Mercedes Malone, Abdelilah Lahmar, Atif Siddique, Michael Rozboril, Jesse L Kresak
Elevated lipid panels are associated with an increased risk of cardiovascular disease. Management of heart disease with lipid lowering agents play a vital role in medicine. Statins are one group of medications that are widely utilized in the medical field to decrease the risk of atherosclerotic disease. Statins work by inhibiting the hepatic enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). Although statins are one of the most effective drugs for secondary and primary prevention of heart disease, they are not without risks and side effects such as hepatotoxicity and myopathy...
2023: Journal of Primary Care & Community Health
Jean-Sébastien Wattez, Elodie Eury, Bethany C Hazen, Alexa Wade, Sarah Chau, Shu-Ching Ou, Aaron P Russell, Yoshitake Cho, Anastasia Kralli
OBJECTIVE: Skeletal muscle oxidative capacity is central to physical activity, exercise capacity and whole-body metabolism. The three estrogen related receptors (ERRs) are regulators of oxidative metabolism in many cell types, yet their roles in skeletal muscle remain unclear. The main aim of this study was to compare the relative contributions of ERRs to oxidative capacity in glycolytic and oxidative muscle, and to determine defects associated with loss of skeletal muscle ERR function...
January 13, 2023: Molecular Metabolism
Vietxuan Phan, Denisa Hathazi, Corinna Preuße, Artur Czech, Erik Freier, Gerta Shema, René Zahedi, Andreas Roos
OBJECTIVES: Chloroquine (CQ) is an antimalarial drug with a growing number of applications as recently demonstrated in attempts to treat Covid-19. For decades, it has been well-known that skeletal and cardiac muscle cells might display vulnerability against CQ exposure resulting in the clinical manifestation of a CQ-induced myopathy. In line with the known effect of CQ on inhibition of the lysosomal function and thus cellular protein clearance, the build-up of autophagic vacuoles along with protein aggregates is a histological hallmark of the disease...
January 12, 2023: Neuropathology and Applied Neurobiology
Braulio Valdebenito-Maturana, Franco Valdebenito-Maturana, Mónica Carrasco, Juan Carlos Tapia, Alejandro Maureira
High cholesterol levels have been linked to a high risk of cardiovascular diseases, and preventative pharmacological care to lower cholesterol levels is critically important. Statins, which are hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, are drugs used to reduce the endogenous cholesterol synthesis, thus minimizing its pathophysiological effects. Despite the proven benefits, statins therapy is known to cause a number of skeletal muscle disorders, including myalgia, myopathy and myositis...
December 23, 2022: International Journal of Molecular Sciences
Wann Jia Loh, Gerald F Watts
PURPOSE OF REVIEW: We describe and discuss the safety of statins and non-statin drugs in neuromuscular disorders (NMDs). We also propose a pragmatic model of care for the management of such cases. RECENT FINDINGS: Patients with both NMD and hypercholesterolemia may be particularly disadvantaged owing to the toxic effects of cholesterol-lowering therapy and the inability to take medication. Specifically, the management of hypercholesterolemia in patients with NMD is complicated by the increased risk of statin-related myotoxicity and concerns that statins may aggravate or possibly induce the onset of a specific NMD...
January 7, 2023: Current Atherosclerosis Reports
Ting Deng, Tong Zhang, Haitao Lu, Jingmian Chen, Xiaomeng Liu, Wei He, Xiaohua Yao
OBJECTIVES: We investigated the efficacy of intensive rosuvastatin therapy plus 7-day dual antiplatelet therapy (DAPT) in reducing stroke recurrence for patients with acute ischemic stroke (AIS) and compared subgroups of patients. METHODS: We enrolled patients with AIS whose time of onset to medication was ≤ 72 h, and the baseline scores of NIHSS (bNIHSS) were 0-10. The patients received intensive rosuvastatin therapy plus 7-day DAPT with aspirin and clopidogrel (study group) or rosuvastatin plus single antiplatelet therapy (SAPT, control group)...
December 29, 2022: European Journal of Clinical Pharmacology
Emanuel José Saad, Andrés Rodríguez Ruiz, Augusto Douthat Y Barrionuevo, Martín Milanesio, Janet Flores Balverdi, Nadia Claudine Riscanevo, Gabriela Estefanía Peñaranda, Elisa Beatriz Novatti, Verónica Saurit, Ana Cecilia Alvarez, Diego Federico Baenas
INTRODUCTION: HyperCKemia is defined as the elevation of creatine phosphokinase (CK) levels greater than 1.5 times the upper limit (CK>285 U/L), being produced by multiple causes, which vary according different populations. The main objective of the study was to know the frequency of hyperCKemia in two hospitals in Córdoba and its main causes. METHODS: Retrospective analytical study in two hospitals in Córdoba, Argentina, where all patients over 18 years of age who presented CK values ​​greater than 285 U/L on at least 2 occasions in a period between 1 and 4 weeks were identified, between the years 2015 and 2017...
