Muscle Toxicity of Drugs: When Drugs Turn Physiology into Pathophysiology

2020 ◽  
Vol 100 (2) ◽  
pp. 633-672 ◽  
Author(s):  
Lando Janssen ◽  
Neeltje A. E. Allard ◽  
Christiaan G. J. Saris ◽  
Jaap Keijer ◽  
Maria T. E. Hopman ◽  
...  
Keyword(s):  
High Risk ◽  
Main Part ◽  
Drug Class ◽  
Clinical Manifestations ◽  
Specific Drug ◽  
Drug Induced ◽  
Diagnostic Aid ◽  
Pathological Mechanism ◽  
Toxicity Of Drugs ◽  
Muscle Toxicity

Drugs are prescribed to manage or prevent symptoms and diseases, but may sometimes cause unexpected toxicity to muscles. The symptomatology and clinical manifestations of the myotoxic reaction can vary significantly between drugs and between patients on the same drug. This poses a challenge on how to recognize and prevent the occurrence of drug-induced muscle toxicity. The key to appropriate management of myotoxicity is prompt recognition that symptoms of patients may be drug related and to be aware that inter-individual differences in susceptibility to drug-induced toxicity exist. The most prevalent and well-documented drug class with unintended myotoxicity are the statins, but even today new classes of drugs with unintended myotoxicity are being discovered. This review will start off by explaining the principles of drug-induced myotoxicity and the different terminologies used to distinguish between grades of toxicity. The main part of the review will focus on the most important pathogenic mechanisms by which drugs can cause muscle toxicity, which will be exemplified by drugs with high risk of muscle toxicity. This will be done by providing information on key clinical and laboratory aspects, muscle electromyography patterns and biopsy results, and pathological mechanism and management for a specific drug from each pathogenic classification. In addition, rather new classes of drugs with unintended myotoxicity will be highlighted. Furthermore, we will explain why it is so difficult to diagnose drug-induced myotoxicity, and which tests can be used as a diagnostic aid. Lastly, a brief description will be given of how to manage and treat drug-induced myotoxicity.

scholarly journals 2021 Update on the Clinical Management and Diagnosis of Kawasaki Disease

2021 ◽  
Vol 23 (3) ◽  
Author(s):  
Frank Zhu ◽  
Jocelyn Y. Ang
Keyword(s):  
High Risk ◽  
Kawasaki Disease ◽  
Corticosteroid Therapy ◽  
Clinical Management ◽  
Treatment Guidelines ◽  
Day Treatment ◽  
Significant Proportion ◽  
Clinical Manifestations ◽  
Heart Association ◽  
Ivig Resistance

Abstract Purpose of Review Provide an updated review of the clinical management and diagnosis of Kawasaki disease with inclusion of potential diagnostic difficulties with multisystem inflammatory syndrome in children (MIS-C) given the ongoing COVID-19 pandemic. Recent Findings Adjunctive corticosteroid therapy has been shown to reduce the rate of coronary artery dilation in children at high risk for IVIG resistance in multiple Japanese clinical studies (most notably RAISE study group). Additional adjunctive therapies (etanercept, infliximab, cyclosporin) may also provide limited benefit, but data is limited to single studies and subgroups of patients with cardiac abnormalities. The efficacy of other agents (atorvastatin, doxycycline) is currently being investigated. MIS-C is a clinically distinct entity from KD with broad clinical manifestations and multiorgan involvement (cardiac, GI, hematologic, dermatologic, respiratory, renal). MIS-C with Kawasaki manifestations is more commonly seen in children < 5 years of age. Summary The 2017 American Heart Association (AHA) treatment guidelines have included changes in aspirin dosing (including both 80–100 mg/kg/day and 30–50 mg/kg/day treatment options), consideration of the use of adjuvant corticosteroid therapy in patients at high risk of IVIG resistance, and the change in steroid regimen for refractory KD to include both pulse-dose IVMP and longer course of prednisolone with an oral taper. A significant proportion of children diagnosed with MIS-C, a post-infectious syndrome of SARS-CoV-2 infection, meet criteria for Kawasaki disease. Further investigation is warranted to further delineate these conditions and optimize treatment of these conditions given the ongoing COVID-19 pandemic.

scholarly journals Beta-Lactams Toxicity in the Intensive Care Unit: An Underestimated Collateral Damage?

