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The impact of pregnancy-related hormonal and physiological changes on antiseizure medications: expert perspective. 与妊娠有关的荷尔蒙和生理变化对抗癫痫药物的影响:专家观点。
IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-01 Epub Date: 2024-05-21 DOI: 10.1080/17512433.2024.2356617
Denise Li, Susannah Franco, Page B Pennell

Introduction: Epilepsy is a disorder of recurrent, unprovoked seizures affecting approximately 15 million individuals of childbearing potential worldwide. Patients with epilepsy rely on regular daily therapy with antiseizure medications (ASMs). Furthermore, ASMs are also prescribed for other neuropsychiatric indications (e.g. bipolar disorder, pain, migraines) with over 2% of the pregnancies in the United States involving prenatal exposure to ASMs.

Areas covered: ASM concentrations are affected by hormonal and physiological changes in pregnancy, including increases in renal and hepatic blood flow, decreased protein binding, and changes in enzyme activity. Clearance changes typically reverse within a few weeks after delivery. During pregnancy, many ASMs, such as lamotrigine, levetiracetam, and oxcarbazepine, should have serum concentrations monitored and doses increased to maintain the individualized target range for seizure control. ASMs metabolized via glucuronidation, primarily lamotrigine, undergo marked increases in clearance throughout pregnancy, requiring about 3-fold the pre-pregnancy daily dose by delivery. Postpartum, ASM doses are usually decreased over several weeks to prevent drug toxicity.

Expert opinion: In the future, the development of a physiologically-based pharmacokinetic model for various ASMs may enable empiric dose adjustments in pregnancy without the difficulties of frequent therapeutic drug monitoring.

导言:癫痫是一种无诱因反复发作的疾病,影响着全球约 1500 万育龄人群。癫痫患者需要每天定期服用抗癫痫药物(ASMs)。此外,ASMs 还可用于其他神经精神适应症(如躁郁症、疼痛、偏头痛),美国有超过 2% 的孕妇在产前接触过 ASMs:ASM 的浓度受孕期激素和生理变化的影响,包括肾脏和肝脏血流量增加、蛋白结合力下降以及酶活性变化。清除率的变化通常在分娩后几周内逆转。在妊娠期间,许多 ASMs,如拉莫三嗪、左乙拉西坦和奥卡西平,应监测血清浓度并增加剂量,以维持癫痫发作控制的个体化目标范围。通过葡萄糖醛酸化代谢的 ASM(主要是拉莫三嗪)在整个孕期的清除率会显著增加,到分娩时需要的每日剂量约为孕前的 3 倍。产后,ASM 的剂量通常会在几周内减少,以防止药物中毒:专家意见:未来,针对各种 ASM 开发基于生理学的药代动力学模型可能会使妊娠期经验性剂量调整成为可能,而无需频繁进行治疗药物监测。
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引用次数: 0
Reply to: The risk for genito-urinary infections with sodium-glucose cotransporter-2 inhibitors: duration rather than dose matter? 答复:钠-葡萄糖共转运体-2 抑制剂的泌尿生殖系统感染风险:时间长短比剂量更重要?
IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-01 Epub Date: 2024-06-12 DOI: 10.1080/17512433.2024.2367101
Kannan Sridharan, Gowri Sivaramakrishnan
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引用次数: 0
Perspectives on deprescribing in older people with type 2 diabetes and/or cardiovascular conditions: challenges from healthcare provider, patient and caregiver perspective, and interventions to support a proactive approach. 对患有 2 型糖尿病和/或心血管疾病的老年人取消处方的看法:从医疗服务提供者、患者和护理者的角度看所面临的挑战,以及支持积极主动方法的干预措施。
IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-01 Epub Date: 2024-08-12 DOI: 10.1080/17512433.2024.2378765
Petra Denig, Peter J C Stuijt

Introduction: For people with type 2 diabetes and/or cardiovascular conditions, deprescribing of glucose-lowering, blood pressure-lowering and/or lipid-lowering medication is recommended when they age, and their health status deteriorates. So far, deprescribing rates of these so-called cardiometabolic medications are low. A review of challenges and interventions addressing these challenges in this population is pertinent.

