Antibiotics (Basel). 2022 Oct 13;11(10):1410. doi: 10.3390/antibiotics11101410.

ABSTRACT

Patients in intensive care units (ICU) are at high risk to experience potential drug-drug interactions (pDDIs) because of the complexity of their drug regimens. Such pDDIs may be driven by pharmacokinetic or pharmacodynamic mechanisms with clinically relevant consequences in terms of treatment failure or development of drug-related adverse events. The aim of this paper is to review the pharmacokinetic-driven pDDIs involving antibiotics in ICU adult patients. A MEDLINE Pubmed search for articles published from January 2000 to June 2022 was completed matching the terms "drug-drug interactions" with "pharmacokinetics", "antibiotics", and "ICU" or "critically-ill patients". Moreover, additional studies were identified from the reference list of retrieved articles. Some important pharmacokinetic pDDIs involving antibiotics as victims or perpetrators have been identified, although not specifically in the ICU settings. Remarkably, most of them relate to the older antibiotics whereas novel molecules seem to be associated with a low potential for pDDIs with the exceptions of oritavancin as potential perpetrator, and eravacicline that may be a victim of strong CYP3A inducers. Personalized therapeutic drug regimens by means of available web-based pDDI checkers, eventually combined with therapeutic drug monitoring, when available, have the potential to improve the response of ICU patients to antibiotic therapies.

PMID:36290068 | DOI:10.3390/antibiotics11101410

Med J Aust. 2022 Nov 21;217(10):502-504. doi: 10.5694/mja2.51755. Epub 2022 Oct 26.

NO ABSTRACT

PMID:36287028 | DOI:10.5694/mja2.51755

Ter Arkh. 2021 Nov 15;93(11):1368-1374. doi: 10.26442/00403660.2021.11.201195.

ABSTRACT

The article describes a clinical observation of a severe course of a sporadic case of foodborne botulism in a woman at 32 weeks gestation with a successful resolution of pregnancy by independent childbirth. No adverse effects of botulism on pregnancy, delivery, and fetal development were noted. Anti-botulinum serum was administered to the patient no earlier than 96 hours from the onset of the disease. The paper analyzes the clinical picture of botulism, on the basis of which it is necessary to carry out a differential diagnosis.

PMID:36286661 | DOI:10.26442/00403660.2021.11.201195

Eur J Hosp Pharm. 2022 Nov;29(6):329-335. doi: 10.1136/ejhpharm-2020-002554. Epub 2021 Apr 1.

ABSTRACT

OBJECTIVE: Off-label drug use seems to be integral to adult palliative care pharmacotherapy. Balancing potential risks and benefits in the context of limited therapeutic options is challenging. To provide specific support for clinicians in dealing with off-label use, it is essential to understand off-label use in everyday clinical practice. The aim of this pilot study was to quantify and describe off-label use in an adult palliative care unit.

METHODS: Retrospective chart review of all adult patients treated on a palliative care unit in October 2017. All data on drug use (eg, indication, dose, route of administration) were extracted and matched with the prescribing information. Identified off-label use was subsequently compared with recommendations in the relevant literature. The main outcome measure was frequency and type of off-label drug use.

RESULTS: Some 2352 drug application days and 93 drugs were identified for 28 patients. Of all drugs, 47 (51%) were used off-label at least once. Most off-label uses concerned indication (57%) followed by mode of administration. In drugs highly relevant to palliative care the rate of off-label use was as high as 67%. The extent to which off-label therapy was supported by literature was very variable and ranged from 0% to 88%.

CONCLUSIONS: These data from a single unit confirm the high prevalence of off-label use in palliative medicine and demonstrate that off-label use in adult palliative care is multifaceted. The data presented allow for a more precise characterisation of various aspects of off-label use in order to derive concrete further measures for research and clinical practice.

PMID:36283723 | DOI:10.1136/ejhpharm-2020-002554

Cureus. 2022 Sep 14;14(9):e29145. doi: 10.7759/cureus.29145. eCollection 2022 Sep.

