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1
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Xiao Y, Powell DW, Liu X, Li Q. Cardiovascular manifestations of inflammatory bowel diseases and the underlying pathogenic mechanisms. Am J Physiol Regul Integr Comp Physiol 2023; 325:R193-R211. [PMID: 37335014 PMCID: PMC10979804 DOI: 10.1152/ajpregu.00300.2022] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Revised: 06/01/2023] [Accepted: 06/01/2023] [Indexed: 06/21/2023]
Abstract
Inflammatory bowel disease (IBD), consisting of ulcerative colitis and Crohn's disease, mainly affects the gastrointestinal tract but is also known to have extraintestinal manifestations because of long-standing systemic inflammation. Several national cohort studies have found that IBD is an independent risk factor for the development of cardiovascular disorders. However, the molecular mechanisms by which IBD impairs the cardiovascular system are not fully understood. Although the gut-heart axis is attracting more attention in recent years, our knowledge of the organ-to-organ communication between the gut and the heart remains limited. In patients with IBD, upregulated inflammatory factors, altered microRNAs and lipid profiles, as well as dysbiotic gut microbiota, may induce adverse cardiac remodeling. In addition, patients with IBD have a three- to four times higher risk of developing thrombosis than people without IBD, and it is believed that the increased risk of thrombosis is largely due to increased procoagulant factors, platelet count/activity, and fibrinogen concentration, in addition to decreased anticoagulant factors. The predisposing factors for atherosclerosis are present in IBD and the possible mechanisms may involve oxidative stress system, overexpression of matrix metalloproteinases, and changes in vascular smooth muscle phenotype. This review focuses mainly on 1) the prevalence of cardiovascular diseases associated with IBD, 2) the potential pathogenic mechanisms of cardiovascular diseases in patients with IBD, and 3) adverse effects of IBD drugs on the cardiovascular system. Also, we introduce here a new paradigm for the gut-heart axis that includes exosomal microRNA and the gut microbiota as a cause for cardiac remodeling and fibrosis.
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Affiliation(s)
- Ying Xiao
- Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, China
- Division of Gastroenterology, Department of Internal Medicine, University of Texas Medical Branch at Galveston, Galveston, Texas, United States
| | - Don W Powell
- Division of Gastroenterology, Department of Internal Medicine, University of Texas Medical Branch at Galveston, Galveston, Texas, United States
| | - Xiaowei Liu
- Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, China
| | - Qingjie Li
- Division of Gastroenterology, Department of Internal Medicine, University of Texas Medical Branch at Galveston, Galveston, Texas, United States
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2
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Investigation of doxorubicin combined with ciprofloxacin-induced cardiotoxicity: from molecular mechanism to fundamental heart function. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2022:10.1007/s00210-022-02331-2. [DOI: 10.1007/s00210-022-02331-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Accepted: 11/07/2022] [Indexed: 11/25/2022]
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3
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Li S, Chen Z, Huang L, Liu Z, Shi Y, Zhang M, Li H, Zeng L, Ni J, Zhu Y, Jia ZJ, Cheng G, Zhang L. Safety of Quinolones in Children: A Systematic Review and Meta-Analysis. Paediatr Drugs 2022; 24:447-464. [PMID: 35771411 DOI: 10.1007/s40272-022-00513-2] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/25/2022] [Indexed: 01/01/2023]
Abstract
BACKGROUND The results of animal experiments show that quinolone antibacterial drugs may permanently damage the soft tissues of the weight-bearing joints of young animals. Out of safety concerns, using quinolones in children has always been controversial. OBJECTIVE The aim of this study was to assess the risk of using quinolones in children and provide evidence for clinicians to support decision making. DATA SOURCES The MEDLINE (Ovid), EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), International Pharmaceutical Abstracts (Ovid), CINAHL, CNKI, VIP, and WanFang Data databases were searched from inception to 8 September 2021. STUDY SELECTION All types of studies that reported the safety data of quinolones in children, including clinical trials and observational studies. DATA EXTRACTION Data extraction and cross-checking were completed by two independent reviewers using a pilot-tested standardized data extraction form. RESULTS The overall incidence rate of adverse drug events (ADEs) in children using systemic quinolones was 5.39% and the most common ADEs were gastrointestinal reactions (incidence rate, 2.02%). Quinolone-induced musculoskeletal ADEs in children were uncommon (0.76%). Meta-analysis results showed that the risk of musculoskeletal ADEs in children using quinolones was higher than children in the control group (51 studies; rate ratio [RR] 2.03, 95% confidence interval [CI] 1.82-2.26; p < 0.001; I2 = 18.6%; moderate-quality evidence). However, the subgroup analysis results showed that differences might only be observed in children who were followed up for 2 months to 1 year (2-6 months: RR 2.56, 95% CI 2.26-2.89; 7 months to 1 year: RR 1.35, 95% CI 0.98-1.86). Moreover, children (adolescents) aged between 13 and 18 years might be sensitive to the musculoskeletal toxicity of quinolones (RR 2.69, 95% CI 2.37-3.05; moderate-quality evidence) and the risk of levofloxacin-induced musculoskeletal ADEs might be higher (RR 1.33, 95% CI 1.00-1.77; low-quality evidence). CONCLUSIONS Although the existing evidence shows that quinolone-induced musculoskeletal ADEs seem to be only short-term and reversible, and no serious skeletal and muscular system damage cases have been reported in children, quinolones should be avoided unless necessary in children because the incidence rate of quinolone-related ADEs is not low and they are broad-spectrum antibiotics that will induce the emergence of resistant strains if used frequently.
