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Drug induced musculoskeletal disorders can potentially affect the spectrum of anatomical structures including bone, connective tissue and the musculature. Skeletal muscles represent a significant proportion of the body’s mass, receive a large fraction of blood supply, and are metabolically highly active. This tissue therefore has significant exposu...
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Rhabdomyolysis is the combination of symptoms (myalgia, weakness and muscle swelling) and a substantial rise in serum creatine kinase (CK) >50 000 IU/L; there are many causes, but here we specifically address exertional rhabdomyolysis. The consequences of this condition can be severe, including acute kidney injury and requirement for higher level c...
Citations
... High-intensity statins (e.g. atorvastatin and rosuvastatin) are more likely to induce myopathic symptoms compared to moderate-intensity statins [7]. High-intensity statins are lipophilic and predominantly metabolized by the CYP3A4 system [7]. ...
... atorvastatin and rosuvastatin) are more likely to induce myopathic symptoms compared to moderate-intensity statins [7]. High-intensity statins are lipophilic and predominantly metabolized by the CYP3A4 system [7]. Concomitant CYP inhibitor use increases the serum concentration of CYP substrates, potentiating their toxic effects. ...
Statins constitute a cornerstone in the primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD). The routine use of these lipid-lowering agents may lead to unintentional neglect of their well-known myotoxic properties. We report the case of a 77-year-old female with a two-year history of rosuvastatin use who presented with progressive bilateral upper and lower extremity muscular weakness for one week, which improved upon discontinuation of her long-term statin therapy. The authors aim to draw attention to this potentially underdiagnosed cause of disability. It is imperative that clinicians are able to appreciate the myopathic spectrum of statin therapy, irrespective of the duration of use. Myonecrosis, in particular, can progress to rhabdomyolysis, leading to irreversible renal dysfunction, electrolyte abnormalities, and subsequent cardiac dysrhythmias. Ultimately, statin-induced myopathy may significantly hinder activities of daily living and impair quality of life. It is, however, a reversible condition if diagnosed and appropriately managed early on. Clinicians are encouraged to acquaint themselves with the symptomatology and relevant laboratory values that commonly accompany this acute condition.
... Skeletal muscle constitutes a significant proportion of our body mass and relies on thyroid hormone for optimum development, function, and regeneration (1,2,3,4,5). Thyroid dysregulation, unsurprisingly, can lead to myopathic symptoms and altered basal muscle metabolism (1,2,3,4,5,6). ...
... Skeletal muscle constitutes a significant proportion of our body mass and relies on thyroid hormone for optimum development, function, and regeneration (1,2,3,4,5). Thyroid dysregulation, unsurprisingly, can lead to myopathic symptoms and altered basal muscle metabolism (1,2,3,4,5,6). While musculoskeletal complaints are common in thyroid disorders, skeletal muscle is also vulnerable to the circulating ATD used to combat these disorders (1,2,4). ...
... Thyroid dysregulation, unsurprisingly, can lead to myopathic symptoms and altered basal muscle metabolism (1,2,3,4,5,6). While musculoskeletal complaints are common in thyroid disorders, skeletal muscle is also vulnerable to the circulating ATD used to combat these disorders (1,2,4). Cases of ATD-induced myopathy, characterized by proximal muscle weakness (without other cause for myopathy), elevated creatinine kinase, a temporal relationship between the commencement of treatment and symptomatology, and the resolution of symptoms upon withdrawal of the medication have been reported (1,2,3,4). ...
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.
Learning points:
Musculoskeletal complaints can relate to unidentified and untreated hyperthyroidism. However one must be mindful that the treatment for these disorders can too induce myopathies. ATD-induced myopathy should be considered when there is a temporal relationship between introduction of ATDs and the onset of symptoms. If ATD-induced myopathy is being considered, other causes of myopathy should still be outruled. Prompt discontinuation of potentially offending medications may provide resolution of symptoms and avoid significant consequences.
... Среди факторов риска СПМ-СПС упоминается гипотиреоз, но данные о его роли неоднозначны: в большинстве работ изучали недиагностированный гипотиреоз [4][5][6], вопрос же о безопасности статинов при компенсированной тиреоидной недостаточности остается открытым. ...
Background:
There is no unequivocal opinion regarding the safety of statin in patients with hypothyroidism. However, based on some new data, it can be assumed that hypothyroidism, even in a stage of compensation, may cause muscle damage in patients receiving statins. As part of this study, this hypothesis was tested, and was confirmed.
Aims:
To study the possibility of muscle damage and the nature of muscle metabolism in patients with compensated hypothyroidism who takes statin.
Materials and methods:
The study is transverse and observational with the inclusion of 120 women, subdivided on three groups (n=40). The main group of patients with hypothyroidism who took statins (group 1) was compared with two control groups, including those who took statins without hypothyroidism (group 2), and who did not take statins with hypothyroidism (group 3).
