Drug-induced Myopathies

2021 ◽  
Author(s):  
Jürgen Steinmeyer ◽  
Johannes Flechtenmacher
Keyword(s):  
Kidney Failure ◽  
Clinical Symptoms ◽  
Serum Levels ◽  
Drug Dosage ◽  
Lipid Lowering ◽  
Drug Induced ◽  
Drug Classes ◽  
Alternative Drug ◽  
High Doses ◽  
Toxic Myopathy

AbstractDifferential 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. Some drug interactions, e.g. those that are metabolised via the enzyme CYP3A4, can increase the serum levels of the drugs and drug-induced toxicity. A careful history of patientʼs drug and alcohol consumption is therefore vital. Clinical symptoms depend on the drug, dosage and patientʼs sensitivity. They can vary from asymptomatic increase in serum levels of creatine kinase, mild myalgia and cramps to muscle weakness, rhabdomyolysis, kidney failure and even death. The pathogenesis is often only partially known and multifactorial. Toxic myopathy is often reversible once the drug is discontinued, alternative drug therapy is started or a different dosage regimen is chosen. Complications such as acute kidney failure must be avoided, and analgesic therapy may be indicated.

scholarly journals Toxic myopathies: muscle biopsy features

2007 ◽  
Vol 65 (1) ◽  
pp. 82-86 ◽  
Author(s):  
Rosana Herminia Scola ◽  
Eduardo Rafael Pereira ◽  
Paulo José Lorenzoni ◽  
Lineu César Werneck
Keyword(s):  
Muscle Biopsy ◽  
Serum Levels ◽  
Normal Serum ◽  
Serum Creatine Kinase ◽  
Toxic Substances ◽  
Drug Induced ◽  
Needle Electromyography ◽  
Fiber Atrophy ◽  
Toxic Myopathy

Several drugs and toxic substances can cause muscular abnormalities and are frequent causes of acquired myopathies. We present a series of 32 patients, predominance of young adult patients, diagnosed with toxic myopathy. The most common substances inducing myopathy were corticosteroids (56.2%) followed by the propoxyphene, neuroleptics, zidovudine and drug-induced hypokalemia. The investigation showed normal serum creatine kinase levels in 65.4%, myopathic pattern of the needle electromyography in 40% and the more frequent histological diagnosis of the muscle biopsy was type 2 fiber atrophy (59.3%). Clinical features, etiology, course of the disease, serum levels of muscular enzymes, electromyographic features and, especially, muscle biopsy features are discussed.

scholarly journals Drug-associated thrombocytopenia

Hematology ◽  
2018 ◽  
Vol 2018 (1) ◽  
pp. 576-583 ◽  
Author(s):  
Tamam Bakchoul ◽  
Irene Marini
Keyword(s):  
Platelet Count ◽  
Clinical Symptoms ◽  
Scoring Systems ◽  
Severe Thrombocytopenia ◽  
Thromboembolic Complications ◽  
Drug Induced ◽  
Increased Risk ◽  
High Doses ◽  
Risk Of Hemorrhage

Abstract Many drugs have been implicated in drug-induced immune thrombocytopenia (DITP). Patients with DITP develop a drop in platelet count 5 to 10 days after drug administration with an increased risk of hemorrhage. The diagnosis of DITP is often challenging, because most hospitalized patients are taking multiple medications and have comorbidities that can also cause thrombocytopenia. Specialized laboratory diagnostic tests have been developed and are helpful to confirm the diagnosis. Treatment of DITP involves discontinuation of the offending drug. The platelet count usually starts to recover after 4 or 5 half-lives of the responsible drug or drug metabolite. High doses of intravenous immunoglobulin can be given to patients with severe thrombocytopenia and bleeding. Although in most cases, DITP is associated with bleeding, life-threatening thromboembolic complications are common in patients with heparin-induced thrombocytopenia (HIT). Binding of antiplatelet factor 4/heparin antibodies to Fc receptors on platelets and monocytes causes intravascular cellular activation, leading to an intensely prothrombotic state in HIT. The clinical symptoms include a decrease in platelet counts by >50% and/or new thromboembolic complications. Two approaches can help to confirm or rule out HIT: assessment of the clinical presentation using scoring systems and in vitro demonstration of antiplatelet factor 4/heparin antibodies. The cornerstone of HIT management is immediate discontinuation of heparin when the disease is suspected and anticoagulation using nonheparin anticoagulant. In this review, we will provide an update on the pathophysiology, diagnosis, and management of both DITP and HIT.