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Affiliation(s)
- Siyu Li
- Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, 610041, China
- Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, 610041, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Chengdu, 610041, China
- West China School of Medicine, Sichuan University, Chengdu, 610041, China
| | - Zhe Chen
- Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, 610041, China
- Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, 610041, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Chengdu, 610041, China
| | - Liang Huang
- Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, 610041, China
- Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, 610041, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Chengdu, 610041, China
| | - Zheng Liu
- Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, 610041, China
- Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, 610041, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Chengdu, 610041, China
- West China School of Medicine, Sichuan University, Chengdu, 610041, China
| | - Yuqing Shi
- Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, 610041, China
- Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, 610041, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Chengdu, 610041, China
- West China School of Pharmacy, Sichuan University, Chengdu, 610041, China
| | - Miao Zhang
- Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, 610041, China
- Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, 610041, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Chengdu, 610041, China
- West China School of Pharmacy, Sichuan University, Chengdu, 610041, China
| | - Hailong Li
- Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, 610041, China
- Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, 610041, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Chengdu, 610041, China
| | - Linan Zeng
- Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, 610041, China
- Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, 610041, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Chengdu, 610041, China
| | - Jiaqi Ni
- Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, 610041, China
- Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, 610041, China
- West China School of Pharmacy, Sichuan University, Chengdu, 610041, China
| | - Yu Zhu
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, 610041, China
| | - Zhi-Jun Jia
- Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, 610041, China
- Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, 610041, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Chengdu, 610041, China
- West China School of Pharmacy, Sichuan University, Chengdu, 610041, China
| | - Guo Cheng
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Chengdu, 610041, China
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, 610041, China
- Laboratory of Molecular Translational Medicine, Center for Translational Medicine, Sichuan University, Chengdu, 610041, China
| | - Lingli Zhang
- Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, 610041, China.
- Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, 610041, China.
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Chengdu, 610041, China.
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Elgassim MAM, Saied ASS, Mustafa MA, Abdelrahman A, AlJaufi I, Salem W. A Rare Case of Metronidazole Overdose Causing Ventricular Fibrillation. Cureus 2022; 14:e24728. [PMID: 35676987 PMCID: PMC9166500 DOI: 10.7759/cureus.24728] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/27/2022] [Indexed: 11/25/2022] Open
Abstract
Ventricular fibrillation is not known as a complication of metronidazole poisoning. Although some arrhythmias have been reported as a complication of metronidazole intake while taking antiarrhythmic medications, most such arrhythmias are possibly related to co-ingestion of drugs with metronidazole as it affects the metabolism of these drugs. In this case, ventricular fibrillation occurred in a young patient without preexisting medical conditions or any other known drug ingestion, which was never been reported before. We present a case of an 18-year-old male brought in by the ambulance service after attempting to end his life by overdosing on metronidazole. While being transported he developed ventricular fibrillation and received an electric shock, which reverted the episode. Laboratory investigations did not show any clear cause that might have precipitated his arrhythmia.
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Han Y, Ma Y, Yao S, Zhang J, Hu C. In vivo and in silico evaluations of survival and cardiac developmental toxicity of quinolone antibiotics in zebrafish embryos (Danio rerio). ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2021; 277:116779. [PMID: 33640819 DOI: 10.1016/j.envpol.2021.116779] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/17/2020] [Revised: 01/25/2021] [Accepted: 02/15/2021] [Indexed: 06/12/2023]
Abstract
Quinolones are ranked as the second most commonly used class of antibiotics in China, despite their adverse clinical and environmental effects. However, information on their cardiac developmental toxicity to zebrafish is limited. This study investigates the relationships between different quinolone structures and toxicity in zebrafish embryos using in vivo and in silico methods. All of the experimentally tested quinolones show cardiac developmental toxicity potential and present mortality and teratogenic effects in a dose-dependent manner. Theoretically, the acute toxicity values predicted using quantitative structure-toxicity relationship (QSTR) modeling based on previously reported LC50 values are in good agreement with the in vivo results. Further investigation demonstrates that the hormetic concentration response of some quinolones may be related to methylation on the piperazine ring at the C-7 position. The amino group at the C-5 position, the methylated or ethylated piperazine group at the C-7 position, halogens at the C-8 position and a cyclopropyl ring at N1 position may be responsible for cardiac developmental toxicity. In terms of survival (key ecological endpoint), the naridine ring is more toxic than the quinoline ring. This combined approach can predict the acute and cardiac developmental toxicity of other quinolones and impurities.
