancer is less common in men than in women, data on the use of new therapeutic agents, including cyclin-dependent kinase 4-6 (CDK 4-6) inhibitors, are limited in patients with metastatic hormone receptor positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) male breast cancer. Therefore; we aimed to investigate the treatment responses of metastatic HR+, HER2-male breast cancer patients treated with CDK 4-6 inhibitors in a multicenter real-life cohort.

METHODS: Male patients with a diagnosis of HR+ and HER2-metastatic breast cancer, treated with any CDK 4-6 inhibitor, were included in the study. Demographic and clinical characteristics of the patients were recorded. We aimed to determine progression-free survival (PFS) time, response rates and drug related side effects.

RESULTS: A total 25 patients from 14 institutions were recruited. The mean age at diagnosis was 57 years. Median follow-up was 19.53 (95% CI: 14.04-25.02) months. The overall response rate was 60%. While the median PFS was 20.6 months in the whole cohort, it wasn't reached in those using CDK 4-6 inhibitors in first line and 10 months in the subsequent lines (p:0.009). No new adverse events were encountered.

CONCLUSION: In our study, we found that CDK 4-6 inhibitors are effective and safe options in men with HR+ and HER2-metastatic breast cancer as in women. Our results support the use of CDK 4-6 inhibitor-based combinations in the first-line treatment of HR+ and HER2-metastatic male breast cancer.

PMID:36208540 | DOI:10.1016/j.breast.2022.09.009

Eur J Hosp Pharm. 2022 Oct 7:ejhpharm-2022-003485. doi: 10.1136/ejhpharm-2022-003485. Online ahead of print.

ABSTRACT

Autoimmune hepatitis (AIH) is a non-contagious, chronic, inflammatory autoimmune disease in which one's own immune system attacks healthy, normal hepatic cells. The exact cause of AIH is unknown; however, the combination of genetic, environmental (eg, drugs and natural infection) and immunological factors may lead to AIH. AIH may also be potentiated with the use of vaccines: this case reports one such event following immunisation, along with 1 year of follow-up. A female patient in her late 20s presented to the hospital with yellowish discolouration of eyes, urine and stools. Her medical history revealed that she had been vaccinated with the first dose of a COVID-19 vaccine 10 days earlier. She had a history of asymptomatic COVID-19 infection 3 months ago and a history of chronic analgesic consumption for migraine. She was diagnosed as having AIH through extensive clinical and laboratory workup. This case may be an immediate enhancement of a hidden autoimmune disorder triggered by the vaccination. This adverse event following immunisation has an adequate temporal relationship with her COVID-19 vaccine. The causality can be categorised as 'indeterminate' and may be considered as a potential signal following COVID-19 vaccination.

PMID:36207131 | DOI:10.1136/ejhpharm-2022-003485

Actas Dermosifiliogr. 2022 Oct 4:S0001-7310(22)00810-9. doi: 10.1016/j.ad.2021.10.021. Online ahead of print.

NO ABSTRACT

PMID:36206808 | DOI:10.1016/j.ad.2021.10.021

Kidney Med. 2022 Aug 27;4(10):100538. doi: 10.1016/j.xkme.2022.100538. eCollection 2022 Oct.

ABSTRACT

RATIONALE & OBJECTIVE: Venglustat, a glucosylceramide synthase inhibitor, inhibits cyst growth and reduces kidney failure in mouse models of autosomal dominant polycystic kidney disease (ADPKD). STAGED-PKD aims to determine the safety and efficacy of venglustat and was designed using patient enrichment for progression to end-stage kidney disease and modeling from prior ADPKD trials.

STUDY DESIGN: STAGED-PKD is a 2-stage, international, double-blind, randomized, placebo-controlled trial in adults with ADPKD (Mayo Class 1C-1E) and estimated glomerular filtration rate (eGFR) 45-<90 mL/min/1.73 m2 at risk of rapidly progressive disease. Enrichment for rapidly progressing patients was identified based on retrospective analysis of total kidney volume (TKV) and eGFR slope from the combined Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease and HALT Progression of Polycystic Kidney Disease A studies.

SETTING & PARTICIPANTS: Target enrollment in stages 1 and 2 was 240 and 320 patients, respectively.

INTERVENTIONS: Stage 1 randomizes patients 1:1:1 to venglustat 8 mg or 15 mg once daily or placebo. Stage 2 randomizes patients 1:1 to placebo or venglustat, with the preferred dose based on stage 1 safety data.