A Case Report of Neurotoxicity After Prolonged Doses of Acyclovir in a Patient With Renal Dysfunction

2019 ◽  
Vol 33 (2) ◽  
pp. 217-221 ◽  
Author(s):  
Godsfavour O. Umoru ◽  
Punit J. Shah ◽  
Farheen Tariq
Keyword(s):  
Renal Dysfunction ◽  
Viral Infections ◽  
Clinical Symptoms ◽  
Plasma Concentrations ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Serum Levels ◽  
Drug Induced ◽  
Stage Renal Disease ◽  
End Stage

Renal dysfunction is a significant risk factor for acyclovir-induced neurotoxicity and altered mentation and myoclonic movements are the most common clinical symptoms observed. In majority of reported cases, neurological sequelae associated with acyclovir-induced neurotoxicity often mimic viral infections of the central nervous system and makes diagnosis of the former challenging. Although plasma concentrations of the drug may not always correlate with neurotoxic symptoms, obtaining serum levels of acyclovir may be helpful in confirming drug-induced neurotoxicity. Hemodialysis has been shown to significantly improve altered mentation in patients with suspected or confirmed acyclovir-induced neurotoxicity. Here, we report a definite case of acyclovir-induced neurotoxicity in a patient with end-stage renal disease. Clinical improvements in neurologic symptoms were observed following discontinuation of the drug and hemodialysis.

scholarly journals Development of a PROTAC-Based Targeting Strategy Provides a Mechanistically Unique Mode of Anti-Cytomegalovirus Activity

2021 ◽  
Vol 22 (23) ◽  
pp. 12858
Author(s):  
Friedrich Hahn ◽  
Stuart T. Hamilton ◽  
Christina Wangen ◽  
Markus Wild ◽  
Jintawee Kicuntod ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Clinical Symptoms ◽  
Adenovirus Type ◽  
Drug Induced ◽  
Varicella Zoster ◽  
Bifunctional Molecules ◽  
Medical Needs ◽  
Drug Classes ◽  
Spectrum Activity ◽  
Target Binding

Human cytomegalovirus (HCMV) is a major pathogenic herpesvirus that is prevalent worldwide and it is associated with a variety of clinical symptoms. Current antiviral therapy options do not fully satisfy the medical needs; thus, improved drug classes and drug-targeting strategies are required. In particular, host-directed antivirals, including pharmaceutical kinase inhibitors, might help improve the drug qualities. Here, we focused on utilizing PROteolysis TArgeting Chimeras (PROTACs), i.e., hetero-bifunctional molecules containing two elements, namely a target-binding molecule and a proteolysis-inducing element. Specifically, a PROTAC that was based on a cyclin-dependent kinase (CDK) inhibitor, i.e., CDK9-directed PROTAC THAL-SNS032, was analyzed and proved to possess strong anti-HCMV AD169-GFP activity, with values of EC50 of 0.030 µM and CC50 of 0.175 µM (SI of 5.8). Comparing the effect of THAL-SNS032 with its non-PROTAC counterpart SNS032, data indicated a 3.7-fold stronger anti-HCMV efficacy. This antiviral activity, as illustrated for further clinically relevant strains of human and murine CMVs, coincided with the mid-nanomolar concentration range necessary for a drug-induced degradation of the primary (CDK9) and secondary targets (CDK1, CDK2, CDK7). In addition, further antiviral activities were demonstrated, such as the inhibition of SARS-CoV-2 replication, whereas other investigated human viruses (i.e., varicella zoster virus, adenovirus type 2, and Zika virus) were found insensitive. Combined, the antiviral quality of this approach is seen in its (i) mechanistic uniqueness; (ii) future options of combinatorial drug treatment; (iii) potential broad-spectrum activity; and (iv) applicability in clinically relevant antiviral models. These novel data are discussed in light of the current achievements of anti-HCMV drug development.

The Effect of Immunosuppression on Selected Antioxidant Parameters in Patients with Graves’ Disease with Active Thyroid-Associated Orbitopathy

2020 ◽  
Author(s):  
Magdalena Londzin-Olesik ◽  
Beata Kos-Kudla ◽  
Jacek Karpe ◽  
Aleksandra Nowak ◽  
Mariusz Nowak
Keyword(s):  
Oxidative Stress ◽  
Clinical Symptoms ◽  
Immunosuppressive Treatment ◽  
Serum Vitamin ◽  
Serum Levels ◽  
Paraoxonase 1 ◽  
Control Group ◽  
Graves Disease ◽  
Methylprednisolone Treatment ◽  
Antioxidant Parameters