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Affiliation(s)
- Ying Han
- Division of Antibiotics, Institute for Chemical Drug Control, National Institutes for Food and Drug Control, Beijing, 102629, China
| | - Yuanyuan Ma
- Department of Pharmacology, NHC Key Laboratory of Biotechnology of Antibiotics, Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China
| | - Shangchen Yao
- Division of Antibiotics, Institute for Chemical Drug Control, National Institutes for Food and Drug Control, Beijing, 102629, China
| | - Jingpu Zhang
- Department of Pharmacology, NHC Key Laboratory of Biotechnology of Antibiotics, Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
| | - Changqin Hu
- Division of Antibiotics, Institute for Chemical Drug Control, National Institutes for Food and Drug Control, Beijing, 102629, China.
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Shojaei L, Ruzbahani M, Khajavian S, Shahsavari S, Tamasoki N, Rajabian M, Moradi F, Shahbazi F. Analysis of QTc Interval during Levofloxacin Prescription in Cardiac Patients with Pneumonia. Curr Drug Saf 2020; 15:111-116. [DOI: 10.2174/1574886315666200213112702] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2019] [Revised: 12/03/2019] [Accepted: 12/05/2019] [Indexed: 11/22/2022]
Abstract
Background:
Medications induced QT prolongation could cause ventricular arrhythmia,
torsade de pointes, and death.
Objective:
The purpose of this study was to evaluate the magnitude of QTc interval prolongation as
a result of levofloxacin treatment in patients admitted to cardiology wards.
Methods:
This was a cross-sectional study conducted in the coronary care units and general wards
of the Imam Ali Heart Hospital in Kermanshah, Iran. The QTc interval was determined at baseline
and after 72 hours of levofloxacin administration. Changes in the QTc interval before and after the
levofloxacin prescription were determined.
Results:
The mean age of recruited patients was 63.26 ± 14.56 years. More than 80% of patients
who received levofloxacin experienced QTc prolongation. The QTc interval was increased significantly
after levofloxacin administration (15.68 ± 26.84 milliseconds) (p<0.001). These changes remained
significant after excluding medications with QTc lengthening properties (p<0.001).
Conclusion:
Treatment with levofloxacin in patients with heart disease increases the risk of QT
prolongation.
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Affiliation(s)
- Lida Shojaei
- Pharmaceutical Sciences Research Center, School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Mohammad Ruzbahani
- Imam Ali cardiovascular Hospital, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Shiva Khajavian
- Imam Ali cardiovascular Hospital, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Soodeh Shahsavari
- School of Allied Medical Sciences, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Negin Tamasoki
- Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Mina Rajabian
- Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Farzaneh Moradi
- Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Foroud Shahbazi
- Pharmaceutical Sciences Research Center, School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran
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7
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Gawałko M, Balsam P, Lodziński P, Grabowski M, Krzowski B, Opolski G, Kosiuk J. Cardiac Arrhythmias in Autoimmune Diseases. Circ J 2020; 84:685-694. [PMID: 32101812 DOI: 10.1253/circj.cj-19-0705] [Citation(s) in RCA: 58] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Autoimmune diseases (ADs) affect approximately 10% of the world's population. Because ADs are frequently systemic disorders, cardiac involvement is common. In this review we focus on typical arrhythmias and their pathogenesis, arrhythmia-associated mortality, and possible treatment options among selected ADs (sarcoidosis, systemic lupus erythematosus, scleroderma, type 1 diabetes, Graves' disease, rheumatoid arthritis, ankylosing spondylitis [AS], psoriasis, celiac disease [CD], and inflammatory bowel disease [IBD]). Rhythm disorders have different underlying pathophysiologies; myocardial inflammation and fibrosis seem to be the most important factors. Inflammatory processes and oxidative stress lead to cardiomyocyte necrosis, with subsequent electrical and structural remodeling. Furthermore, chronic inflammation is the pathophysiological basis linking AD to autonomic dysfunction, including sympathetic overactivation and a decline in parasympathetic function. Autoantibody-mediated inhibitory effects of cellular events (i.e., potassium or L-type calcium currents, M2muscarinic cholinergic or β1-adrenergic receptor signaling) can also lead to cardiac arrhythmia. Drug-induced arrhythmias, caused, for example, by corticosteroids, methotrexate, chloroquine, are also observed among AD patients. The most common arrhythmia in most AD presentations is atrial arrhythmia (primarily atrial fibrillation), expect for sarcoidosis and scleroderma, which are characterized by a higher burden of ventricular arrhythmia. Arrhythmia-associated mortality is highest among patients with sarcoidosis and lowest among those with AS; there are scant data related to mortality in patients with psoriasis, CD, and IBD.