Areas covered: We first provide an overview of relevant deprescribing recommendations. Next, we review challenges for healthcare providers (HCPs) to deprescribe cardiometabolic medication and provide insight in the patient and caregiver perspective on deprescribing. We summarize findings from research on implementing deprescribing of cardiometabolic medication and reflect on strategies to enhance deprescribing. We have used a combination of methods to search for relevant articles.

Expert opinion: There is a need for rigorous development and evaluation of intervention strategies aimed at proactive deprescribing of cardiometabolic medication. To address challenges at different levels, these should be multifaceted interventions. All stakeholders must become aware of the relevance of deintensifying medication in this population. Education and training for HCPs and patients should support patient-centered communication and shared decision-making. Development of procedures and tools to select eligible patients and conduct targeted medication reviews are important for implementation of deprescribing in routine care.

导言:对于 2 型糖尿病和/或心血管疾病患者来说,当他们年龄增长、健康状况恶化时,建议他们停用降糖、降压和/或降脂药物。迄今为止,这些所谓的心血管代谢药物的停药率很低。对这一人群所面临的挑战和应对这些挑战的干预措施进行回顾很有意义:我们首先概述了相关的取消处方建议。接下来,我们回顾了医疗服务提供者(HCPs)在开具心脏代谢药物处方时所面临的挑战,并从患者和护理人员的角度深入分析了开具处方的问题。我们总结了有关实施心脏代谢药物去处方化的研究结果,并思考了加强去处方化的策略。我们采用了多种方法搜索相关文章:专家观点:有必要严格制定和评估旨在主动取消心脏代谢药物处方的干预策略。为了应对不同层面的挑战,这些干预措施应该是多方面的。所有利益相关者都必须认识到对这一人群减量用药的意义。针对保健医生和患者的教育和培训应支持以患者为中心的沟通和共同决策。开发相关程序和工具以选择符合条件的患者并进行有针对性的药物审查,对于在常规护理中实施减量用药非常重要。
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引用次数: 0
Lipid profile changes induced by glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes: a systematic review and network meta-analysis. 胰高血糖素样肽-1 受体激动剂诱导的 2 型糖尿病患者血脂变化:系统综述和网络荟萃分析。
IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-01 Epub Date: 2024-06-06 DOI: 10.1080/17512433.2024.2363838
Yuna Chae, Sun-Hong Kwon, Jin Hyun Nam, Eunsung Kang, Jiae Im, Hyo-Jin Kim, Eui-Kyung Lee

Objective: This study was conducted to investigate the effects of glucagon-like peptide-1 receptor (GLP-1) agonists on the lipid profiles of patients with type 2 diabetes.

Methods: We retrieved the data of phase 3 randomized controlled trials on GLP-1 agonists in patients with type 2 diabetes from the PubMed, Embase, and Cochrane library up to 11 February 2024. We extracted % changes in low-density lipoprotein cholesterol (LDL-C)/high-density lipoprotein cholesterol/total cholesterol (T-CHO) and triglycerides levels from baseline. Using Bayesian network meta-analysis, mean differences and 95% credible intervals for lipid changes were estimated as a unit of percentage points (%p) by class.

Results: Twenty-six studies covering 22,290 participants were included. The glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 dual agonist showed significant differences in LDL-C (range of mean differences: -11.61 to -6.77%p), triglycerides (-19.94 to -13.31%p), and T-CHO (-7.94 to -5.09%p) levels compared to placebo, insulin, and sodium-glucose co-transporter 2 (SGLT2) inhibitors. The GLP-1 agonist significantly reduced T-CHO (-5.20%p; -6.39%p) and LDL-C (-4.32%p; -8.17%p) levels compared to placebo and SGLT2 inhibitors, respectively.

Conclusions: The GIP/GLP-1 dual agonist positively affects the lipid profiles of patients with type 2 diabetes. This may contribute to a lower risk of cardiovascular disease in patients with type 2 diabetes.

Protocol registration: PROSPERO (CRD42021282668).