December 21, 2022: Revista de la Facultad de Ciencias Médicas
Natasha Ranu, Jenni Laitila, Hannah F Dugdale, Jennifer Mariano, Justin S Kolb, Carina Wallgren-Pettersson, Nanna Witting, John Vissing, Juan Jesus Vilchez, Chiara Fiorillo, Edmar Zanoteli, Mari Auranen, Manu Jokela, Giorgio Tasca, Kristl G Claeys, Nicol C Voermans, Johanna Palmio, Sanna Huovinen, Maurizio Moggio, Thomas Nyegaard Beck, Aikaterini Kontrogianni-Konstantopoulos, Henk Granzier, Julien Ochala
Nemaline myopathy (NM) is one of the most common non-dystrophic genetic muscle disorders. NM is often associated with mutations in the NEB gene. Even though the exact NEB-NM pathophysiological mechanisms remain unclear, histological analyses of patients' muscle biopsies often reveal unexplained accumulation of glycogen and abnormally shaped mitochondria. Hence, the aim of the present study was to define the exact molecular and cellular cascade of events that would lead to potential changes in muscle energetics in NEB-NM...
December 17, 2022: Acta Neuropathologica Communications
Tim McEwan, Jaspreet Bhambra, David F Liew, Philip C Robinson
OBJECTIVE: To identify reports of colchicine-induced neuropathy and myopathy and ascertain risk factors associated with this toxicity at commonly used doses. METHODS: A systematic review of case reports was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA methodology). PubMed and EMBASE were searched through October 2021 for case reports of neuropathy and/or myopathy associated with the use of colchicine at therapeutic doses...
December 8, 2022: Seminars in Arthritis and Rheumatism
Takashi Murayama, Nagomi Kurebayashi, Takuro Numaga-Tomita, Takuya Kobayashi, Satoru Okazaki, Kyosuke Yamashiro, Tsutomu Nakada, Shuichi Mori, Ryosuke Ishida, Hiroyuki Kagechika, Mitsuhiko Yamada, Takashi Sakurai
In skeletal muscle excitation-contraction (E-C) coupling, depolarization of the plasma membrane triggers Ca2+ release from the sarcoplasmic reticulum (SR), referred to as depolarization-induced Ca2+ release (DICR). DICR occurs through the type 1 ryanodine receptor (RyR1), which physically interacts with the dihydropyridine receptor Cav1.1 subunit in specific machinery formed with additional essential components including β1a, Stac3 adaptor protein, and junctophilins. Exome sequencing has accelerated the discovery of many novel mutations in genes encoding DICR machinery in various skeletal muscle diseases...
December 5, 2022: Journal of General Physiology
Javier Reig-López, Matilde Merino-Sanjuan, Alfredo García-Arieta, Victor Mangas-Sanjuán
Atorvastatin is the most prescribed 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor used to lower cardiovascular risk and constitutes one of the best-selling drugs world-wide. Several physiologically based pharmacokinetic (PBPK) models have been developed to assess its non-straightforward pharmacokinetics (PK) as well as that of its metabolites and have been only applied to assess drug-drug interactions (DDI). Here we present a full PBPK model for atorvastatin and its metabolites able to predict within a 2-fold error their PK after the administration of a solid oral dosage form containing the calcium salt of atorvastatin in single and multiple dosing schedules at 20, 40, and 80 mg and 10 mg dose levels, respectively...
October 26, 2022: Biomedicine & Pharmacotherapy
Yuqi Si, Fenli Su, Haoxiang Wu, Chuangpeng Shen
Anti-thyroid drugs (ATDs), such as methimazole (MMI) and propylthiouracil (PTU), are the most common treatment options for hyperthyroidism. Although effective, well-known adverse effects include agranulocytosis, toxic hepatitis, vasculitis, and arthralgias. Myalgia and elevation of serum creatine kinase (CK) are relatively rare, with an unclear mechanism. Rapid decrease in the thyroid hormone level may be associated with ATD-related myopathy; however, direct effects of the drug on muscle tissue cannot be excluded...
September 2, 2022: International Journal of Clinical Pharmacology and Therapeutics
Mohammed Dashti, Abdullah Al-Matrouk, Arshad Channanath, Fahd Al-Mulla, Thangavel Alphonse Thanaraj
Organic anion transporting polypeptides (OATP), which are encoded by SLCO genes, participate in the hepatic elimination of drugs and xenobiotics. SLCO1B1 is an important pharmacogenomic gene (encoding OATP1B1) associated with response to the uptake of endogenous compounds, such as statin and bilirubin. Ethnicity of the patient modulates the response to these drugs; the frequency and haplotype data for SLCO1B1 genetic variants in the Arab population is lacking. Therefore, we determined the frequencies of two well-characterized SLCO1B1 single nucleotide polymorphisms (SNP) and haplotypes that affect the OATP1B1 drugs transportation activity in Qatari population...