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Affiliation(s)
- Monika Gawałko
- 1st Chair and Department of Cardiology, Medical University of Warsaw
| | - Paweł Balsam
- 1st Chair and Department of Cardiology, Medical University of Warsaw
| | - Piotr Lodziński
- 1st Chair and Department of Cardiology, Medical University of Warsaw
| | - Marcin Grabowski
- 1st Chair and Department of Cardiology, Medical University of Warsaw
| | - Bartosz Krzowski
- 1st Chair and Department of Cardiology, Medical University of Warsaw
| | - Grzegorz Opolski
- 1st Chair and Department of Cardiology, Medical University of Warsaw
| | - Jędrzej Kosiuk
- 1st Chair and Department of Cardiology, Medical University of Warsaw.,Department of Electrophysiology, Helios Klinikum Koethen
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Nitzan O, Elias M, Peretz A, Saliba W. Role of antibiotics for treatment of inflammatory bowel disease. World J Gastroenterol 2016; 22:1078-1087. [PMID: 26811648 PMCID: PMC4716021 DOI: 10.3748/wjg.v22.i3.1078] [Citation(s) in RCA: 184] [Impact Index Per Article: 20.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2015] [Revised: 07/06/2015] [Accepted: 11/13/2015] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel disease is thought to be caused by an aberrant immune response to gut bacteria in a genetically susceptible host. The gut microbiota plays an important role in the pathogenesis and complications of the two main inflammatory bowel diseases: Crohn’s disease (CD) and ulcerative colitis. Alterations in gut microbiota, and specifically reduced intestinal microbial diversity, have been found to be associated with chronic gut inflammation in these disorders. Specific bacterial pathogens, such as virulent Escherichia coli strains, Bacteroides spp, and Mycobacterium avium subspecies paratuberculosis, have been linked to the pathogenesis of inflammatory bowel disease. Antibiotics may influence the course of these diseases by decreasing concentrations of bacteria in the gut lumen and altering the composition of intestinal microbiota. Different antibiotics, including ciprofloxacin, metronidazole, the combination of both, rifaximin, and anti-tuberculous regimens have been evaluated in clinical trials for the treatment of inflammatory bowel disease. For the treatment of active luminal CD, antibiotics may have a modest effect in decreasing disease activity and achieving remission, and are more effective in patients with disease involving the colon. Rifamixin, a non absorbable rifamycin has shown promising results. Treatment of suppurative complications of CD such as abscesses and fistulas, includes drainage and antibiotic therapy, most often ciprofloxacin, metronidazole, or a combination of both. Antibiotics might also play a role in maintenance of remission and prevention of post operative recurrence of CD. Data is more sparse for ulcerative colitis, and mostly consists of small trials evaluating ciprofloxacin, metronidazole and rifaximin. Most trials did not show a benefit for the treatment of active ulcerative colitis with antibiotics, though 2 meta-analyses concluded that antibiotic therapy is associated with a modest improvement in clinical symptoms. Antibiotics show a clinical benefit when used for the treatment of pouchitis. The downsides of antibiotic treatment, especially with recurrent or prolonged courses such as used in inflammatory bowel disease, are significant side effects that often cause intolerance to treatment, Clostridium dificile infection, and increasing antibiotic resistance. More studies are needed to define the exact role of antibiotics in inflammatory bowel diseases.
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Luo F, Gu J, Chen L, Xu X. Molecular docking and molecular dynamics studies on the structure-activity relationship of fluoroquinolone for the HERG channel. MOLECULAR BIOSYSTEMS 2015; 10:2863-9. [PMID: 25100024 DOI: 10.1039/c4mb00396a] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Fluoroquinolones play an important role in the treatment of serious bacterial infections, but at the same time they could lead to cardiac toxicity due to the blockage of the HERG potassium channel, which even leads to the withdrawal of some fluoroquinolones. Blockage of the HERG potassium channel by drugs or drug-like compounds has become a critical problem in drug discovery. Though there were large amounts of bioactivity data of fluoroquinolones on the blockage of HERG, little structural basis of binding of blockers to the HERG channel was known. Here, we combined molecular docking, molecular dynamics simulations, free energy calculations and binding energy decomposition analysis to explore the binding modes of fluoroquinolones in the HERG potassium channel. The calculated binding free energies were consistent with the experimental binding affinities. Our results showed that the CH3 group in MX was favorable for the binding to the HERG channel, while Tyr652 and Phe656 were critical for the hydrophobic interaction between fluoroquinolones and the HERG channel. We expected that our results of calculation could provide important insights for the rational design and discovery of drugs.
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Affiliation(s)
- Fang Luo
- Beijing National Laboratory for Molecular Sciences, State Key Lab of Rare Earth Material Chemistry and Applications, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, P. R. China.