ABSTRACT

Purpose This study aims to describe the magnetic resonance imaging (MRI) of the brain of five patients diagnosed with metronidazole-induced encephalopathy (MIE). In addition, the aim of our study was to better define the topographic distribution of lesions in MIE. Methods We retrospectively evaluated MRI findings before and after drug cessation in five patients diagnosed with MIE at Era's Lucknow Medical College and Hospital, Lucknow, Uttar Pradesh, India. The main MRI signal changes and lesion locations were studied. Results Among the patients observed, the average age of the patients with MIE was 55 years (range: 30-70 years). Cerebellar dysfunction, mainly ataxia, and altered mental status were seen in the majority of cases. The most frequently involved sites were the dentate nucleus (cerebellum), brain stem, and corpus callosum (splenium). In diffusion-weighted imaging (DWI), most lesions did not show true restricted diffusion, except for a solitary corpus callosum lesion. Conclusion Although drug-related side effects are more common with long-term use of metronidazole, they may also occur with high doses for short durations. The dentate nucleus, the splenium in the corpus callosum, and the brain stem are the most affected structures. Apart from a solitary lesion of the corpus callosum, all identified lesions were reversible at follow-up MRI after discontinuation of metronidazole. The clinical presentation and characteristic MRI changes are highly specific and can be correlated to make a rapid and more accurate diagnosis of this potentially treatable condition. Prognosis is excellent if detected early.

PMID:36282977 | PMC:PMC9573127 | DOI:10.7759/cureus.29145

Drugs. 2022 Oct 25. doi: 10.1007/s40265-022-01794-0. Online ahead of print.

ABSTRACT

Ripretinib (Qinlock®) is a small molecule inhibitor of the receptor tyrosine kinases KIT and platelet-derived growth factor receptor α (PDGFRA) and is approved for the treatment of gastrointestinal stromal tumours as a fourth-line of therapy. After successive cycles of treatment, gastrointestinal stromal tumours can carry a wide array of mutations, which makes resistance to treatment more likely. Ripretinib has a dual mechanism of action that allows it to target a broad spectrum of mutations in KIT or PDGFRA. The pivotal phase III INVICTUS trial demonstrated an increase of progression-free survival in patients receiving ripretinib compared with placebo, with efficacy being maintained across patients with KIT exon 9, 11, 13 and 17 mutations. Ripretinib has acceptable tolerability, with the most common drug-related grade 3 or 4 adverse events being lipase increases, hypertension, fatigue and hypophosphataemia. Ripretinib is therefore a valuable additional line of therapy available for the management of gastrointestinal stromal tumours.

PMID:36282417 | DOI:10.1007/s40265-022-01794-0

Discov Med. 2022 May-Jun;33(170):137-141.

ABSTRACT

Immune checkpoint inhibitors (ICIs) are novel immunotherapy drugs that have significantly improved the outcomes of a variety of cancers including lung cancer. However, ICIs could induce immune-related adverse effects (irAEs) characterized by clinical manifestations that resemble autoimmune disorders. The main type of IrAEs in the kidneys is acute kidney injury (AKI). In this review, we describe the types of ICIs targeting lung cancer, especially those approved by the U.S. Food and Drug Administration for clinical trials in lung cancer patients. Next, we summarize current understandings of the mechanisms involved in ICIs-induced AKI. Finally, we highlight further directions to address ICIs-associated AKI for the benefits of lung cancer patients in the clinic.

PMID:36274242

Front Pharmacol. 2022 Oct 7;13:1039558. doi: 10.3389/fphar.2022.1039558. eCollection 2022.

ABSTRACT

Drug-induced liver injury (DILI) is a serious clinical disease associated with reactive oxygen species (ROS) burst and subsequent inflammatory responses. However, traditional treatments were limited by low efficacy and serious side effects due to the special liver structure. Here, we developed a molybdenum (Mo)-based nanoparticles, EGM NPs, after overall consideration of the pathophysiology of DILI and the advantages of nanodrugs. It demonstrated that EGM NPs treated acetaminophen (APAP)-induced DILI by scavenging ROS and inhibiting inflammation. EGM NPs effectively scavenged various ROS and reduced cell apoptosis at the cellular level. More importantly, EGM NPs can treat APAP-induced DILI in vivo, reducing the levels of liver function indicators in mice with liver injury, scaling down the area of hepatocyte necrosis and successfully inhibiting endoplasmic reticulum (ER) stress in the liver. EGM NPs also showed a certain anti-inflammatory effect by reducing infiltration of macrophages, decreasing pro-inflammatory factors and inhibiting the expression levels of inducible nitric oxide synthase (NOS2) and myeloperoxidase (MPO). Collectively, our findings suggest that EGM NPs-based nanotherapeutic is a novel strategy for the treatment of DILI.