2021 ◽  
Vol 9 (7) ◽  
pp. 1505
Author(s):  
Claire Roger ◽  
Benjamin Louart
Keyword(s):  
Risk Factors ◽  
Intensive Care Unit ◽  
Intensive Care ◽  
Clinical Manifestations ◽  
Acute Interstitial Nephritis ◽  
Convulsive Status Epilepticus ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Drug Induced ◽  
Icu Patients

Beta-lactams are the most commonly prescribed antimicrobials in intensive care unit (ICU) settings and remain one of the safest antimicrobials prescribed. However, the misdiagnosis of beta-lactam-related adverse events may alter ICU patient management and impact clinical outcomes. To describe the clinical manifestations, risk factors and beta-lactam-induced neurological and renal adverse effects in the ICU setting, we performed a comprehensive literature review via an electronic search on PubMed up to April 2021 to provide updated clinical data. Beta-lactam neurotoxicity occurs in 10–15% of ICU patients and may be responsible for a large panel of clinical manifestations, ranging from confusion, encephalopathy and hallucinations to myoclonus, convulsions and non-convulsive status epilepticus. Renal impairment, underlying brain abnormalities and advanced age have been recognized as the main risk factors for neurotoxicity. In ICU patients, trough concentrations above 22 mg/L for cefepime, 64 mg/L for meropenem, 125 mg/L for flucloxacillin and 360 mg/L for piperacillin (used without tazobactam) are associated with neurotoxicity in 50% of patients. Even though renal complications (especially severe complications, such as acute interstitial nephritis, renal damage associated with drug induced hemolytic anemia and renal obstruction by crystallization) remain rare, there is compelling evidence of increased nephrotoxicity using well-known nephrotoxic drugs such as vancomycin combined with beta-lactams. Treatment mainly relies on the discontinuation of the offending drug but in the near future, antimicrobial optimal dosing regimens should be defined, not only based on pharmacokinetics/pharmacodynamic (PK/PD) targets associated with clinical and microbiological efficacy, but also on PK/toxicodynamic targets. The use of dosing software may help to achieve these goals.

Carnitine Deficiency in Epilepsy: Risk Factors and Treatment

1995 ◽  
Vol 10 (2_suppl) ◽  
pp. 2S32-2S39 ◽  
Author(s):  
David L. Coulter
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Preliminary Data ◽  
Metabolic Diseases ◽  
Drug Effects ◽  
Carnitine Deficiency ◽  
Free Carnitine ◽  
Specific Drug ◽  
Asymptomatic Patients ◽  
The Relationship

Numerous studies have shown that plasma carnitine levels are significantly lower in patients taking valproate than in controls. Free carnitine deficiency is not uncommon in these patients and also occurs in newborns with seizures and in patients taking other anticonvulsant drugs. Carnitine deficiency in epilepsy results from a variety of etiologic factors including underlying metabolic diseases, nutritional inadequacy, and specific drug effects. The relationship between carnitine deficiency and valproate-induced hepatotoxicity is unclear. Carnitine treatment does not always prevent the emergence of serious hepatotoxicity, but it does alleviate valproate-induced hyperammonemia. These studies suggest that specific risk factors for carnitine deficiency can be identified. Preliminary data suggest that carnitine treatment may benefit high-risk, symptomatic patients and those with free carnitine deficiency. Carnitine treatment is not likely to benefit low-risk, asymptomatic patients and those with normal carnitine levels. (J Child Neurol 1995;10(Suppl):2S32-2S39).

scholarly journals Dissecting autism and schizophrenia through neuroimaging genomics

Brain ◽  
2021 ◽  
Author(s):  
Clara A Moreau ◽  
Armin Raznahan ◽  
Pierre Bellec ◽  
Mallar Chakravarty ◽  
Paul M Thompson ◽  
...  
Keyword(s):  
High Risk ◽  
Psychiatric Symptoms ◽  
Clinical Manifestations ◽  
Autism Spectrum ◽  
Case Control ◽  
Effect Sizes ◽  
Case Control Studies ◽  
Top Down ◽  
Bottom Up ◽  
Genomic Variants