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10
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Antoniou T, Hollands S, Macdonald EM, Gomes T, Mamdani MM, Juurlink DN. Trimethoprim-sulfamethoxazole and risk of sudden death among patients taking spironolactone. CMAJ 2015; 187:E138-E143. [PMID: 25646289 DOI: 10.1503/cmaj.140816] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022] Open
Abstract
BACKGROUND Trimethoprim-sulfamethoxazole increases the risk of hyperkalemia when used with spironolactone. We examined whether this drug combination is associated with an increased risk of sudden death, a consequence of severe hyperkalemia. METHODS We conducted a population-based nested case-control study involving Ontario residents aged 66 years or older who received spironolactone between Apr. 1, 1994, and Dec. 31, 2011. Within this group, we identified cases as patients who died of sudden death within 14 days after receiving a prescription for trimethoprim-sulfamethoxazole or one of the other study antibiotics (amoxicillin, ciprofloxacin, norfloxacin or nitrofurantoin). For each case, we identified up to 4 controls matched by age and sex. We determined the odds ratio (OR) for the association between sudden death and exposure to each antibiotic relative to amoxicillin, adjusted for predictors of sudden death using a disease risk index. RESULTS Of the 11,968 patients who died of sudden death while receiving spironolactone, we identified 328 whose death occurred within 14 days after antibiotic exposure. Compared with amoxicillin, trimethoprim-sulfamethoxazole was associated with a more than twofold increase in the risk of sudden death (adjusted OR 2.46, 95% confidence interval [CI] 1.55-3.90). Ciprofloxacin (adjusted OR 1.55, 95% CI 1.02-2.38) and nitrofurantoin (adjusted OR 1.70, 95% CI 1.03-2.79) were also associated with an increased risk of sudden death, although the risk with nitrofurantoin was not apparent in a sensitivity analysis. INTERPRETATION The antibiotic trimethoprim-sulfamethoxazole was associated with an increased risk of sudden death among older patients taking spironolactone. When clinically appropriate, alternative antibiotics should be considered in these patients.
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Affiliation(s)
- Tony Antoniou
- Department of Family and Community Medicine (Antoniou), Li Ka Shing Knowledge Institute (Antoniou, Gomes, Mamdani), St. Michael's Hospital; University of Toronto (Gomes, Mamdani, Juurlink); Institute for Clinical Evaluative Sciences (Antoniou, Hollands, Macdonald, Gomes, Mamdani, Juurlink); Sunnybrook Research Institute (Juurlink), Toronto, Ont.
| | - Simon Hollands
- Department of Family and Community Medicine (Antoniou), Li Ka Shing Knowledge Institute (Antoniou, Gomes, Mamdani), St. Michael's Hospital; University of Toronto (Gomes, Mamdani, Juurlink); Institute for Clinical Evaluative Sciences (Antoniou, Hollands, Macdonald, Gomes, Mamdani, Juurlink); Sunnybrook Research Institute (Juurlink), Toronto, Ont
| | - Erin M Macdonald
- Department of Family and Community Medicine (Antoniou), Li Ka Shing Knowledge Institute (Antoniou, Gomes, Mamdani), St. Michael's Hospital; University of Toronto (Gomes, Mamdani, Juurlink); Institute for Clinical Evaluative Sciences (Antoniou, Hollands, Macdonald, Gomes, Mamdani, Juurlink); Sunnybrook Research Institute (Juurlink), Toronto, Ont
| | - Tara Gomes
- Department of Family and Community Medicine (Antoniou), Li Ka Shing Knowledge Institute (Antoniou, Gomes, Mamdani), St. Michael's Hospital; University of Toronto (Gomes, Mamdani, Juurlink); Institute for Clinical Evaluative Sciences (Antoniou, Hollands, Macdonald, Gomes, Mamdani, Juurlink); Sunnybrook Research Institute (Juurlink), Toronto, Ont
| | - Muhammad M Mamdani
- Department of Family and Community Medicine (Antoniou), Li Ka Shing Knowledge Institute (Antoniou, Gomes, Mamdani), St. Michael's Hospital; University of Toronto (Gomes, Mamdani, Juurlink); Institute for Clinical Evaluative Sciences (Antoniou, Hollands, Macdonald, Gomes, Mamdani, Juurlink); Sunnybrook Research Institute (Juurlink), Toronto, Ont
| | - David N Juurlink
- Department of Family and Community Medicine (Antoniou), Li Ka Shing Knowledge Institute (Antoniou, Gomes, Mamdani), St. Michael's Hospital; University of Toronto (Gomes, Mamdani, Juurlink); Institute for Clinical Evaluative Sciences (Antoniou, Hollands, Macdonald, Gomes, Mamdani, Juurlink); Sunnybrook Research Institute (Juurlink), Toronto, Ont
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11
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Fralick M, Macdonald EM, Gomes T, Antoniou T, Hollands S, Mamdani MM, Juurlink DN. Co-trimoxazole and sudden death in patients receiving inhibitors of renin-angiotensin system: population based study. BMJ 2014; 349:g6196. [PMID: 25359996 PMCID: PMC4214638 DOI: 10.1136/bmj.g6196] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
OBJECTIVE To determine whether the prescription of co-trimoxazole with an angiotensin converting enzyme inhibitor or angiotensin receptor blocker is associated with sudden death. DESIGN Population based nested case-control study. SETTING Ontario, Canada, from 1 April 1994 to 1 January 2012. PARTICIPANTS Ontario residents aged 66 years or older treated with an angiotensin converting enzyme inhibitor or angiotensin receptor blocker. Cases were those who died suddenly shortly after receiving an outpatient prescription for one of co-trimoxazole, amoxicillin, ciprofloxacin, norfloxacin, or nitrofurantoin. Each case was matched with up to four controls on age, sex, chronic kidney disease, and diabetes. MAIN OUTCOME MEASURE Odds ratio for the association between sudden death and exposure to each antibiotic relative to amoxicillin, after adjustment for predictors of sudden death according to a disease risk index. RESULTS Of 39,879 sudden deaths, 1027 occurred within seven days of exposure to an antibiotic and were matched to 3733 controls. Relative to amoxicillin, co-trimoxazole was associated with an increased risk of sudden death (adjusted odds ratio 1.38, 95% confidence interval 1.09 to 1.76). The risk was marginally higher at 14 days (adjusted odds ratio 1.54, 1.29 to 1.84). This corresponds to approximately three sudden deaths within 14 days per 1000 co-trimoxazole prescriptions. Ciprofloxacin (a known cause of QT interval prolongation) was also associated with an increased risk of sudden death (adjusted odds ratio 1.29, 1.03 to 1.62), but no such risk was observed with nitrofurantoin or norfloxacin. CONCLUSIONS In older patients receiving angiotensin converting enzyme inhibitors or angiotensin receptor blockers, co-trimoxazole is associated with an increased risk of sudden death. Unrecognized severe hyperkalemia may underlie this finding. When appropriate, alternative antibiotics should be considered in such patients.