PMID:36278211 | PMC:PMC9585210 | DOI:10.3389/fphar.2022.1039558

Front Pharmacol. 2022 Oct 5;13:961863. doi: 10.3389/fphar.2022.961863. eCollection 2022.

ABSTRACT

Probability of target attainment is the key factor influencing the outcome of meropenem therapy. The objective of the present study was to evaluate the relationship between the time in which the plasma free concentration of meropenem exceeds the minimum inhibitory concentration of pathogens (fT >MIC) during therapy and the clinical outcome of treatment to optimize meropenem therapy. Critically ill children with infections who had received intravenous meropenem monotherapy were included. The relationship between fT >MIC of meropenem and effectiveness and safety were explored. Data from 53 children (mean age ± standard deviation, 26 months ± 38) were available for final analysis. Children with fT >MIC ≥ 5.6 h (n = 14) had a more significant improvement in antibacterial efficacy in terms of decrease in fever (p = 0.02), white blood cell count (p = 0.014), and C-reactive protein (p = 0.02) compared with children with fT >MIC < 5.6 h (n = 39) after meropenem therapy completed. No drug-related adverse events were shown to have a causal association with meropenem therapy. Our study shows the clinical benefits of sufficient target attainment of meropenem therapy. Meeting a suitable pharmacodynamic target attainment of meropenem is required to ensure better antibacterial efficacy in critically ill infants and children. Clinical Trial Registration: clinicaltrials.gov, Identifier NCT03643497.

PMID:36278190 | PMC:PMC9581397 | DOI:10.3389/fphar.2022.961863

Pharmazie. 2022 Oct 1;77(10):307-310. doi: 10.1691/ph.2022.2453.

ABSTRACT

Long-term voriconazole use may increase the risk of cutaneous squamous cell carcinoma (cSCC), especially in immunocompromised patients. However, relatively little is known regarding voriconazole-induced cSCC in Japan. Thus, the purpose of this study was to evaluate the association between voriconazole use and cSCC in Japan using different national pharmacovigilance databases. First, using the Japanese Adverse Drug Event Report (JADER) database, we evaluated the association between voriconazole use and cSCC in Japan. Second, using the U. S. Food and Drug Administration Adverse Event Reporting System (FAERS) database, we examined regional differences in the occurrence of voriconazole-induced cSCC between Japan and other countries. We calculated reporting odds ratios (RORs) as disproportionality analysis to evaluate voriconazole-induced cSCC. In this study, cases in which one or more of "Bowen's disease", "Carcinoma in situ of skin", "Keratoacanthoma", "Squamous cell carcinoma in skin", or "Squamous cell carcinoma" were reported as adverse events were considered to be cSCC cases. The analysis based on the JADER database showed an association between voriconazole use and cSCC in Japan, with a ROR (95% confidence interval) of 35.37 (25.60-48.87). Further, the analysis based on the FAERS database revealed that signals were detected in Japan as well as in Western countries and Australia. This study is the first in which the association between voriconazole use and cSCC in Japan is assessed using national pharmacovigilance databases. Healthcare providers need to be fully aware of the potential for cSCC development owing to voriconazole use and in all countries, including Japan, ensure careful follow-up of patients' skin.

PMID:36273254 | DOI:10.1691/ph.2022.2453

Chest. 2022 Oct 20:S0012-3692(22)04004-1. doi: 10.1016/j.chest.2022.10.013. Online ahead of print.

ABSTRACT

BACKGROUND: The most commonly used topical haemostatic agents during flexible bronchoscopy (FB) are cold saline and adrenaline. Data on usage of other agents such as tranexamic acid (TXA) for this purpose are limited.

RESEARCH QUESTION: Is TXA effective and safe in controlling iatrogenic bleeding during FB compared to adrenaline?