September 1, 2022: Scientific Reports
Silvia Attardo, Olimpia Musumeci, Daniele Velardo, Antonio Toscano
Statins are drugs widely prescribed in high-risk patients for cerebrovascular or cardiovascular diseases and are, usually, safe and well tolerated. However, these drugs sometimes may cause neuromuscular side effects that represent about two-third of all adverse events. Muscle-related adverse events include cramps, myalgia, weakness, immune-mediated necrotizing myopathy and, more rarely, rhabdomyolysis. Moreover, they may lead to peripheral neuropathy and induce or unmask a preexisting neuromuscular junction dysfunction...
July 28, 2022: International Journal of Molecular Sciences
Shalini Bhaskar, Mohammed Fauzi Bin Abdul Rani
Introduction: Muscle-specific tyrosine kinase (MuSK) antibody positive myasthenia gravis (MuSK-MG) is a rare clinical disorder, and diagnosing it can be challenging. Most of the patients present with predominant facial, oculo-bulbar, and neck muscle weakness along with respiratory muscle involvement. Such a presentation can be mistaken for bulbar onset motor neuron disease or as one of the rare oculopharyngeal myopathies. Case Report . We present a young female patient, who reported to us with neck muscle weakness, ocular and bulbar muscle paralysis, and breathing difficulty...
2022: Case Reports in Medicine
F Wang, S Li, T Y Wang, G A Lopez, I Antoshechkin, T F Chou
Mutations in p97/VCP cause two motor neuron diseases: inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia and familial amyotrophic lateral sclerosis. How p97 mutations lead to motor neuron degeneration is, however, unknown. Here we used patient-derived induced pluripotent stem cells to generate p97 mutant motor neurons. We reduced the genetic background variation by comparing mutant motor neurons to its isogenic wild type lines. Proteomic analysis reveals that p97R155H/+ motor neurons upregulate several cell cycle proteins at Day 14, but this effect diminishes by Day 20...
2022: Brain communications
Leo Tsui, Peiying Ye, Shiling Xu, Yuan Lin, Bin Chen, Sy-Ping Chen, Ruoh-Yi Cheng
BACKGROUND: The baseline incidence of the adverse events of statin therapy varies between countries. Notably, Chinese patients seem more susceptible to myopathy induced by simvastatin. OBJECTIVES: This research studies the adverse drug reactions (ADRs) of statin therapy in China by analysing trial-based data from the Anti-hyperlipidaemic Drug Database built by the China National Medical Products Administration Information Centre. METHODS: All clinical trials involving statin therapy (including simvastatin, atorvastatin, fluvastatin, lovastatin, pravastatin and rosuvastatin) in China from 1989 to 2019 were screened...
June 21, 2022: European Journal of Hospital Pharmacy. Science and Practice
Siamak Moghadam-Kia, Chester V Oddis
As treatment of refractory idiopathic inflammatory myopathies (IIM) has been challenging, there is growing interest in assessing new therapies that target various pathways implicated in the pathogenesis of IIM. In the largest clinical trial to date, rituximab was studied in adult and juvenile myositis, but the primary outcome was not met despite 83 percent of subjects with refractory myositis meeting the definition of improvement. The U.S. Food and Drug Administration (FDA) has recently granted approval to Octagam 10% immune globulin intravenous (IVIg), for the treatment of adult dermatomyositis based on impressive results from a double-blind placebo-controlled trial...
August 2022: Current Opinion in Pharmacology
Keisuke Takada, Yukiyoshi Sada, Masaru Samura, Masashi Matsuura, Naoki Hirose, Takenori Kurata, Fumio Nagumo, Junichi Ishii, Sakura Koshioka, Masaki Uchida, Junki Inoue, Koji Tanikawa, Hiroyuki Kunishima
BACKGROUND Rhabdomyolysis is a condition in which intracellular components are released into the blood and urine. Rhabdomyolysis can be caused by drug-related complications and COVID-19; however, the underlying mechanism is not clear. In this study, we report a case of rhabdomyolysis complicated by COVID-19, in which we presumed that the cause of rhabdomyolysis was related to prior administration of haloperidol by assessment of the drug history and progression of myopathy. CASE REPORT A 52-year-old man with schizophrenia experienced worsening insomnia 10 days before admission...
June 20, 2022: American Journal of Case Reports
Chris Lindsay, Maria Musgaard, Angela J Russell, Rebecca Sitsapesan
BACKGROUND AND PURPOSE: Statins, inhibitors of HMG-CoA reductase, are mainstay treatment for hypercholesterolemia. However, muscle pain and weakness prevent many patients from benefiting from their cardioprotective effects. We previously demonstrated that simvastatin activates skeletal ryanodine receptors (RyR1), an effect that could be important in initiating myopathy. We therefore investigated if RyR1 activation is a standard property of commonly-prescribed statins. Using a range of structurally-diverse statin analogues we examined structural features associated with RyR1 activation, aiming to identify statins lacking this property...
June 15, 2022: British Journal of Pharmacology
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