Abstract Background and Study Aims Thyroid-associated orbitopathy, the most common extrathyroidal manifestation of Graves’ disease, is an autoimmune inflammation of orbital soft tissue. We report the study assessing the effect of immunosuppressive treatment with methylprednisolone on selected antioxidant parameters in patients with Graves’ disease with active thyroid-associated orbitopathy. Patients and Methods Activity and serum levels of selected antioxidant parameters as well as lipid peroxidation products were determined in a group of 56 patients with active thyroid-associated orbitopathy at three time-points: at baseline, after the discontinuation of intravenous methylprednisolone treatment and at 3 months after the discontinuation of additional oral methylprednisolone treatment. A control group consisted of 20 healthy age- and sex-matched volunteers. Results We found an increased activity of superoxide dismutase and glutathione peroxidase and increased serum levels of uric acid, malondialdehyde and conjugated dienes, as well as a reduced activity of paraoxonase-1 and reduced serum vitamin C level in the study group at baseline. Systemic intravenous and oral methylprednisolone therapy led to normalization of activity and concentration of the most studied parameters. Conclusion Results of our study confirmed that oxidative stress is one of the factors involved in the pathogenesis of thyroid-associated orbitopathy and the methyloprednisolone treatment is effective in reducing both clinical symptoms and oxidative stress in patients with this disease.

scholarly journals Longitudinal assessment of S100B serum levels and clinical factors in youth patients with mood disorders

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Aleksandra Rajewska-Rager ◽  
Monika Dmitrzak-Weglarz ◽  
Pawel Kapelski ◽  
Natalia Lepczynska ◽  
Joanna Pawlak ◽  
...  
Keyword(s):  
Mood Disorders ◽  
Calcium Binding ◽  
Clinical Symptoms ◽  
Small Sample Size ◽  
Serum Levels ◽  
Small Sample ◽  
Drop Out ◽  
Control Group ◽  
Longitudinal Assessment ◽  
Depressed Group

AbstractMood disorders have been discussed as being in relation to glial pathology. S100B is a calcium-binding protein, and a marker of glial dysfunctions. Although alterations in the S100B expression may play a role in various central nervous system diseases, there are no studies on the potential role of S100B in mood disorders in adolescents and young adults . In a prospective two-year follow-up study, peripheral levels of S100B were investigated in 79 adolescent/young adult patients (aged 14–24 years), diagnosed with mood disorders and compared with 31 healthy control subjects. A comprehensive clinical interview was conducted which focused on clinical symptoms and diagnosis change. The diagnosis was established and verified at each control visit. Serum S100B concentrations were determined. We detected: lower S100B levels in medicated patients, compared with those who were drug-free, and healthy controls; higher S100B levels in a depressed group with a family history of affective disorder; correlations between age and medication status; sex-dependent differences in S100B levels; and lack a of correlation between the severity of depressive or hypo/manic symptoms. The results of our study indicate that S100B might be a trait-dependent rather than a state-dependent marker. Due to the lack of such studies in the youth population, further research should be performed. A relatively small sample size, a lack of exact age-matched control group, a high drop-out rate.

scholarly journals Age- and Gender-Related Differences in LDL-Cholesterol Management in Outpatients with Type 2 Diabetes Mellitus

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Giuseppina Russo ◽  
Basilio Pintaudi ◽  
Carlo Giorda ◽  
Giuseppe Lucisano ◽  
Antonio Nicolucci ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Serum Levels ◽  
Diabetes Duration ◽  
Lipid Lowering ◽  
Age And Gender ◽  
Chd Risk ◽  
And Gender

Background. Dyslipidemia contribute to the excess of coronary heart disease (CHD) risk observed in women with type 2 diabetes (T2DM). Low density lipoprotein-cholesterol (LDL-C) is the major target for CHD prevention, and T2DM women seem to reach LDL-C targets less frequently than men.Aim. To explore age- and gender-related differences in LDL-C management in a large sample of outpatients with T2DM.Results. Overall, 415.294 patients (45.3% women) from 236 diabetes centers in Italy were included. Women were older and more obese, with longer diabetes duration, higher total-cholesterol, LDL-C, and HDL-C serum levels compared to men (P<0.0001). Lipid profile was monitored in ~75% of subjects, women being monitored less frequently than men, irrespective of age. More women did not reach the LDL-C target as compared to men, particularly in the subgroup treated with lipid-lowering medications. The between-genders gap in reaching LDL-C targets increased with age and diabetes duration, favouring men in all groups.Conclusions. LDL-C management is worst in women with T2DM, who are monitored and reach targets less frequently than T2DM men. Similarly to men, they do not receive medications despite high LDL-C. These gender discrepancies increase with age and diabetes duration, exposing older women to higher CHD risk.

scholarly journals Drug-Induced Photosensitivity—From Light and Chemistry to Biological Reactions and Clinical Symptoms