STUDY DESIGN AND METHODS: We conducted a cluster-randomized, double blind, single centre trial in a tertiary teaching hospital. Patients were randomized in weekly clusters to receive up to 3 applications of TXA (100mg, 2ml) or adrenaline (0.2mg, 2ml, 1:10000) following haemostasis failure after 3 applications of cold saline (4°C, 5ml). Crossover was allowed (for up to 3 further applications) before proceeding with other interventions. Bleeding severity was graded by the bronchoscopist using a visual analogue scale (VAS; 1 - very mild, 10 - severe).

RESULTS: A total of 2033 FB were performed and 130 patients were successfully randomized to adrenaline (N=65) or TXA (N=65), while 12 had to be excluded for protocol violations (2 from the adrenaline and 10 from TXA arm). Bleeding was stopped in 83.1% (54/65) of patients in both groups (p=1). The severity of bleeding and number of applications needed for bleeding control (N) were similar in both groups (adrenaline mean VAS= 4.9±1.3, N=1.8±0.8; TXA mean VAS=5.3±1.4, N=1.8±0.8). Both adrenaline and TXA were more successful in controlling moderate (86.7% and 88.7%) than severe (40% and 58.3%) bleeding (p=0.008 and p=0.012, respectively), and required more applications for severe (3.0±0 and 2.4±0.5) than moderate (1.7±0.8 and 1.7±0.8) bleeding control (p=0.006 and p=0.002, respectively). We observed no drug related adverse events in both groups.

INTERPRETATION: We found no significant difference between adrenaline and TXA for controlling non-catastrophic iatrogenic endobronchial bleeding after cold saline failure, adding to the body of evidence that TXA can be used safely and effectively during FB.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT04771923; URL: www.

CLINICALTRIALS: gov.

PMID:36273651 | DOI:10.1016/j.chest.2022.10.013

Pharmazie. 2022 Oct 1;77(10):299-301. doi: 10.1691/ph.2022.2408.

ABSTRACT

Medication-induced weight gain can be frustrating to patients and health care providers. Drug-induced weight gain is a profound side effect of numerous commonly used medications. The present study aimed to investigate FAERS reports about drug-induced weight gain in the last ten years. Using the US FDA Adverse Event Reporting System (FAERS) between 2012 and 2021, a retrospective, descriptive analysis was conducted to analyze the major reported Adverse Events about weight gain. During the last ten years, 137370 reports were submitted to FAERS about drug-induced weight gain. The most common drugs that are reported by the patients and that are associated with weight gain were risperidone (11.55%), adalimumab (3.94%), pregabalin (3.86%), aripiprazole (3.1%), etanercept (2.72%), and prednisone (2.70%). In conclusion, the present study showed that drug-induced weight gain is a common side effect of several medications frequently used to treat chronic diseases. Healthcare providers should educate their patients about the medicines that may cause weight gain.

PMID:36273256 | DOI:10.1691/ph.2022.2408

Syst Rev. 2022 Oct 21;11(1):227. doi: 10.1186/s13643-022-02087-z.

ABSTRACT

BACKGROUND: The early childhood development of millions of children in some low- and medium-income countries may be compromised by schistosomiasis infections contracted at the age of 5 years and below. Currently, there are no standard guidelines for treating schistosomiasis in children that are 5 years and younger using praziquantel (PZQ), the only drug that the World Health Organization (WHO) recommends for treating schistosomiasis. The review is on processes and resources involved in the treatment of schistosomiasis in children aged 5 years and below.

METHODS: An electronic search for peer-reviewed articles published in the period from January 2011 to August 2021 was done in the Academic Search Complete, CINAHL with Full Text, Health Source: Nursing/Academic Edition, and MEDLINE databases via EBSCOHost and Google Scholar databases. The search targeted journals that described the treatment of schistosomiasis in children 5 years and below using praziquantel.

RESULTS: Thirteen studies met the inclusion criteria. The patient journey for treating schistosomiasis in children aged 5 years old and below using PZQ included the following activities: enrolment of the children into the treatment program; clinical examination; diagnosis; taking anthropometric measurements; feeding the children, making the PZQ palatable to the children; administration of PZQ; and monitoring of side effects. There was also a variation in the resources used to treat children aged 5 and below for schistosomiasis.