Abstract Neuroimaging genomic studies of autism spectrum disorder and schizophrenia have mainly adopted a ‘top-down’ approach, starting with the behavioural diagnosis, and moving down to intermediate brain phenotypes and underlying genetic factors. Advances in imaging and genomics have been successfully applied to increasingly large case-control studies. As opposed to diagnostic-first approaches, the bottom-up strategy starts at the level of molecular factors enabling the study of mechanisms related to biological risk, irrespective of diagnoses or clinical manifestations. The latter strategy has emerged from questions raised by top-down studies: Why are mutations and brain phenotypes over-represented in individuals with a psychiatric diagnosis? Are they related to core symptoms of the disease or to comorbidities? Why are mutations and brain phenotypes associated with several psychiatric diagnoses? Do they impact a single dimension contributing to all diagnoses? In the review, we aimed at summarizing imaging genomic findings in autism and schizophrenia as well as neuropsychiatric variants associated with these conditions. Top-down studies of autism and schizophrenia identified patterns of neuroimaging alterations with small effect-sizes and an extreme polygenic architecture. Genomic variants and neuroimaging patterns are shared across diagnostic categories suggesting pleiotropic mechanisms at the molecular and brain network levels. Although the field is gaining traction; characterizing increasingly reproducible results, it is unlikely that top-down approaches alone will be able to disentangle mechanisms involved in autism or schizophrenia. In stark contrast with top-down approaches, bottom-up studies showed that the effect-sizes of high-risk neuropsychiatric mutations are equally large for neuroimaging and behavioural traits. Low specificity has been perplexing with studies showing that broad classes of genomic variants affect a similar range of behavioral and cognitive dimensions, which may be consistent with the highly polygenic architecture of psychiatric conditions. The surprisingly discordant effect sizes observed between genetic and diagnostic first approaches underscore the necessity to decompose the heterogeneity hindering case-control studies in idiopathic conditions. We propose a systematic investigation across a broad spectrum of neuropsychiatric variants to identify putative latent dimensions underlying idiopathic conditions. Gene expression data on temporal, spatial and cell type organization in the brain have also considerable potential for parsing the mechanisms contributing to these dimensions phenotypes. While large neuroimaging genomic datasets are now available in unselected populations, there is an urgent need for data on individuals with a range of psychiatric symptoms and high-risk genomic variants. Such efforts together with more standardized methods will improve mechanistically informed predictive modeling for diagnosis and clinical outcomes.

Preeclampsia Part 2: fisiopatologia e trattamento

2019 ◽  
Vol 31 (2) ◽  
pp. 79-88
Author(s):  
Stefano Michelassi
Keyword(s):  
High Risk ◽  
Endothelial Dysfunction ◽  
Preterm Delivery ◽  
Systemic Inflammation ◽  
Systemic Disease ◽  
Clinical Manifestations ◽  
Morbidity And Mortality ◽  
Curative Treatment ◽  
Maternal Risks ◽  
New Onset

Preeclampsia is a pregnancy-specific disorder usually defined as new-onset hypertension and proteinuria after the 20th week of gestation. Preeclampsia is a systemic disease with multiorgan involvement, and it is associated with a high risk of maternal and fetal morbidity and mortality. To date its pathogenesis is not completely understood, but placental hypoxia or hypoxia/reoxigenation may be the basic condition leading to systemic inflammation and endothelial dysfunction that induce all the clinical manifestations of the disorder. Delivery is the only curative treatment. Indeed, for the management of preeclampsia one needs to consider both the maternal risks due to continued pregnancy and the fetal risks associated with induced preterm delivery.

Platelet Disorders

2015 ◽  
Author(s):  
Lawrence L K Leung ◽  
James L. Zehnder
Keyword(s):  
Platelet Function ◽  
Clinical Manifestations ◽  
Von Willebrand Disease ◽  
Drug Induced ◽  
Excessive Bleeding ◽  
Vascular Integrity ◽  
Patient Reports ◽  
Platelet Function Disorders ◽  
Hemorrhagic Disorders ◽  
Von Willebrand

A bleeding disorder may be suspected when a patient reports spontaneous or excessive bleeding or bruising, often secondary to trauma. Possible causes can vary between abnormal platelet number or function, abnormal vascular integrity, coagulation defects, fibrinolysis, or a combination thereof. This review addresses hemorrhagic disorders associated with quantitative or qualitative platelet abnormalities, such as thrombocytopenia, platelet function disorders, thrombocytosis and thrombocythemia, and vascular purpuras. Hemorrhagic dis­orders associated with abnormalities in coagulation (e.g., von Willebrand disease and hemophilia) are not covered. An algorithm shows evidence-based practice guidelines for the management of immune thrombocytopenic purpura. Tables list questions regarding bleeding and bruising to ask patients, clinical manifestations of hemorrhagic disorders, typical results of tests for hemostatic function in bleeding disorders, causes of thrombocytopenia, other forms of drug-induced thrombocytopenia, classification of platelet function disorders, and selected platelet-modifying agents. This review contains ­1 highly rendered figure, 7 tables, and 82 references. 