Results:
Patients taking statins and have compensated hypothyroidism are more likely to develop complaints of muscle pain, which are often associated with the elevation of muscle lesion markers, as well as the presence of the C allele in the SLCO1B1*5 gene (c.521T>C). In patients with compensated hypothyroidism, relative frequency of occurance of muscle pain syndrome associated with CPK elevation increases with TSH levels above 2.86 mU/L. Compensated hypothyroidism increases the possibility of development of SPM-ATP by 2.7 times.
Conclusions:
Compensated hypothyroidism is not a contraindication for statin therapy. However, the presence of even compensated hypothyroidism in patients taking statins increases the possibility of the development of muscle symptoms associated with taking statins, and requires additional monitoring of the clinical and biochemical parameters of muscle metabolism (especially the level of CPK).
... Prednisone usage was significantly associated with an increased odds ratio for exhibiting many abnormal phenotypes that are consistent with the known effects of prednisone (Table 2), such as hypoalbuminemia (HP:0003073), 16 neutrophilia (HP:0011897), 17 monocytosis (HP:0012311), 18 leukocytosis (HP:0001974), 18 hypokalemia (HP:0002900), 19 and elevated serum creatine phosphokinase (HP:0003236). 20 An acute asthma diagnosis was significantly associated with seven phenotypes, abnormal metabolism (HP:0032245), abnormality of vitamin metabolism (HP:0100508), increased red blood cell count (HP:0020059), increased VLDL cholesterol concentration (HP:0003362), and eosinophilia (HP:0001880), and two ancestor terms of eosinophilia, abnormal eosinophil count (HP:0020064), and abnormal eosinophil morphology (HP:0001879). Eosinophilia is a well-established marker for acute allergic asthma. ...
Electronic Health Record (EHR) systems typically define laboratory test results using the Laboratory Observation Identifier Names and Codes (LOINC) and can transmit them using Fast Healthcare Interoperability Resource (FHIR) standards. LOINC has not yet been semantically integrated with computational resources for phenotype analysis. Here, we provide a method for mapping LOINC-encoded laboratory test results transmitted in FHIR standards to Human Phenotype Ontology (HPO) terms. We annotated the medical implications of 2923 commonly used laboratory tests with HPO terms. Using these annotations, our software assesses laboratory test results and converts each result into an HPO term. We validated our approach with EHR data from 15,681 patients with respiratory complaints and identified known biomarkers for asthma. Finally, we provide a freely available SMART on FHIR application that can be used within EHR systems. Our approach allows readily available laboratory tests in EHR to be reused for deep phenotyping and exploits the hierarchical structure of HPO to integrate distinct tests that have comparable medical interpretations for association studies.
... Using logistic regression, we assessed the contribution of frequent prednisone prescription and the presence of acute asthma diagnosis to each phenotypic abnormality. Prednisone usage was significantly associated with an increased odds ratio for exhibiting many abnormal phenotypes that are consistent with the known effects of prednisone (Table 2), such as Hypoalbuminemia (HP:0003073) 15 , Neutrophilia (HP:0011897) 16 , Monocytosis (HP:0012311) 17 , Leukocytosis (HP:0001974) 17 , Hypokalemia (HP:0002900) 18 , and Elevated serum creatine phosphokinase (HP:0003236) 19 . An acute asthma diagnosis was significantly associated with five phenotypes, Increased red blood cell count (HP:0020059), Increased VLDL cholesterol concentration (HP:0003362) and Eosinophilia (HP:0001880), and two ancestor terms of Eosinophilia, Abnormal eosinophil count (HP:0020064) and Abnormal eosinophil morphology (HP:0001879). ...
Electronic Health Record (EHR) systems typically define laboratory test results using the Laboratory Observation Identifier Names and Codes (LOINC) and can transmit them using Fast Healthcare Interoperability Resource (FHIR) standards. LOINC has not yet been semantically integrated with computational resources for phenotype analysis. Here, we provide a method for mapping LOINC-encoded laboratory test results transmitted in FHIR standards to the Human Phenotype Ontology (HPO) terms. We annotated the medical implications of 2421 commonly used laboratory tests with HPO terms. Using these annotations, a software assesses laboratory test results and converts each into an HPO term. We validated our approach with EHR data from 15,681 patients with respiratory complaints and identified known biomarkers for asthma. Finally, we provide a freely available SMART on FHIR application that can be used within EHR systems. Our approach allows reusing readily available laboratory tests in EHR for deep phenotyping and using the hierarchical structure of HPO for association studies with medical outcomes and genomics.
One Sentence Summary
We present an approach to semantically integrating LOINC-encoded laboratory data with the Human Phenotype Ontology and show that the integrated LOINC data can be used to identify biomarkers for asthma from electronic health record data.
... Однако статины не свободны от побочных эффектов, в том числе в отношении мышечной системы. Среди факторов риска статин-индуцированной миопатии (СИМ) называют высокие дозы статинов [2,3], наличие полиморфизма гена SLCO1B1*5 (c.521T>C) [4], а также гипотиреоз [1,5]. ...
