Jürgen Steinmeyer, Johannes Flechtenmacher
Differential diagnosis of muscle pain and weakness is extensive, including neurological, vertebral, arthrogenic, vascular, traumatic, immunological, endocrine, genetic and infectious aetiologies, as well as medication or toxin-related causes. Muscles are highly sensitive to a large number of drugs, especially with high doses. Although many drug classes can cause toxic myopathy, a significant number of cases are caused by lipid-lowering drugs, long-term use of corticosteroids, and, most often, alcohol misuse...
July 28, 2021: Zeitschrift Für Orthopädie und Unfallchirurgie
Ravindra Nikalji, Suvadeep Sen
Rosuvastatin is a recently approved statin and used widely across the globe for primary and secondary prevention of atherosclerotic cardiovascular heart disease. It has the highest lipid-lowering property among all statins and relatively well tolerated. Rhabdomyolysis is a rare but potentially serious adverse effect. The present report highlights the case of a patient admitted with proximal myopathy with severe rhabdomyolysis and acute kidney injury associated with life-threatening hyperkalemia. The symptoms appeared within 1 month of starting rosuvastatin...
March 2021: Indian Journal of Nephrology
Tadej Petreski, Nejc Piko, Timotej Petrijan, Benjamin Dvoršak, Radovan Hojs, Sebastjan Bevc
Statins or 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors are a mainstay of cardiovascular disease therapy. In addition to their lipid-lowering capabilities, they exhibit several pleiotropic effects. Their adverse reactions such as myalgias are not uncommon, but in rare cases, the resulting rhabdomyolysis can be fatal. Recently, more insight has been brought into the pathogenesis of statin-induced rhabdomyolysis, and immune-mediated necrotizing myopathies are diagnosed more frequently. We present a case of a female patient who was on chronic rosuvastatin therapy and developed necrotizing myopathy...
May 2021: Case Reports in Nephrology and Dialysis
Niamh O'Donnell, Aisling McCarthy, Ken Thong
Summary: Carbimazole is a commonly used antithyroid drug (ATD), which is associated with several well-established side effects. However, Carbimazole-induced rhabdomyolysis is rarely reported in the literature. We report a 27-year-old male who presented with upper limb myalgia and significantly raised creatine kinase elevation, 1-month post commencement of Carbimazole for Graves' disease. Carbimazole was ceased with subsequent clinical and biochemical improvement. Though the pathophysiology remains unclear, we hope to raise awareness regarding this rare adverse effect with a view to promote early recognition and prompt discontinuation of the offending medication caused by a commonly used medication in endocrinology...
July 1, 2021: Endocrinology, Diabetes & Metabolism Case Reports
Brian Lu, Laura Sun, Manuel Seraydarian, Thomas J Hoffmann, Marisa W Medina, Carlos Iribarren, Ronald M Krauss, Neil Risch, Akinyemi Oni-Orisan
The association between the c.521T>C variant allele in SLCO1B1 (rs4149056) and simvastatin-induced myotoxicity was discovered over a decade ago; however, whether this relationship represents a class effect is still not fully known. The aim of this study was to investigate the relationship between rs4149056 genotype and statin-induced myotoxicity in patients taking atorvastatin and lovastatin. Study participants were from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort. A total of 233 statin-induced myopathy + rhabdomyolysis cases met the criteria for inclusion and were matched to 2,342 controls...
June 11, 2021: Clinical Pharmacology and Therapeutics
Chrysoula Boutari, Asterios Karagiannis, Vasilios G Athyros
Introduction : Statins are powerful lipid-lowering agents which reduce cardiovascular (CV)-related morbidity and mortality. However, a large proportion of patients cannot attain the target low density lipoprotein cholesterol (LDL-C) levels, despite receiving maximally tolerated doses of high intensity statins. Also, adherence to treatment may be reduced due to statin-induced myopathy or other side effects. For these reasons, guidelines recommend adding the cholesterol absorption inhibitor ezetimibe. Areas covered : Authors discuss the main pharmacological characteristics of rosuvastatin and ezetimibe, their lipid-lowering and pleiotropic effects, as well as the clinical effects of the fixed dose combination of these drugs when used to treat dyslipidemia...
June 8, 2021: Expert Review of Cardiovascular Therapy
Magda Dubińska-Magiera, Marta Migocka-Patrzałek, Damian Lewandowski, Małgorzata Daczewska, Krzysztof Jagla
Drug-induced myopathies are classified as acquired myopathies caused by exogenous factors. These pathological conditions develop in patients without muscle disease and are triggered by a variety of medicaments, including lipid-lowering drugs (LLDs) such as statins, fibrates, and ezetimibe. Here we summarise the current knowledge gained via studies conducted using various models, such as cell lines and mammalian models, and compare them with the results obtained in zebrafish ( Danio rerio ) studies. Zebrafish have proven to be an excellent research tool for studying dyslipidaemias as a model of these pathological conditions...