研究目的本研究旨在探讨胰高血糖素样肽-1受体(GLP-1)激动剂对2型糖尿病患者血脂状况的影响:我们从 PubMed、Embase 和 Cochrane 图书馆检索了截至 2024 年 2 月 11 日有关 GLP-1 激动剂治疗 2 型糖尿病患者的 3 期随机对照试验数据。我们提取了低密度脂蛋白胆固醇(LDL-C)/高密度脂蛋白胆固醇/总胆固醇(T-CHO)和甘油三酯水平与基线相比的变化百分比。采用贝叶斯网络荟萃分析法,以百分点(%p)为单位,按等级估算血脂变化的平均差异和 95% 可信区间:共纳入 26 项研究,覆盖 22,290 名参与者。与安慰剂、胰岛素和钠-葡萄糖协同转运体 2(SGLT2)抑制剂相比,葡萄糖依赖性胰岛素多肽(GIP)/GLP-1 双激动剂在低密度脂蛋白胆固醇(-11.61% 至 -6.77%p)、甘油三酯(-19.94% 至 -13.31%p)和 T-CHO (-7.94% 至 -5.09%p)水平上有显著差异。与安慰剂和SGLT2抑制剂相比,GLP1激动剂能显著降低T-CHO(-5.20%p;-6.39%p)和LDL-C(-4.32%p;-8.17%p)水平:GIP/GLP-1双重激动剂对2型糖尿病患者的血脂状况有积极影响。结论:GIP/GLP-1 双激动剂对 2 型糖尿病患者的血脂状况有积极影响,这可能会降低罹患心血管疾病的风险:prospero(CRD42021282668)。
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引用次数: 0
Pharmacological management of testosterone deficiency in men current advances and future directions. 男性睾酮缺乏症的药物治疗当前进展和未来方向。
IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-01 Epub Date: 2024-06-13 DOI: 10.1080/17512433.2024.2366505
Giovanni Corona, Giulia Rastrelli, Clotilde Sparano, Linda Vignozzi, Alessandra Sforza, Mario Maggi

Introduction: Testosterone deficiency (TD) is relatively common in aging men, affecting around 2% of the general population. Testosterone replacement therapy (TRT) represents the most common medical approach for subjects who are not interested in fathering.

Areas covered: This review summarizes advances in TRT, including approved or non-approved pharmacological options to overcome TD. When possible, a meta-analytic approach was applied to minimize subjective and biased interpretations of the available data.

Expert opinion: During the last decade, several new TRT formulations have been introduced on the market, including oral, transdermal, and parenteral formulations. Possible advantages and limitations have been discussed appropriately. Anti-estrogens, including selective estrogen modulators or aromatase inhibitors still represent further possible off-label options. However, long-term side effects on sexual function and bone parameters constitute major limitations. Glucagon-like peptide 1 analogues can be an alternative option in particular for massive obesity-associated TD. Weight loss obtained through lifestyle modifications including diet and physical exercise should be encouraged in all overweight and obese patients. A combination of TRT and lifestyle changes can be considered in those subjects in whom a reversal of the condition cannot be expected in a reasonable time frame.

简介睾酮缺乏症(TD)在老年男性中较为常见,约占总人口的 2%。睾酮替代疗法(TRT)是针对无意成为父亲的受试者最常用的医疗方法:本综述总结了睾丸激素替代疗法的进展,包括已获批准或未获批准的克服睾丸发育迟缓的药物疗法。在可能的情况下,采用了荟萃分析法,以尽量减少对现有数据的主观和偏颇解释:过去十年间,市场上出现了几种新的TRT制剂,包括口服、透皮和肠外制剂。对其可能的优势和局限性进行了适当的讨论。抗雌激素类药物,包括选择性雌激素调节剂或芳香化酶抑制剂仍是可能的标签外选择。然而,对性功能和骨骼参数的长期副作用是主要限制因素。胰高血糖素样肽 1 类似物是一种替代选择,尤其适用于与肥胖相关的大量 TD。应鼓励所有超重和肥胖患者通过改变生活方式(包括饮食和体育锻炼)来减轻体重。对于那些无法在合理时间内逆转病情的患者,可以考虑将 TRT 和改变生活方式相结合。
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引用次数: 0
CSL112 and HDL function hypothesis - a never-ending wait. CSL112 和高密度脂蛋白功能假说--永无止境的等待。
IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-01 Epub Date: 2024-07-15 DOI: 10.1080/17512433.2024.2378763
Muhammad Adnan Zaman, Sidra Kalsoom, Warsha Koran
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引用次数: 0
Clinical considerations when switching antiretroviral therapy. 转换抗逆转录病毒疗法时的临床考虑因素。
IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-07-01 Epub Date: 2024-06-17 DOI: 10.1080/17512433.2024.2365826
Analuz Fernández, Arkaitz Imaz

Introduction: Antiretroviral therapy (ART) can be personalized through simple formulations with high resistance barriers, favorable safety profiles, and novel administration routes. Switching treatments has become a key clinical strategy for addressing drug toxicity and interactions and enhancing adherence and convenience. This strategy aims to improve the quality of life and long-term efficacy, even in challenging cases like people living with HIV (PLWH) with multiple comorbidities, prior virological failure, and drug resistance.