CONCLUSIONS: A PZQ mass drug administration program for children aged 5 years old and below in endemic areas should exclude the diagnosis of schistosomiasis before treatment. The resources required in the treatment process should be affordable, and should not require skills and maintenance resources that are beyond those that are available at the primary healthcare level.

PMID:36271455 | PMC:PMC9585827 | DOI:10.1186/s13643-022-02087-z

J Bone Miner Res. 2022 Oct 21. doi: 10.1002/jbmr.4726. Online ahead of print.

ABSTRACT

Conventional therapy for hypoparathyroidism consisting of active vitamin D and calcium aims to alleviate hypocalcemia but fails to restore normal parathyroid hormone (PTH) physiology. PTH replacement therapy is the ideal physiologic treatment for hypoparathyroidism. The double-blind, placebo-controlled, 26-week, phase 3 PaTHway trial assessed the efficacy and safety of PTH replacement therapy for hypoparathyroidism individuals with the investigational drug TransCon PTH (palopegteriparatide). Participants (n=84) were randomized 3:1 to once-daily TransCon PTH (initially 18 μg/d) or placebo, both co-administered with conventional therapy. The study drug and conventional therapy were titrated according to a dosing algorithm guided by serum calcium. The composite primary efficacy endpoint was the proportion of participants at week 26 who achieved: normal albumin-adjusted serum calcium levels (8.3-10.6 mg/dL), independence from conventional therapy (requiring no active vitamin D and ≤600 mg/day of calcium), and no increase in study drug over 4 weeks prior to week 26. Other outcomes of interest included health-related quality of life measured by the 36-Item Short Form Survey (SF-36), hypoparathyroidism-related symptoms, functioning, and well-being measured by the Hypoparathyroidism Patient Experience Scale (HPES), and urinary calcium excretion. At week 26, 79% (48/61) participants treated with TransCon PTH versus 5% (1/21) placebo met the composite primary efficacy endpoint (p<0.0001). TransCon PTH treatment demonstrated a significant improvement in all key secondary endpoint HPES domain scores (all p<0.01) and the SF-36 Physical Functioning subscale score (p=0.0347) compared to placebo. Additionally, 93% (57/61) of participants treated with TransCon PTH achieved independence from conventional therapy. TransCon PTH treatment normalized mean 24-hour urine calcium. Overall, 82% (50/61) treated with TransCon PTH and 100% (21/21) placebo experienced adverse events; most were mild (46%) or moderate (46%). No study drug-related withdrawals occurred. In conclusion, TransCon PTH maintained normocalcemia while permitting independence from conventional therapy and was well-tolerated in individuals with hypoparathyroidism. This article is protected by copyright. All rights reserved.

PMID:36271471 | DOI:10.1002/jbmr.4726

J Med Case Rep. 2022 Oct 22;16(1):383. doi: 10.1186/s13256-022-03621-2.

ABSTRACT

BACKGROUND: Molecular-targeted agents used as a treatment for cancer can cause some rare and serious adverse events such as, delayed wound healing. Depending on the anticancer drug used, temporary withdrawal may be recommended before and after surgery to avoid complications. Once a surgical incision has healed and closed completely, wounds rarely open because of the initiation of molecular targeted therapy several months to years after surgery. Here, we aimed to describe a rare complication of pharyngocutaneous fistula in two patients that was thought to be caused by molecular targeted therapy.

CASE PRESENTATION: Case 1 involved a 64-year-old asian man who developed a delayed pharyngocutaneous fistula 3 months after total laryngectomy for laryngeal cancer. Ramucirumab, a vascular endothelial growth factor receptor inhibitor used for recurrent gastric cancer, was speculated to be involved. Case 2 involved a 71-year-old japanese man who developed a delayed pharyngocutaneous fistula 2 years and 1 month after total pharyngeal laryngectomy for pharyngeal cancer. It was speculated that imatinib, a platelet-derived growth factor receptor alpha inhibitor used for chronic myeloid leukemia, was involved.

CONCLUSIONS: Although the incidence of late drug-induced anastomotic leakage is very low, when it occurs, it makes oral intake impossible for an extended period and interferes with the appropriate cancer treatment. In this report, we demonstrate the details of these two patients with such a rare complication, which may help accumulate essential data on this topic.