May 26, 2021: International Journal of Molecular Sciences
Ester Zito, Ana Ferreiro
Selenoprotein N (SEPN1) is a type II glycoprotein of the endoplasmic reticulum (ER) that senses calcium levels to tune the activity of the sarcoplasmic reticulum calcium pump (SERCA pump) through a redox-mediated mechanism, modulating ER calcium homeostasis. In SEPN1-depleted muscles, altered ER calcium homeostasis triggers ER stress, which induces CHOP-mediated malfunction, altering excitation-contraction coupling. SEPN1 is localized in a region of the ER where the latter is in close contact with mitochondria, i...
May 6, 2021: Cells
Francesco Bruno, Rosa Antonietta Palmiero, Bruno Ferrero, Federica Franchino, Alessia Pellerino, Enrica Milanesi, Riccardo Soffietti, Roberta Rudà
Introduction: Anti-PD1 agents are widely used in the treatment of solid tumors. This has prompted the recognition of a class of immune-related adverse events (irAEs), due to the activation of autoimmune T-cells. Pembrolizumab is an anti-PD1 agent, which has been related to an increased risk of various neurological irAE (n-irAEs). Here, we present a rare case of pembrolizumab-induced neuropathy of cranial nerves. Case Report: A 72-year-old patient was diagnosed with a lung adenocarcinoma in February 2018 (EGFR-, ALK-, and PDL1 90%)...
2021: Frontiers in Neurology
Pritikanta Paul, Rocio Vazquez Do Campo, Teerin Liewluck, Elie Naddaf
Ranolazine is an anti-ischemic drug often used along with statins in patients with ischemic heart disease. Ranolazine-induced proximal myopathy or rhabdomyolysis have been rarely reported, but toxic effects of statins could not be completely ruled out in those cases. We report a 68-year-old man with ranolazine-induced myopathy who presented with respiratory insufficiency and head drop. Creatine kinase level was normal. The Patient continued to worsen despite statin cessation but markedly improved after stopping ranolazine...
March 22, 2021: Neuromuscular Disorders: NMD
Takahiro Ota, Kosuke Yoshida, Yasuhiro Suzuki, Kenji Kuroda, Takashi Kimura
There have been a few reports on Dipeptidyl peptidase (DPP)-4 inhibitor-induced dropped head syndrome. However, there has been no known report on temporal changes in MRI findings. The patient described here was a 63-year-old man who was prescribed oral sitagliptin (50 mg/day) in February 2019. He experienced a dropped head from mid-January 2020, and in early April that year, he was admitted to our hospital for further evaluation. Weakness of the cervical extensor muscles (MMT 3) was noted, and MRI findings showed that the posterior cervical muscle group was hyperintense on short inversion time inversion recovery (STIR)...
April 17, 2021: Rinshō Shinkeigaku, Clinical Neurology
Chang-Ning Fu, Jia-Wen Song, Zhi-Peng Song, Qian-Wen Wang, Wen-Wu Bai, Tao Guo, Peng Li, Chao Liu, Shuang-Xi Wang, Bo Dong
BACKGROUNDS: A major side effect of statin, a widely used drug to treat hyperlipidemia, is skeletal myopathy through cell apoptosis. The aim of this study is to investigate the roles of microRNA in statin-induced injury. METHODS: Apolipoprotein E knockout (ApoE-/-) mice were administered with simvastatin (20 mg/kg/day) for 8 weeks. Exercise capacity was evaluated by hanging grid test, forelimb grip strength, and running tolerance test. RESULTS: In cultured skeletal muscle cells, statin increased the levels of miR-1a but decreased the levels of mitogen-activated protein kinase kinase kinase 1 (MAP3K1) in a time or dose dependent manner...
April 16, 2021: Aging
David Cha, Fan Wang, Basanti Mukerji, Vaskar Mukerji
Statins are among the most frequently prescribed drugs as they effectively lower cardiovascular mortality. Atherosclerotic plaques are stabilized and lipid levels are lowered, as statins inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. Patients placed on these drugs frequently report muscle aches, but true myositis that would call for discontinuance of the drug is actually uncommon. Workup for statin-induced myositis would require ruling out other causes of myositis and muscular dystrophies, and this can often be perplexing for the primary care physician to whom these patients initially present...