OUTCOMES: Primary endpoints are TKV growth rate over 18 months in stage 1 and eGFR slope over 24 months in stage 2. Secondary endpoints include: annualized rate of change in eGFR from baseline to 18 months (stage 1); annualized rate of change in TKV based on magnetic resonance imaging from baseline to 18 months (stage 2); and safety, tolerability, pain, and fatigue (stages 1 and 2).

LIMITATIONS: If stage 1 is unsuccessful, patients enrolled in the trial may develop drug-related adverse events that can have long-lasting effects.

CONCLUSIONS: Modeling allows the design and powering of a 2-stage combined study to assess venglustat's impact on TKV growth and eGFR slope. Stage 1 TKV assessment via a nested approach allows early evaluation of efficacy and increased efficiency of the trial design by reducing patient numbers and trial duration.

FUNDING: This study was funded by Sanofi.

TRIAL REGISTRATION: STAGED-PKD has been registered at ClinicalTrials.gov with study number NCT03523728.

PMID:36204243 | PMC:PMC9529969 | DOI:10.1016/j.xkme.2022.100538

Front Pharmacol. 2022 Sep 20;13:948339. doi: 10.3389/fphar.2022.948339. eCollection 2022.

ABSTRACT

Antibacterial drugs are a widely used drug class due to the frequency of infectious diseases globally. Risks knowledge should ground these medicines' selection. Data mining in large databases is essential to identify early safety signals and to support pharmacovigilance systems. We conducted a cross-sectional study to assess adverse drug events related to antibiotics reporting between December 2018 and December 2021 in the Brazilian database (Vigimed/VigiFlow). We used the Reporting Odds Ratio (ROR) disproportionality analysis method to identify disproportionate reporting signals (SDR), referring to statistical combinations between drugs and adverse events. Vancomycin was the most reported antibiotic (n = 1,733), followed by ceftriaxone (n = 1,277) and piperacillin and tazobactam (n = 1,024). We detected 294 safety signals related to antibacterials. We identified azithromycin leading in the number of safety signals (n = 49), followed by polymyxin B (n = 25). Of these, 95 were not provided for in the drug label and had little or no reports in the medical literature. Three serious events are associated with ceftazidime and avibactam, a new drug in the Brazilian market. We also found suicide attempts as a sign associated with amoxicillin/clavulanate. Gait disturbance, a worrying event, especially in the elderly, was associated with azithromycin. Our findings may help guide further pharmacoepidemiologic studies and monitoring safety signals in pharmacovigilance.

PMID:36204235 | PMC:PMC9530932 | DOI:10.3389/fphar.2022.948339

Chem Res Toxicol. 2022 Oct 17;35(10):1777-1788. doi: 10.1021/acs.chemrestox.2c00188. Epub 2022 Oct 6.

ABSTRACT

Glucuronidation and CoA (coenzyme A) conjugation are common pathways for the elimination of carboxylic acid-containing drug molecules. In some instances, these biotransformations have been associated with toxicity (such as idiosyncratic hepatic injury, renal impairment, hemolytic anemia, gastrointestinal inflammation, and bladder cancer) attributed to, in part, the propensity of acyl glucuronides and acyl CoA thioesters to covalently modify biological macromolecules such as proteins and DNA. It is to be noted that, while acyl glucuronidation and CoA conjugation are indeed implicated in adverse effects, there are many safe drugs in the market that are cleared by these reactive pathways. It is therefore important that new molecular entities with carboxylic acid groups are evaluated for toxicity in a manner that is not unreasonably risk-averse. In the absence of truly predictable methods, therefore, the general approach is to apply a set of end points to generate a weight-of-evidence evaluation. In practice, the focus is to identify structural liabilities and provide structure-activity recommendations early in the program, at a stage where an attempt to improve reactive metabolism does not deoptimize other critical drug-quality criteria. This review will present a high-level overview of the chemistry of glucuronidation and CoA conjugation and provide a discussion of the possible mechanisms of adverse effects that have been associated with these pathways, as well as how such potential hazards are addressed while delivering a new chemical entity for clinical evaluation.

PMID:36200746 | DOI:10.1021/acs.chemrestox.2c00188

J Med Internet Res. 2022 Oct 6;24(10):e35464. doi: 10.2196/35464.

ABSTRACT

BACKGROUND: Pharmacovigilance using real-world data (RWD), such as multicenter electronic health records (EHRs), yields massively parallel adverse drug reaction (ADR) signals. However, proper validation of computationally detected ADR signals is not possible due to the lack of a reference standard for positive and negative associations.