Areas covered: The authors reviewed clinical trials and cohort studies providing evidence of benefits and risks of current antiretroviral (ARV) drugs as switching options for PLWH in various scenarios. The literature search included clinical trials, meta-analyses, observational studies, and review articles in English published after 2000, and current HIV treatment guidelines in English and Spanish as of February 2024.

Expert opinion: New ARV drugs offer advantages in efficacy and safety over previous options but may also have adverse effects. Second-generation integrase inhibitors and tenofovir alafenamide show benefits as switching options in various scenarios, though more research is needed on potential weight gain and metabolic issues. Injectable long-acting ART is promising for switching strategies, but finding the optimal combination of new drugs remains challenging.

导言:抗逆转录病毒疗法(ART)可以通过具有高耐药性屏障、良好的安全性和新型给药途径的简单制剂实现个性化治疗。转换疗法已成为解决药物毒性和相互作用、提高依从性和便利性的关键临床策略。这一策略旨在提高生活质量和长期疗效,即使是对具有多种并发症、既往病毒学失败和耐药性的艾滋病病毒感染者(PLWH)等具有挑战性的病例也是如此:作者对临床试验和队列研究进行了综述,这些研究提供了当前抗逆转录病毒(ARV)药物在不同情况下作为 PLWH 转药选择的益处和风险证据。文献检索包括 2000 年之后发表的英文临床试验、荟萃分析、观察性研究和综述文章,以及截至 2024 年 2 月的英文和西班牙文现行 HIV 治疗指南:新的抗逆转录病毒药物在疗效和安全性方面均优于以往的选择,但也可能存在不良反应。第二代整合酶抑制剂和替诺福韦-阿拉非那胺显示出在各种情况下作为转换方案的优势,但还需要对潜在的体重增加和代谢问题进行更多研究。注射用长效抗逆转录病毒疗法在转换策略中大有可为,但找到新药的最佳组合仍具有挑战性。
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引用次数: 0
Antiretroviral therapy response: exploring the potential influence of SARS-CoV-2. 抗逆转录病毒疗法反应:探索 SARS-CoV-2 的潜在影响。
IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-07-01 Epub Date: 2024-02-28 DOI: 10.1080/17512433.2024.2322984
Ahmad Z Al Meslamani
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引用次数: 0
Therapeutic drug monitoring of antiretroviral therapy: current progresses and future directions. 抗逆转录病毒疗法的治疗药物监测:当前进展和未来方向。
IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-07-01 Epub Date: 2024-06-04 DOI: 10.1080/17512433.2024.2363847
Dario Cattaneo, Cristina Gervasoni

Introduction: The treatment of HIV infection has been revolutionized in recent years thanks to the advent of dual antiretroviral regimens, administered orally or as long-acting injectable formulations. Here, we provide an update on the usefulness of therapeutic drug monitoring (TDM) of antiretroviral drugs to optimize the management of people with HIV (PWH) in the current scenario.

Areas covered: A MEDLINE PubMed search for articles published between January 2014 and January 2024 was completed matching the terms HIV, antiretrovirals and TDM. Moreover, additional studies were identified from the reference list of retrieved articles.

Expert opinion: Available antiretroviral treatments achieve a response rate of 90%-95%, making the routine TDM of antiretroviral drugs of limited clinical value. However, there are still some important applications of TDM in selected clinical conditions, such as assessing patient compliance or suspected drug-drug interactions (DDIs). Indeed, we are increasingly having to deal with polypharmacy and DDIs in the context of an aging patient with comorbidities that may potentially alter the pharmacokinetics of antiretroviral drugs. Finally, the role of pharmacogenetics, which is closely related to TDM, in influencing both the disposition of antiretrovirals and the course of DDIs should also be considered.