March 9, 2021: Curēus
Maryam Nemati, Meena Srai, Rajani Rudrangi
Statins are one of the most widely prescribed drugs in the world. One of the common side effects of statin use is myopathy. We report a case of statin-induced autoimmune myopathy, which is a variant of statin-induced myopathy. A 56-year-old female with a history of hypertension, hyperlipidemia, cerebral aneurysm status post clipping, and seizure disorder presented with progressive muscle weakness. Her initial laboratory results demonstrated an elevated creatine phosphokinase (CPK) of 17,144 IU/L. The patient's atorvastatin was discontinued and she was placed on high-rate intravenous fluids; however, despite this, her CPK remained elevated...
February 26, 2021: Curēus
Claudia Cristina Biguetti, Joel Ferreira Santiago Junior, Matthew William Fiedler, Mauro Toledo Marrelli, Marco Brotto
The aim of this systematic review was to perform qualitative and quantitative analysis on the toxic effects of chloroquine (CQ) and hydroxychloroquine (HCQ) on skeletal muscles. We designed the study according to PRISMA guidelines. Studies for qualitative and quantitative analyses were selected according to the following inclusion criteria: English language; size of sample (> 5 patients), adult (> age of 18) patients, treated with CQ/HCQ for inflammatory diseases, and presenting and not presenting with toxic effects on skeletal muscles...
March 23, 2021: Scientific Reports
Youngsook Choi, Heymin Seo, Mina Cho, Joohee Kim, Hak Suk Chung, Icksoo Lee, Min Jung Kim
Excessive alcohol consumption causes the cellular and tissue damage. The toxic metabolites of ethanol are harmful to multiple organ systems, such as the central nervous system, skeletal muscles, and liver, and cause alcohol-induced diseases like cancer, as well as induce hepatotoxicity, and alcoholic myopathy. Alcohol exposure leads to a surge in hepatic alcohol metabolism and oxygen consumption, a decrease in hepatic ATP, and the rapid accumulation of lipid within hepatocytes. Several pathologies are closely linked to defective mitochondrial dynamics triggered by abnormal mitochondrial function and cellular homeostasis, raising the possibility that novel drugs targeting mitochondrial dynamics may have therapeutic potential in restoring cellular homeostasis in ethanol-induced hepatotoxicity...
February 11, 2021: Animal Cells and Systems
Pobitra Borah, Pran Kishore Deb, Balakumar Chandrasekaran, Manoj Goyal, Monika Bansal, Snawar Hussain, Pottathil Shinu, Katharigatta N Venugopala, Nizar A Al-Shar'i, Satyendra Deka, Vinayak Singh
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to the angiotensin-converting enzyme 2 (ACE2) receptor and invade the human cells to cause COVID-19-related pneumonia. Despite an emphasis on respiratory complications, the evidence of neurological manifestations of SARS-CoV-2 infection is rapidly growing, which is substantially contributing to morbidity and mortality. The neurological disorders associated with COVID-19 may have several pathophysiological underpinnings, which are yet to be explored...
2021: Frontiers in Molecular Biosciences
Giulia Maria Camerino, Nancy Tarantino, Ileana Canfora, Michela De Bellis, Olimpia Musumeci, Sabata Pierno
Statins are the most prescribed and effective drugs to treat cardiovascular diseases (CVD). Nevertheless, these drugs can be responsible for skeletal muscle toxicity which leads to reduced compliance. The discontinuation of therapy increases the incidence of CVD. Thus, it is essential to assess the risk. In fact, many studies have been performed at preclinical and clinical level to investigate pathophysiological mechanisms and clinical implications of statin myotoxicity. Consequently, new toxicological aspects and new biomarkers have arisen...
February 19, 2021: International Journal of Molecular Sciences
Ubaid Tariq, Shravan Kumar Uppulapu, Sanjay K Banerjee
Glycogen synthase kinase 3 (GSK-3) is a ubiquitously expressed serine/threonine kinase and was first identified as a regulator of glycogen synthase enzyme and glucose homeostasis. It regulates cellular processes like cell proliferation, metabolism, apoptosis and development. Recent findings suggest that GSK-3 is required to maintain the normal cardiac homeostasis that regulates cardiac development, proliferation, hypertrophy and fibrosis. GSK-3 is expressed as two isoforms, α and β. Role of GSK-3α and GSK-3β in cardiac biology is well documented...
February 23, 2021: Current Drug Targets
Natalia Alzueta, Marta Marin, Marta Castresana, Ana Gascón, María Pío, María Jesús Iguzquiza
Statins are widely used in the treatment of hypercholesterolemia. Muscle weakness and elevated creatine kinase (CK) are frequent side effects of statins with an incidence of about 15%. Statin-associated myopathy is more common in people who receive multiple drugs, the elderly or women but the mechanism underlying it is still unclear. These symptoms generally improve after drug discontinuation. However, there is a type of autoimmune mediated myopathy characterised by the persistence of muscle weakness and CK elevation after stopping statins...
March 2021: European Journal of Hospital Pharmacy. Science and Practice
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