OBJECTIVE: This study aimed to develop a reference standard for ADR (RS-ADR) to streamline the systematic detection, assessment, and understanding of almost all drug-ADR associations suggested by RWD analyses.

METHODS: We integrated well-known reference sets for drug-ADR pairs, including Side Effect Resource, Observational Medical Outcomes Partnership, and EU-ADR. We created a pharmacovigilance dictionary using controlled vocabularies and systematically annotated EHR data. Drug-ADR associations computed from MetaLAB and MetaNurse analyses of multicenter EHRs and extracted from the Food and Drug Administration Adverse Event Reporting System were integrated as "empirically determined" positive and negative reference sets by means of cross-validation between institutions.

RESULTS: The RS-ADR consisted of 1344 drugs, 4485 ADRs, and 6,027,840 drug-ADR pairs with positive and negative consensus votes as pharmacovigilance reference sets. After the curation of the initial version of RS-ADR, novel ADR signals such as "famotidine-hepatic function abnormal" were detected and reasonably validated by RS-ADR. Although the validation of the entire reference standard is challenging, especially with this initial version, the reference standard will improve as more RWD participate in the consensus voting with advanced pharmacovigilance dictionaries and analytic algorithms. One can check if a drug-ADR pair has been reported by our web-based search interface for RS-ADRs.

CONCLUSIONS: RS-ADRs enriched with the pharmacovigilance dictionary, ADR knowledge, and real-world evidence from EHRs may streamline the systematic detection, evaluation, and causality assessment of computationally detected ADR signals.

PMID:36201386 | DOI:10.2196/35464

Pharmazie. 2022 Sep 1;77(7):243-247. doi: 10.1691/ph.2022.2416.

ABSTRACT

Proton pump inhibitors (PPIs) are commonly used for the prevention or treatment of gastric ulcers, but they can induce hypomagnesemia. Little is known about the onset duration and risk factors related to patient characteristics of this adverse event in Japanese patients. Therefore, we analyzed the time-to-onset of PPI-induced hypomagnesemia and evaluated the association between hypomagnesemia and PPIs using the Japanese Adverse Drug Event Report (JADER) database. We analyzed hypomagnesemia cases between 2004 and 2021. The time-to-onset analysis was performed using the Weibull distribution, and the adjusted reporting odds ratio (aROR) or 95% confidence interval (95% CI) was calculated using a multiple logistic regression analysis. The analysis database comprised 236,525 cases, with 188 cases associated with hypomagnesemia. The median onset duration (interquartile range) of PPI-induced hypomagnesemia was 99.0 (51.8-285.5 ) days, which is considered the random failure type. The multiple logistic regression analysis revealed that hypomagnesemia is significantly associated with male sex (aROR, 95% CI: 1.66, 1.23-2.25) , age < 60 (1.59, 1.14-2.21) , estimated body-mass index (eBMI) (0.94, 0.91-0.98) , PPIs (1.66, 1.18-2.30) , and the interaction of age (<60)*PPIs (1.58, 1.13-2.19) . However, diuretics were not significantly associated with hypomagnesemia. Our results suggest that serum magnesium levels should be measured regularly regardless of the duration of PPI use, especially in patients with male sex, age < 60, or low BMI. These findings will assist health professionals in the adequate use of PPIs. These findings need to be evaluated by cohort studies and long-term clinical investigations.

PMID:36199184 | DOI:10.1691/ph.2022.2416

Pharmazie. 2022 Sep 1;77(7):255-261. doi: 10.1691/ph.2022.2386.

ABSTRACT

The aim of the present study was to survey adverse drug events (ADEs) in patients with bipolar disorders and identify risk factors using the Japanese Adverse Drug Event Report (JADER) database, a spontaneous reporting system. Data on patients with bipolar disorders were extracted from the JADER database. The Medical Dictionary for Regulatory Activities (MedDRA) preferred terms (PT) and standardized MedDRA queries (SMQ) were used to define ADEs. A multiple logistic regression analysis was performed to identify risk factors for ADEs. A total of 8653 reports of 1108 types of ADEs (PT) were registered in data collected on 3521 patients with bipolar disorders. Rash (PT) was the most frequently reported in 549 patients, followed by drug eruption (PT) in 387, fever (PT) in 364, toxicity to various agents (PT) in 291, and Stevens-Johnson syndrome (PT) in 261. Among 24 ADEs (PT) that were reported in more than 50 patients, lamotrigine was associated with increased risks of 13 ADEs (PT), followed by carbamazepine with increased risks of 8 ADEs (PT). The majority of these ADEs belonged to hypersensitivity (SMQ) or hepatic disorder (SMQ). Lithium carbonate was associated with increased risks of rash (PT), drug interaction (PT), and tubulointerstitial diseases (SMQ). All antipsychotics increased the adjusted odds ratio for neuroleptic malignant syndrome (PT). The risk of hyperglycemia/new onset diabetes mellitus (SMQ) was increased by olanzapine, quetiapine fumarate, and risperidone. We are presenting the profiles of ADEs in patients with bipolar disorders using the JADER database, and propose risk factors for 19 ADEs (PT) and 4 ADEs (SMQ).