Aim: to assess the influence of compensated hypothyroidism and SLCO1B1 *5 (c.521T>C) gene polymorphism on the clinical and laboratory signs of the muscle damage during statin therapy.
Methods: assessment of symptoms and markers of the muscle damage and SLCO1B1 *5 (c.521T>C) genotyping were performed in 33 patients with primary hypothyroidism taking statins, in 31 patients taking statins without hypothyroidism and in 33 patients with primary hypothyroidism without statins taking.
Results: muscle pain was observed more often in the group of the patients with compensated hypothyroidism on the background of statins taking compared with other groups (45,5, 16,1 and 30,3 %, respectively, p=0,048). Only in this group the pain was associated with increased levels of creatine- kinase (171,0±108,12 and 110,0±43,81U/L, in the presence and absence of the pain, p=0,049), LDH (369,5±66,22 and 305,6±41,98 U/L, р=0,007), myoglobin titer (90,7±109,89 and 41,1±28,56, р=0,005), and more frequent occurrence of TC and CC genotypes of SLCO1B1*5 (c.521T>C) (68,4 и 28,6%, р=0,0027).
Conclusions: the patients with compensated hypothyroidism have a higher risk of statin-induced myopathy increasing if the TC heterozygotes or CC homozygotes of SLCO1B1 *5 (c.521T>C) gene are present, which requires thorough monitoring of clinical and biochemical muscle damage signs in case of its detection.
... Samples were collected from the venous blood (2 ml from each participant) after 3 hours of oral administration, however subjects with recent seizure episodes were excluded from the study because of elevated CK which may last 3 to 8 days (19) number of seizure episodes were tracked by interviewing the guardians of children and adverse effects are monitored by examining present and past medication charts of the patients. Subjects with conditions like hypothyroidism, hyperthyroidism, who underwent resent surgery or trauma, patients on other myopathy inducing drug (except study drugs), hepatic or renal disease, (20) patients who are newly prescribed on sodium valproate were also excluded. Samples were collected in to Eppendorf tubes which are centrifuged at 4,000 rpm and stored at -20°C to measure free fraction of VPA. 1 ml of the blood sample was collected in to amicon tubes and centrifuged at 4,000 rpm for protein separation and obtained clear liquid is stored at -20°C. ...
Objectives. To measure and compare free fraction of serum levels of VPA (valproic acid) between non-malnourished and malnourished epileptic children and to evaluate the adverse effects (myopathy, hepatotoxicity). Material and methods. It is a prospective comparative observational case control study in which forty epileptic children (malnourished: 18 male/8 female, age 8.3±2.5, non-malnourished: 8 male/6 female, age 8.1±2.1) who fulfilled the inclusion criteria were recruited as study group and twenty children as control group (12male/8 female, age 6.0±2.8). Outcome measures monitored are serum VPA levels (total and free fraction of serum VPA), serum CK (creatinine kinase), SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic-transaminase). Using screening tool for the assessment of malnutrition in pediatrics (STAMP©), subjects are categorized into mild, moderate, severe malnourished as -1SD, -2SD, -3SD respectively Outcomes. There is an elevation in mean free fraction of VPA is 17.3±6.4 μg/ml whereas in non-malnourished group it was found to be 8.7±4.2 μg/ml with P= <0.001. While mean total drug concentration in malnourished and non-malnourished was found to be 88.6±49.9 μg/ml, 70.8±33.9 μg/ml respectively. Mean CK, SGOT, SGPT in control is 29.3±9.9IU/L, 28.5±5.4 IU/L,24.5±4.2 IU/L respectively. whereas mean CK, SGOT, SGPT in malnourished subjects is 16.9±9.1 IU/L, 28.8±8.5 IU/L,25.9±9.1 IU/L Correspondingly .while Mean CK, SGOT, SGPT in non-malnourished individuals is 15.7±11.3 IU/L,32.4±8.8 IU/L, 28.7±7.8 IU/L respectively. No correlation was observed between elevated serum drug concentrations, clinical response and side effects. Conclusion. We observed that clinical response and side effects are serum concentration independent hence our research make unnecessary to monitor serum drug concentration for every individual and drug monitoring should be restricted to subjects with severe ADR’s. Our data also suggest Valproate unveiled mitochondrial myopathy is limited to subgroup of population.
Pain may be a consequence of the medication you are taking. In practice, it is not uncommon for analgesics to induce pain, and one of the most frequently found mechanisms is drug interactions, including the summation of side effects. Unfortunately, drug-induced side effects are still a risk factor for inducing the prescription cascade, which in practice means an increased risk of further complications. The paper describes a case of myalgia as an undesirable effect of the combination of celecoxib with other drugs used in polypharmacy. The paper describes a case of myalgia as an undesirable effect of the combination of celecoxib with other drugs used in polypharmacy.