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Affiliation(s)
- Michael Fralick
- Department of Internal Medicine, University of Toronto, Toronto, ON, Canada, M5G 2C4
| | - Erin M Macdonald
- Institute for Clinical Evaluative Sciences, Toronto, ON, Canada, M5N 4M5
| | - Tara Gomes
- Institute for Clinical Evaluative Sciences, Toronto, ON, Canada, M5N 4M5 Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, ON, Canada, M5B 1W8 Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada, M5T 3M7
| | - Tony Antoniou
- Institute for Clinical Evaluative Sciences, Toronto, ON, Canada, M5N 4M5 Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, ON, Canada, M5B 1W8 Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada, M5T 3M7 Department of Family and Community Medicine, St Michael's Hospital, Toronto
| | - Simon Hollands
- Institute for Clinical Evaluative Sciences, Toronto, ON, Canada, M5N 4M5
| | - Muhammad M Mamdani
- Institute for Clinical Evaluative Sciences, Toronto, ON, Canada, M5N 4M5 Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, ON, Canada, M5B 1W8 Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada, M5T 3M7 Applied Health Research Centre, St Michael's Hospital, Toronto King Saud University, Riyadh, Saudi Arabia
| | - David N Juurlink
- Institute for Clinical Evaluative Sciences, Toronto, ON, Canada, M5N 4M5 Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, ON, Canada, M5B 1W8 Sunnybrook Research Institute, Toronto, ON, Canada, M4N 3M5 Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada, M5T 3M7
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Toxicological assessment of trace β-diketone antibiotic mixtures on zebrafish (Danio rerio) by proteomic analysis. PLoS One 2014; 9:e102731. [PMID: 25062015 PMCID: PMC4111491 DOI: 10.1371/journal.pone.0102731] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2014] [Accepted: 06/21/2014] [Indexed: 02/06/2023] Open
Abstract
β-Diketone antibiotics (DKAs) can produce chronic toxicity in aquatic ecosystems due to their pseudo-persistent in the environment. In this study, after long-term DKA exposure to zebrafish (Danio rerio), 47 protein spots had greater than 2-fold differential expression as compared to the control; there were 26 positive proteins with 14 up-regulated and 12 down-regulated. The main functions of the differentially expressed proteins were related to signal transduction mechanisms and the cytoskeleton. Of the 26 target genes, 11 genes were consistent between their transcriptional and translational levels. Low dose DKA exposure (4.69 and 9.38 mg/L) stimulated spontaneous movement in zebrafish. Changes in both creatine kinase activity and creatine concentration showed a similar trend to zebrafish activity. There was no obvious change in SV-BA after DKA exposure, while a reduction of heart rate was concomitant with increasing DKA concentrations. DKAs also induced severe histopathological changes in zebrafish heart tissue, such as dissolution of cristae and vacuolation of mitochondria. These results demonstrated that trace-level DKA exposure affects a variety of cellular and biological processes in zebrafish.