2021 ◽  
Vol 14 (8) ◽  
pp. 723
Author(s):  
Justyna Kowalska ◽  
Jakub Rok ◽  
Zuzanna Rzepka ◽  
Dorota Wrześniok
Keyword(s):  
Defense Mechanisms ◽  
Clinical Symptoms ◽  
Chemical Properties ◽  
Additional Treatment ◽  
Cosmetic Products ◽  
Aesthetic Value ◽  
Drug Usage ◽  
Drug Induced ◽  
Biochemical Level ◽  
The Aesthetic

Photosensitivity is one of the most common cutaneous adverse drug reactions. There are two types of drug-induced photosensitivity: photoallergy and phototoxicity. Currently, the number of photosensitization cases is constantly increasing due to excessive exposure to sunlight, the aesthetic value of a tan, and the increasing number of photosensitizing substances in food, dietary supplements, and pharmaceutical and cosmetic products. The risk of photosensitivity reactions relates to several hundred externally and systemically administered drugs, including nonsteroidal anti-inflammatory, cardiovascular, psychotropic, antimicrobial, antihyperlipidemic, and antineoplastic drugs. Photosensitivity reactions often lead to hospitalization, additional treatment, medical management, decrease in patient’s comfort, and the limitations of drug usage. Mechanisms of drug-induced photosensitivity are complex and are observed at a cellular, molecular, and biochemical level. Photoexcitation and photoconversion of drugs trigger multidirectional biological reactions, including oxidative stress, inflammation, and changes in melanin synthesis. These effects contribute to the appearance of the following symptoms: erythema, swelling, blisters, exudation, peeling, burning, itching, and hyperpigmentation of the skin. This article reviews in detail the chemical and biological basis of drug-induced photosensitivity. The following factors are considered: the chemical properties, the influence of individual ranges of sunlight, the presence of melanin biopolymers, and the defense mechanisms of particular types of tested cells.

A case of statin-induced liver injury with positive rechallenge with a second statin. Is there a class effect?

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Giovanna Onfiani ◽  
Fabio Nascimbeni ◽  
Francesca Carubbi
Keyword(s):  
Liver Injury ◽  
Clinical Symptoms ◽  
High Risk Population ◽  
Drug Induced ◽  
Case Presentation ◽  
Drug Induced Liver Injury ◽  
Aged Woman ◽  
Cardiovascular Morbidity And Mortality ◽  
Middle Aged Woman

Abstract Objectives Statins have proved to reduce cardiovascular morbidity and mortality in high-risk population and are generally well tolerated, although adverse events can occur. Up to 3% of patients develop aminotransferases elevation, which usually normalizes with continued treatment and hardly is associated with clinical symptoms. Serious statin-related liver injury is exceedingly rare. Furthermore, literature regarding rechallenge with a second statin is extremely poor. Some authors caution that re-exposure to these drugs is associated with a more serious liver injury but safe switching to a second statin after drug-induced liver injury (DILI) is also reported. Case presentation We describe a case of a middle-aged woman who developed hepatocellular liver injury after simvastatin dose escalation; a rechallenge with low dose rosuvastatin caused rapid recurrence of DILI. Conclusions In our opinion, clinicians should be very cautious upon rechallenge and closely follow-up patients who experienced statin-induced liver injury when trying re-exposure to another statin.

Drug-Induced Restless Legs Syndrome

2018 ◽  
Vol 52 (7) ◽  
pp. 662-672 ◽  
Author(s):  
Edna Patatanian ◽  
Melanie K. Claborn
Keyword(s):  
Restless Legs Syndrome ◽  
English Language ◽  
Case Reports ◽  
Data Extraction ◽  
Case Series ◽  
Predisposing Factors ◽  
Drug Induced ◽  
Restless Legs ◽  
Drug Classes ◽  
Study Selection

Objective: To review the literature on drug-induced restless legs syndrome (DI-RLS). Data Sources: The review included a search for English-language literature from 1966 to December 2017 in the MEDLINE, PubMed, and Ovid databases using the following search terms: restless legs syndrome (RLS), periodic limb movement, adverse effects, and drug-induced. In addition, background articles on the pathophysiology, etiology, and epidemiology of RLS were retrieved. Bibliographies of relevant articles were reviewed for additional citations. Study Selection and Data Extraction: All case reports, case series, and review articles of DI-RLS were identified and analyzed. There were only a small number of controlled clinical trials, and most data were from case reports and case series. Results: Several drugs and drug classes have been implicated in DI-RLS, with antidepressants, antipsychotics, and antiepileptics having the most evidence. In addition, RLS may be linked with a number of disorders or underlying predisposing factors as well. Conclusions: The prevalence of RLS is variable and ranges from 3% to 19% in the general population. There are many predisposing factors to RLS, but an emerging body of evidence suggests that there is an association between numerous drugs and RLS.

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