导言:近年来,由于出现了口服或长效注射的双重抗逆转录病毒疗法,艾滋病病毒感染的治疗发生了革命性的变化。在此,我们将介绍抗逆转录病毒药物治疗药物监测(TDM)的最新进展,以优化当前情况下对艾滋病病毒感染者(PWH)的管理:对 2014 年 1 月至 2024 年 1 月期间发表的文章进行了 MEDLINE PubMed 搜索,搜索关键词为 HIV、抗逆转录病毒药物、TDM。此外,还从检索文章的参考文献列表中发现了其他研究:专家意见:现有的抗逆转录病毒治疗可达到 90%-95% 的应答率,因此抗逆转录病毒药物的常规 TDM 临床价值有限。不过,TDM 在某些特定的临床条件下仍有一些重要的应用,如评估患者的依从性或可疑的药物相互作用(DDI)。事实上,我们越来越多地需要在高龄患者合并症的背景下处理多重用药和 DDIs 问题,这些合并症可能会改变抗逆转录病毒药物的药代动力学。最后,还应考虑与药物代谢动力学密切相关的药物遗传学在影响抗逆转录病毒药物的处置和 DDIs 过程中的作用。
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引用次数: 0
Considerations when prescribing opioid agonist therapies for people living with HIV. 为艾滋病毒感染者开具阿片类激动剂疗法处方时的注意事项。
IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-07-01 Epub Date: 2024-07-04 DOI: 10.1080/17512433.2024.2375448
Adati Tarfa, Audun J Lier, Sheela V Shenoi, Sandra A Springer

Introduction: Medications for opioid use disorder (MOUD) include opioid agonist therapies (OAT) (buprenorphine and methadone), and opioid antagonists (extended-release naltrexone). All forms of MOUD improve opioid use disorder (OUD) and HIV outcomes. However, the integration of services for HIV and OUD remains inadequate. Persistent barriers to accessing MOUD underscore the immediate necessity of addressing pharmacoequity in the treatment of OUD in persons with HIV (PWH).

Areas covered: In this review article, we specifically focus on OAT among PWH, as it is the most commonly utilized form of MOUD. Specifically, we delineate the intersection of HIV and OUD services, emphasizing their integration into the United States Ending the HIV Epidemic (EHE) plan by offering comprehensive screening, testing, and treatment for both HIV and OUD. We identify potential drug interactions of OAT with antiretroviral therapy (ART), address disparities in OAT access, and present the practical benefits of long-acting formulations of buprenorphine, ART, and pre-exposure prophylaxis for improving HIV prevention and treatment and OUD management.

Expert opinion: Optimizing OUD outcomes in PWH necessitates careful attention to diagnosing OUD, initiating OUD treatment, and ensuring medication retention. Innovative approaches to healthcare delivery, such as mobile pharmacies, can integrate both OUD and HIV and reach underserved populations.

导言:治疗阿片类药物使用障碍(MOUD)的药物包括阿片类药物激动剂疗法(OAT)(丁丙诺啡和美沙酮)和阿片类药物拮抗剂(缓释纳曲酮)。所有形式的 MOUD 都能改善阿片类药物使用障碍(OUD)和艾滋病的治疗效果。然而,针对艾滋病毒和阿片类药物使用障碍的整合服务仍然不足。在获得 MOUD 方面持续存在的障碍凸显了在治疗艾滋病病毒感染者(PWH)的 OUD 时解决药物公平性问题的紧迫性:在这篇综述文章中,我们特别关注艾滋病感染者中的 OAT,因为它是最常用的 MOUD 形式。具体而言,我们描述了艾滋病和 OUD 服务的交叉点,强调通过提供全面的艾滋病和 OUD 筛查、检测和治疗,将其纳入美国遏制艾滋病流行(EHE)计划。我们确定了 OAT 与抗逆转录病毒疗法(ART)之间潜在的药物相互作用,解决了 OAT 获取方面的差异,并介绍了丁丙诺啡长效制剂、抗逆转录病毒疗法和暴露前预防对改善 HIV 预防和治疗以及 OUD 管理的实际益处:专家意见:要优化公共卫生机构的 OUD 治疗效果,就必须认真关注 OUD 的诊断、OUD 治疗的启动以及药物的保留。创新的医疗保健服务方式(如流动药房)可以将 OUD 和 HIV 治疗结合起来,并惠及服务不足的人群。
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引用次数: 0
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Expert Review of Clinical Pharmacology
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