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Lapi F, Wilchesky M, Kezouh A, Benisty JI, Ernst P, Suissa S. Fluoroquinolones and the Risk of Serious Arrhythmia: A Population-Based Study. Clin Infect Dis 2012; 55:1457-65. [DOI: 10.1093/cid/cis664] [Citation(s) in RCA: 57] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
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[Severe bacterial infection: increased mortality in elderly women with low body weight taking drugs prolonging the QTc interval]. Med Klin Intensivmed Notfmed 2012; 107:275-84. [PMID: 22543817 DOI: 10.1007/s00063-012-0107-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2011] [Revised: 01/25/2012] [Accepted: 03/19/2012] [Indexed: 01/08/2023]
Abstract
AIMS Women have a higher risk of acquired long QT syndrome which could be of vital importance in severe bacterial infections when macrolides or fluoroquinolones are administered. This study evaluated whether age, drugs prolonging the QTc interval and body weight were additional influencing factors on mortality in the critically ill with respect to gender. METHODS In an exploratory investigation 204 intensive care unit (ICU) patients (78 f, 126 m, 61.1±16.1 years) with severe bacterial infections were studied (mortality probability model II(0) 49.1±28%). Antibiotic therapy was carried out following standard guidelines. In 65.2% of patients potentially QTc prolonging drugs were administered for ≥48 h. Body weight was ascertained on ICU admission. RESULTS By comparable severity of illness and comparable effect of antibiotic therapy, age, QTc prolonging drugs and less body weight showed significant effects on survival in women (p<0.001, 0.008 and 0.009, respectively). For women mortality increased with age ≥60 years (p=0.01). The division between survival versus non-survival was intensified by addition of QTc prolonging medication and body weight. As such a best risk assessment in women was achieved if age, QTc prolonging therapy and less body weight were combined (p<0.001). In a direct comparison to men, women with at least two of these factors had a significantly poorer outcome (OR 2.37; 95% CI 1.13-4.98; p=0.022). CONCLUSIONS Age, QTc prolonging drugs and lower body weight can additionally increase mortality in critically ill women. If negative outcome is attributed to a higher dosage, an adjustment for body weight must be carried out. Until now it should be considered whether it would be better to replace QTc prolonging antibiotics in routinely performed drug alternation in elderly lean women.
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Adikwu E, Brambaifa N. Ciprofloxacin Cardiotoxicity and Hepatotoxicity in Humans and Animals. ACTA ACUST UNITED AC 2012. [DOI: 10.4236/pp.2012.32028] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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Ibrahim M, Omar B. Ciprofloxacin-induced torsade de pointes. Am J Emerg Med 2012; 30:252.e5-9. [DOI: 10.1016/j.ajem.2010.09.039] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2010] [Accepted: 09/28/2010] [Indexed: 01/08/2023] Open
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Pugi A, Longo L, Bartoloni A, Rossolini GM, Mugelli A, Vannacci A, Lapi F. Cardiovascular and metabolic safety profiles of the fluoroquinolones. Expert Opin Drug Saf 2011; 11:53-69. [PMID: 21958023 DOI: 10.1517/14740338.2011.624512] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
INTRODUCTION Certain fluoroquinolones share similar indications of use. A comparison among Cardiovascular and metabolic (i.e., dysglycemia) safety profiles of the fluoroquinolones might be particularly useful for the prescribers' decision-making process as well as to hypothesize future researcher purposes. AREAS COVERED A literature search was conducted using keywords apt to identify information on safety profile of the fluoroquinolones. Publications concerned with descriptive and etiological surveys were manually reviewed. EXPERT OPINION Cardiac alterations and blood glucose impairments might be associated with any fluoroquinolone. However, the benefit/risk profile of these agents could be stratified for the single compounds. Several predisposing factors, such as diabetes, heart illnesses and their related pharmacotherapies, might exacerbate the risk of potentially serious adverse events. In this context, the opportunity of the more appropriate choice among different fluoroquinolones could be applicable.
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Affiliation(s)
- Alessandra Pugi
- University of Florence, Department of Pharmacology, Viale Pieraccini 6, 50139, Florence, Italy.
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Dogan Y, Soylu A, Eren GA, Poturoglu S, Dolapcioglu C, Sonmez K, Duman H, Sevindir I. Evaluation of QT and P wave dispersion and mean platelet volume among inflammatory bowel disease patients. Int J Med Sci 2011; 8:540-546. [PMID: 21960745 PMCID: PMC3180769 DOI: 10.7150/ijms.8.540] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2011] [Accepted: 08/02/2011] [Indexed: 01/17/2023] Open
Abstract
BACKGROUND In inflammatory bowel disease (IBD) number of thromboembolic events are increased due to hypercoagulupathy and platelet activation. Increases in mean platelet volume (MPV) can lead to platelet activation, this leads to thromboembolic events and can cause acute coronary syndromes. In IBD patients, QT-dispersion and P-wave dispersion are predictors of ventricular arrhythmias and atrial fibrilation; MPV is accepted as a risk factor for acute coronary syndromes, we aimed at evaluating the correlations of these with the duration of disease, its localization and activity. METHODS The study group consisted of 69 IBD (Ulcerative colitis n: 54, Crohn's Disease n: 15) patients and the control group included 38 healthy individuals. Disease activity was evaluated both endoscopically and clinically. Patients with existing cardiac conditions, those using QT prolonging medications and having systemic diseases, anemia and electrolyte imbalances were excluded from the study. QT-dispersion, P-wave dispersion and MPV values of both groups were compared with disease activity, its localization, duration of disease and the antibiotics used. RESULTS The P-wave dispersion values of the study group were significantly higher than those of the control group. Duration of the disease was not associated with QT-dispersion, and MPV levels. QT-dispersion, P-wave dispersion, MPV and platelet count levels were similar between the active and in mild ulcerative colitis patients. QT-dispersion levels were similar between IBD patients and the control group. No difference was observed between P-wave dispersion, QT-dispersion and MPV values; with regards to disease duration, disease activity, and localization in the study group (p>0.05). CONCLUSIONS P-wave dispersion which is accepted as a risk factor for the development of atrial fibirilation was found to be high in our IBD patients. This demonstrates us that the risk of developing atrial fibrillation may be high in patients with IBD. No significant difference was found in the QT-dispersion, and in the MPV values when compared to the control group.