scholarly journals Drug-Induced Heart Failure (Part 2: Mechanisms of Development, Clinical Signs, Differential Diagnosis, Risk Factors, Treatment and Prevention)

2020 ◽  
Vol 8 (2) ◽  
pp. 57-65
Author(s):  
O. D. Ostroumova ◽  
I. V. Goloborodova
Keyword(s):  
Heart Failure ◽  
Beta Blockers ◽  
Clinical Signs ◽  
Clinical Manifestations ◽  
Left Ventricular ◽  
Clinical Syndrome ◽  
Channel Blockers ◽  
Drug Induced ◽  
Treatment And Prevention ◽  
Developing Heart

Heart failure is a complex clinical syndrome caused by an impaired pumping function of the heart muscle, etiologically associated with cardiovascular disease and, in the vast majority of cases, requiring complex therapeutic regimens and simultaneous prescription of several drugs. To date, we know several classes of drugs (including those used for heart failure) which can induce development/progression of heart failure in both patients with left ventricular dysfunction, and in patients who do not have cardiovascular diseases. The aim of the study was to analyse and systematize data on development mechanisms, as well as methods of prevention and treatment of drug-induced heart failure when using diff erent groups of drugs. It has been established that drug-induced heart failure is most often associated with the use of calcium channel blockers (verapamil, diltiazem, nifedipine), beta-blockers, antiarrhythmic drugs (disopyramide, fl ecainide, propafenone, amiodarone, ibutilide, dofetilide, dronedarone), anthracyclines (doxorubicin) and other antitumor drugs (trastuzumab, bevacizumab, infl iximab), hypoglycemic drugs (thiazolidinediones, saxagliptin, alogliptin), and nonsteroidal anti-infl ammatory drugs, including selective cyclooxygenase-2 inhibitors. The study revealed various mechanisms of heart failure development following drug treatment. In some patients, heart failure development is associated with the cardiotoxic eff ect of a particular drug, in others with adverse eff ects on hemodynamics. Much depends on risks of developing heart failure, including specifi c risks attributable to groups of drugs and individual drugs. The identifi cation of drugs that can contribute to the development/ progression of heart failure, and possible clinical manifestations of drug-induced heart failure, as well as provision of timely information to physicians, and engagement of clinical pharmacologists with the aim of optimizing treatment of patients can facilitate timely diagnosis, treatment and prevention of drug-induced heart failure. 

scholarly journals Association between Endoscopic Findings Vs. Serology Findings of Patients with Suspected Celiac Disease

2021 ◽  
pp. 301-307
Author(s):  
Anwar Hussain Abbasi ◽  
Khawaja Ishfaq Ahmed ◽  
Nadeem Yousuf ◽  
Mahjabeen Fatima Qureshi ◽  
Muhammad Shahzeb Shaikh ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Chronic Diarrhea ◽  
Villous Atrophy ◽  
Clinical Manifestations ◽  
Final Analysis ◽  
Normal Mucosa ◽  
Diagnostic Value ◽  
Endoscopic Evaluation ◽  
Drug Induced ◽  
Endoscopic Findings

Objective: To determine the association between endoscopic findings vs. serology findings of patients with suspected celiac disease Methods: All the suspected cases (based on their clinical manifestations) of celiac disease were initially recruited having age >14 years and <40 years of both gender. Patients who did not willing to participate, patients already taking gluten diet for more than 3 months, patients with other causes of chronic diarrhea and alternate diagnosis like thyrotoxicosis, whipple’s disease, giardiasis, patients with drug induced diarrhea, patients in whom we cannot perform endoscopy, pregnant women, and patients already diagnosed cases of celiac disease were excluded from this study. Celiac disease was confirmed based on positive anti-tTG antibodies. Endoscopic evaluation of duodenum was performed in all positive cases. Results: A total of 50 patients were recruited for final analysis. Diagnostic accuracy of endoscopy was 34.6%. Young population (31.14±6.07 years) with females predominance (72%, n=36) were more common than males. The most common symptoms were presence of chronic diarrhea (74%, n=37) followed by abdominal pain (52%, n=26), nausea & vomiting (34%, n=17), and least common was presence of constipation (2%, n=1). On endoscopic evaluation, out of 50 positive anti-tTG antibodies cases, 24 had normal mucosa while partial villous atrophy observed in 15 (30%) cases and total villous atrophy observed in 11 cases (22%). Conclusions: Celiac disease was more prevalent in young females and patients usually presents with history of chronic diarrhea. Anti-tTG antibodies have more diagnostic value than duodenal endoscopy. Villous atrophy was found in more than 50% of the patients who were diagnosed with celiac disease.