PMID:36199180 | DOI:10.1691/ph.2022.2386

Front Pharmacol. 2022 Sep 19;13:1022266. doi: 10.3389/fphar.2022.1022266. eCollection 2022.

ABSTRACT

As a traditional Chinese herbal medicine, Panax ginseng C. A. Meyer (PG) has preventive and therapeutic effects on various diseases. Ginsenosides are main active ingredients of PG and have good pharmacological effects. Due to the diversity of chemical structures and physicochemical properties of ginsenosides, Currently, related studies on PG monomer saponins are mainly focused on the cardiovascular system, nervous system, antidiabetic, and antitumor. There are few types of research on the toxin treatment, predominantly exogenous toxicity. PG and its monomer ginsenosides are undoubtedly a practical option for treating exogenous toxicity for drug-induced or metal-induced side effects such as nephrotoxicity, hepatotoxicity, cardiotoxicity, metal toxicity and other exogenous toxicity caused by drugs or metals. The mechanism focuses on antioxidant, anti-inflammatory, and anti-apoptotic, as well as modulation of signaling pathways. It summarized the therapeutic effects of ginseng monomer saponins on exogenous toxicity and demonstrated that ginsenosides could be used as potential drugs to treat exogenous toxicity and reduce drug toxicities.

PMID:36199681 | PMC:PMC9527293 | DOI:10.3389/fphar.2022.1022266

Cureus. 2022 Sep 1;14(9):e28683. doi: 10.7759/cureus.28683. eCollection 2022 Sep.

ABSTRACT

Background and aims Peripheral neuropathy is a frequent complication of long-standing diabetes mellitus that adversely affects the quality of life. Pregabalin (anticonvulsant) and duloxetine (antidepressant) are often prescribed for diabetic peripheral neuropathic pain. This study aimed to determine and compare the efficacy and safety of pregabalin and duloxetine in patients with diabetic peripheral neuropathic pain. Materials and methods This prospective observational study was conducted at District Headquarter (DHQ) Hospital, Daggar, Buner district, Pakistan, from February 15 to July 15, 2022, after approval from the Institutional Research and Ethical Review Board. Confirmation of diabetic peripheral neuropathy was based on the history of diabetes mellitus and vibration perception threshold (VPT) using a biothesiometer. The cut-off was set at 15 volts. VPT of more than 15 volts was considered confirmatory for peripheral neuropathy. Patients were divided equally into two groups. Baseline visual analog scale (VAS) score was recorded for all patients. Tablet pregabalin 300 mg daily was administered for four weeks to one group, while tablet duloxetine in 60 mg strength daily was administered to the other group. VAS score after four-week treatment was recorded and compared. Adverse events experienced by the patient were also noted. Results A total of 86 patients were enrolled. The patient ages ranged from 30 to 80 years. Baseline characteristics, including mean age, mean BMI, and mean disease duration of duloxetine versus pregabalin group, were 50.30 ± 8.55 versus 48.20 ± 8.99 years, 23.47 ± 1.23 versus 23.10 ± 1.59 kg/m2 and 21.64 ±7.41 versus 20.04±6.37 months respectively. Duloxetine effectively controlled peripheral neuropathic pain in 81.4% of patients compared to pregabalin in 74.4% of patients. Severe drug-related adverse reactions were observed in 4.6% of patients with duloxetine compared to 0% with pregabalin. Conclusion Duloxetine and pregabalin effectively reduce diabetes-related peripheral neuropathic pain. However, duloxetine has slightly better outcomes than pregabalin. The safety profile of pregabalin is better than duloxetine.

PMID:36199645 | PMC:PMC9526783 | DOI:10.7759/cureus.28683