PMID:36271412 | DOI:10.1186/s13256-022-03621-2

BMC Cancer. 2022 Oct 21;22(1):1085. doi: 10.1186/s12885-022-10174-6.

ABSTRACT

BACKGROUND: Cancer therapy has evolved from non-specific cytotoxic agents to a selective, mechanism-based approach that includes targeted agents and immunotherapy. Although the response to targeted therapies for unresectable hepatocellular carcinoma (HCC) is acceptable with the improved survival, the high tumor recurrence rate and drug-related side effects continue to be problematic. Given that immune checkpoint inhibitor alone are not robust enough to improve survival in unresectable HCC, growing evidence supports the combination of targeted therapy and immunotherapy with synergistic effect.

METHODS: Online databases including PubMed, EMBASE, Cochrane Library, and Web of Science were searched for the studies that compared targeted monotherapy with the combination therapy of targeted drug and checkpoint inhibitors in unresectable HCC patients. Eligibility criteria were the presence of at least one measurable lesion as defined by the Response Evaluation Criteria in Solid Tumors (version 1.1) for unresectable HCC patients, an Eastern Cooperative Oncology Group performance status of 0-2, and a Child-Pugh score ≤ 7. Outcome measurements include overall survival (OS), progression-free survival (PFS), and treatment-related adverse event (TRAE).

RESULTS: Three phase II/III randomized controlled trials were included in this study. The pooled results showed that combination therapy significantly improved survival than targeted monotherapy, in terms of OS (hazard ratio (HR) = 0.67; 95% confidence interval [CI]: 0.50-0.91) and PFS (HR = 0.58; 95% CI: 0.51-0.67), respectively. In the incidence of grade 3-5 TRAEs, the combination therapy was significantly higher than targeted monotherapy (odds ratio = 1.98; 95% CI: 1.13-3.48).

CONCLUSION: For unresectable HCC, combined targeted drug and immunotherapy significantly improved survival compared with targeted monotherapy. However, the incidences of AEs of combinational therapy were higher than targeted monotherapy.

PMID:36271374 | DOI:10.1186/s12885-022-10174-6

Sci Rep. 2022 Oct 21;12(1):17652. doi: 10.1038/s41598-022-22257-2.

ABSTRACT

Microscopic colitis (MC) is a chronic inflammatory bowel disease that is characterized by nonbloody watery diarrhea. The epidemiology in Japan differs from that in Europe and the United States, but little information is available from epidemiological surveys of MC in Japan. This study aimed to provide a new hypothesis regarding the factors associated with MC by using the Japanese Adverse Drug Event Report (JADER) database. "Colitis microscopic" (preferred term code: 10056979) cases entered into the JADER database between 2004 and 2021 were analyzed. Of the 246,997 cases in the JADER database, 161 cases were observed to be associated with MC. A Weibull analysis revealed that the median onset duration of MC (interquartile range) was 72.5 (36.0‒125.5) days in lansoprazole users and 116.0 (60.3‒1089.0) days in aspirin users. A multiple logistic regression analysis revealed that MC was significantly associated with the female sex, as well as ages ≥ 60 years and drugs including lansoprazole, aspirin, and nicorandil. A subset analysis revealed that MC was positively associated with obesity in female cases. Our study cannot demonstrate a causal inference between MC and each drug; however, the findings suggest that MC was associated with nicorandil as well as with lansoprazole and aspirin.

PMID:36271126 | PMC:PMC9587040 | DOI:10.1038/s41598-022-22257-2

Hum Exp Toxicol. 2022 Jan-Dec;41:9603271221136205. doi: 10.1177/09603271221136205.