scholarly journals To study the rate of HIV Sero-positivity in paediatric patients with high risk clinical profile

2018 ◽  
Vol 6 (7) ◽  
pp. 2318
Author(s):  
Tarsem Singh ◽  
Navreet Kaur Natt ◽  
Sneh Prabha Goel
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Clinical Manifestations ◽  
Failure To Thrive ◽  
Clinical Profile ◽  
Pediatric Hiv ◽  
Hiv Positive ◽  
Chronic Diarrhoea ◽  
Hiv Seropositivity ◽  
Clinical Risk

Background: Understanding the magnitude and clinical profile of pediatric HIV is essential for the clinicians and policy makers. The study was aimed to determine the rate of HIV seropositivity in pediatric patients with high risk clinical profile, study the clinical presentations and the mode of transmission of HIV in children.Methods: This prospective hospital-based study to screen 244 children aged 18 months to 12 years with high risk clinical profile for HIV seropositivity was carried out for a period of 1 year.Results: Of the 244 children screened, the commonest clinical features associated with high risk profile were failure to thrive in 200 (81.97%), persistent fever in 151 (61.89%), chronic diarrhoea in 76 (31.15%), cough >1month 112 (45.90%) patients. HIV seropositivity was reported in 11/244 (4.51%) patients; with failure to thrive in 10/11 (90.90%), chronic diarrhoea in 09/11 (81.81%), seborrheic dermatitis in 2/11 (18.18%) patients followed by persistent cough, severe malnutrition, oral thrush, generalized lymphadenopathy and recurrent bacterial skin infections in 1 patient each out of 11(9.09%). Chronic diarrhoea was a significant independent clinical risk factor for predicting HIV seropositivity (Chi2 = 13.81, p<0.001, Odds ratio=11.15). The probability of HIV seropositivity increased significantly with the number of risk factors concomitantly present, with 30% seropositivity in those with four clinical risk factors (Chi2 =32.89, D. F=1, P<0.001). The parents of all seropositive children were seropositive.Conclusions: The probability of HIV infection in a child depends upon the nature and number of clinical manifestations present. All HIV positive children h HIV positive parents in this study indicating vertical transmission.

scholarly journals The Relationship between Hemophilia A Severity and Hemophilia Activities List

2021 ◽  
Author(s):  
Faizal Muhammad
Keyword(s):  
High Risk ◽  
Hemophilia A ◽  
Bleeding Event ◽  
Clinical Manifestations ◽  
Self Care ◽  
Daily Activities ◽  
Clotting Factors ◽  
Household Tasks ◽  
The Relationship ◽  
Lying Down

Hemophilia is a hereditary bleeding disorder due to clotting factors deficiency. Its clinical manifestations including spontaneous and recurrent joints and muscle bleeding. Thus, hemophilia can limit the patients’ daily activities. This study aims to assess the relationship of hemophilia A severity on daily activities and the Hemophilia Activities List (HAL). The research subjects were thirty men with hemophilia A aged 18 years old or older who went to the Hematology-Oncology Clinic of Dr. Moewardi General Hospital during February - September 2020. Standardized seven aspects of routine activities with high-risk for bleeding event were assessed using the HAL questionnaire including lying down/ sitting/ kneeling/ standing, functions of the legs, functions of the arms, use of transportation, self-care, household tasks, leisure activities and sports. Based on the frequency of activity difficulty due to hemophilia A, each average score of HAL aspect was categorized into never (100% - 76%); rarely (75% - 51%), sometimes (50% - 26%), and impossible (25% - 0%). Based on Factor VIII level, hemophilia A severity was categorized into mild, moderate, and severe. Spearman’s correlation test was used for statistical analysis. The result showed significant correlation (p &lt; 0.05) on five aspects, including lying down/ sitting/ kneeling/ standing, functions of the legs, use of transportation, self-care, and household tasks. The aspects of arms functions and leisure sports activities were not significantly correlated (p &gt; 0.05). Nevertheless, these two aspects showed positive sufficient (r = 0.330) and weak (r = 0.177) correlation respectively. Joint and muscle bleeding are an undeniable pathological event in hemophilia patients. Hemophilia A severity positively correlates with the bleeding event frequency in the essential routine musculoskeletal activities. According to the HAL questionnaire, it needs to be a concern for clinicians and patient education to prevent bleeding in any high-risk musculoskeletal activities.

Sign in / Sign up

Export Citation Format

Share Document