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Affiliation(s)
- Yuksel Dogan
- Department of Cardiology, Bakirkoy Dr. Sadi Konuk Education and Research Hospital, Istanbul, Turkey.
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Sideri G, Kafetzis DA, Vouloumanou EK, Papadatos JH, Papadimitriou M, Falagas ME. Ciprofloxacin in critically ill children. Anaesth Intensive Care 2011; 39:635-9. [PMID: 21823382 DOI: 10.1177/0310057x1103900416] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
Data regarding the use of fluoroquinolones in critically ill children are scarce. We present our experience regarding the use of ciprofloxacin in this specific patient population. We prospectively identified all paediatric patients who received ciprofloxacin treatment in the intensive care unit of the tertiary care P. & A. Kyriakou Children's Hospital during a three year period (2005 to 2008). Eighteen paediatric patients (mean age 23 months, 12 females) who received intravenous ciprofloxacin were identified. Various underlying diseases, including malignancy and immunodeficiency, were observed. None of the evaluated patients had cystic fibrosis. Fourteen patients had bacteraemia (mainly caused from Gram-negative pathogens), one had Stenotrophomonas maltophilia pneumonia, while no pathogen was identified in three patients. The latter patients received ciprofloxacin due to the severity of their clinical manifestations. All patients with microbiologically documented infections recovered. Three deaths attributed to the underlying diseases were noted. Within a 10-day follow-up, two cases of diarrhoea, one case of vomiting and one case of reversible supraventricular tachycardia were noted. No case of QT prolongation was noted. The short-term follow-up hampered any assessment of joint and cartilage toxicity, potentially associated with ciprofloxacin treatment. Our study suggests that ciprofloxacin may be a useful option for critically ill children without cystic fibrosis. Even though firm conclusions regarding the safety profile of ciprofloxacin in critically ill children could not be drawn, our study provides useful information regarding short-term adverse events associated with ciprofloxacin.
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Affiliation(s)
- G Sideri
- Pediatric Intensive Care Unit, Department of Microbiology, University of Athens, "P & A. Kyriakou" Children's Hospital and Alfa Institute of Biomedical Sciences, Athens, Greece
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Garazzino S, Tovo PA. Clinical experience with linezolid in infants and children. J Antimicrob Chemother 2011; 66 Suppl 4:iv23-iv41. [PMID: 21521704 DOI: 10.1093/jac/dkr074] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
The worldwide spread of multidrug-resistant organisms has required the development of new antimicrobials. Linezolid, the first oxazolidinone, has a broad spectrum of activity against Gram-positive bacteria, including resistant strains. Although approved by the Food and Drug Administration in 2002, the clinical experience with linezolid in the paediatric population is still limited, also given the fact that in most European countries the paediatric use of linezolid is off-label. In this paper we summarize the actual evidence on both licensed and off-label clinical uses of linezolid in children, including efficacy, safety and tolerability issues. Taking into account the potential bias in comparing heterogeneous clinical trials and reports, the available literature data suggest that linezolid is a safe and effective agent for the treatment of serious Gram-positive bacterial infections in neonates and children. At present, linezolid is reserved for those children who are intolerant to or fail conventional agents. A linezolid-containing regimen can be a valuable option for treating multidrug-resistant and extensively drug-resistant tuberculosis in children as well as disseminated non-tuberculous mycobacterial infections. Given the rare occurrence of serious side effects, careful monitoring of haematological parameters, possible drug interactions and neurological manifestations is recommended in linezolid-treated children, especially in case of prolonged treatments. Appropriate linezolid dosage and hospital infection control measures are essential to avoid the spread of linezolid resistance. Further studies are needed to establish novel paediatric indications for linezolid use and to assess the tolerability of long-term treatments.
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Affiliation(s)
- Silvia Garazzino
- Department of Paediatrics, University of Turin, Regina Margherita Children's Hospital, Infectious Diseases Unit, Piazza Polonia 94, Turin, Italy
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Almpanis G, Siahos S, Karogiannis NC, Mazarakis A, Niarchos C, Kounis GN, Kounis NG. Kounis syndrome: Two extraordinary cases. Int J Cardiol 2011; 147:e35-8. [DOI: 10.1016/j.ijcard.2009.01.031] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2009] [Accepted: 01/15/2009] [Indexed: 02/07/2023]
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Salinas Arce J, Romero R, Solorzano P. A case of prolonged QT interval and torsades de pointes due to ciprofloxacin. Rev Esp Cardiol 2010; 63:111-2. [PMID: 20089234 DOI: 10.1016/s1885-5857(10)70017-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Current awareness: Pharmacoepidemiology and drug safety. Pharmacoepidemiol Drug Saf 2008. [DOI: 10.1002/pds.1490] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
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