ABSTRACT

The therapeutic efficacy of cisplatin (CIS) is limited owing to its hepatotoxic side effects. The current study aimed to investigate the protective impact of ferulic acid (FA) and low-doses of γ-irradiation (LDR) against CIS-prompted hepatotoxicity in rats. Adult male Swiss albino rats were divided into eight groups: untreated group; FA, LDR, and CIS treated groups; and combinations of one or more of the above treatments. Post-treatment analyses included measuring redox markers like SOD and CAT activity, NO free radical content, and lipid peroxidation in liver tissue. Serum aminotransferase activities were also determined. Additionally, gene transcript levels of liver NF-ҡB-P65, caspase-1, COX-2, and IL-1β were quantified. Moreover, immunohistochemistry for caspase-3 and histopathological examinations were estimated in liver tissue. Our findings revealed increased levels of oxidative stress along with a significant reduction in anti-oxidative responses and a significant increase in serum aminotransferase activities in the CIS-intoxicated group. A similar increase was also observed in COX-2 and IL-1β transcript levels and caspase-3 enzyme activity, besides a decrease in transcript levels of NF-ҡB-p65 and caspase-1, indicating an overall inflammatory trend and an increase in the apoptotic shift. The co-administration of FA and/or treatment with LDR has ameliorated the hepatotoxic effect induced by CIS. The histopathological investigation of liver tissues confirmed this ameliorating action of these adjuvant therapies against CIS toxicity. In conclusion, it is plausible to suggest that the hepatoprotective effects of co-administration of FA and/or LDR against CIS-induced hepatotoxicity are attributed to the possession of anti-oxidative, anti-inflammatory, and anti-apoptotic capabilities.

PMID:36270770 | DOI:10.1177/09603271221136205

Eur J Hosp Pharm. 2022 Oct 21:ejhpharm-2022-003416. doi: 10.1136/ejhpharm-2022-003416. Online ahead of print.

NO ABSTRACT

PMID:36270792 | DOI:10.1136/ejhpharm-2022-003416

Clin Oral Investig. 2022 Oct 21. doi: 10.1007/s00784-022-04717-1. Online ahead of print.

ABSTRACT

OBJECTIVES: This study evaluates the impact of systemic medications and polypharmacy on unstimulated (UWS) and chewing-stimulated whole saliva (SWS) flow rates in patients with xerostomia.

MATERIAL AND METHODS: This cross-sectional multicenter study is based on data of patients referred to five oral medicine outpatient practices in Europe and USA from January 2000 and April 2014. Relevant demographic, social, medical history and current medications were collected.

RESULTS: The study included 1144 patients, 972 (85%) females, with a mean (SD) age of 59 (14.1) years. In unmatched patients, the UWS flow rate was lower in patients taking a medication (vs. not taking a medication) from the following drug categories: opioid analgesics, anticonvulsants, antidepressants, antihypertensives, benzodiazepines, corticosteroids, diuretics, disease-modifying antirheumatic drugs (DMARDs) and hormones. There was a greater negative effect on SWS flow rate in patients taking (vs. not taking) anticonvulsants, antidepressants, benzodiazepines, corticosteroids, and DMARDs. In matched patients, both UWS (0.22 vs. 0.19 ml/min; p = 0.03) and SWS (0.97 vs. 0.85 ml/min; p = .017) flow rates were higher in patients on non-opioid analgesics (vs. not taking). The UWS flow rate was lower in patients taking antidepressants (vs. not taking) (0.16 vs. 0.22 ml/min p = .002) and higher (and within normal range) in patients taking sex hormones (vs. not taking) (0.25 vs. 0.16 ml/min; p = .005). On the other hand, SWS was lower in patients taking corticosteroid (vs. not taking) (0.76 vs. 1.07 ml/min; p = .002), and in patients taking DMARDs (vs. not taking) (0.71 vs. 0.98 ml/min; p = .021). Finally, differences in medians of both UWS and SWS were statistically significant in patients taking 1 or more than 1 opioid analgesic (vs. not taking, p ≤ .0001 and p = .031, respectively), 1 or more than 1 anticonvulsants (vs. not taking, p = .008 and p = .007), 1 or more than 1 antidepressants (vs. not taking, p < .0001 for both), 1 or more than 1 DMARDs (vs. not taking, p = .042, and p = .003).

CONCLUSIONS: A greater negative impact on UWS and SWS flow rates was seen in patients taking more than one medication from the same drug class. Intake of antidepressants, corticosteroids and DMARDs is associated with lower whole saliva flow rates.

CLINICAL RELEVANCE: Salivary flow rate can be modified by some specific medications, mostly by polypharmacy.

PMID:36269468 | DOI:10.1007/s00784-022-04717-1