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Frontiers in Cellular and Infection... 2022Chagas disease (CD), a neglected tropical disease caused by the protozoan parasite , is an important public health problem mainly in Latin America, leading to...
Chagas disease (CD), a neglected tropical disease caused by the protozoan parasite , is an important public health problem mainly in Latin America, leading to approximately 12,000 annual deaths. Current etiological treatment for CD is limited to two nitro compounds, benznidazole (Bz) and nifurtimox (Nif), both presenting relevant limitations. Different approaches have been employed to establish more effective and safer schemes to treat infection, mostly based on drug repurposing and combination therapies. Amiodarone (AMD), an antiarrhythmic medicament of choice for patients with the chronic cardiac form of CD, is also recognized as a trypanocidal agent. Therefore, our aim is to investigate the combined treatment Bz + AMD on trypomastigote viability, control of intracellular form proliferation, and recovery of the infection-induced cytoskeleton alterations in cardiac cells. The combination of Bz + AMD did not improve the direct trypanocidal effect of AMD on the infective blood trypomastigote and replicative intracellular forms of the parasite. Otherwise, the treatment of -infected cardiac cells with Bz plus AMD attenuated the infection-triggered cytoskeleton damage of host cells and the cytotoxic effects of AMD. Thus, the combined treatment Bz + AMD may favor parasite control and hamper tissue damage.
Topics: Amiodarone; Chagas Disease; Cytoskeleton; Humans; Nitroimidazoles; Trypanocidal Agents; Trypanosoma cruzi
PubMed: 36093188
DOI: 10.3389/fcimb.2022.975931 -
Microbiology Spectrum Feb 2022Chagas disease (CD), caused by Trypanosoma cruzi, affects approximately 6 to 7 million people in Latin America, with cardiomyopathy being the clinical manifestation most...
Chagas disease (CD), caused by Trypanosoma cruzi, affects approximately 6 to 7 million people in Latin America, with cardiomyopathy being the clinical manifestation most commonly associated with patient death during the acute phase. The etiological treatment of CD is restricted to benznidazole (Bz) and nifurtimox (Nif), which involve long periods of administration, frequent side effects, and low efficacy in the chronic phase. Thus, combined therapies emerge as an important tool in the treatment of CD, allowing the reduction of Bz dose and treatment duration. In this sense, amiodarone (AMD), the most efficient antiarrhythmic drug currently available and prescribed to CD patients, is a potential candidate for combined treatment due to its known trypanocidal activity. However, the efficacy of AMD during the acute phase of CD and its interaction with Bz or Nif are still unknown. In the present study, using a well-established murine model of the acute phase of CD, we observed that the Bz/AMD combination was more effective in reducing the peak parasitemia than both monotherapy treatments. Additionally, the Bz/AMD combination reduced (i) interleukin-6 (IL-6) levels in cardiac tissue, (ii) P-wave duration, and (iii) frequency of arrhythmia in infected animals and (iv) restored gap junction integrity in cardiac tissue. Therefore, our study validates AMD as a promising candidate for combined therapy with Bz, reinforcing the strategy of combined therapy for CD. Chagas disease affects approximately 6 to 7 million people worldwide, with cardiomyopathy being the clinical manifestation that most commonly leads to patient death. The etiological treatment of Chagas disease is limited to drugs (benznidazole and nifurtimox) with relatively high toxicity and therapeutic failures. In this sense, amiodarone, the most effective currently available antiarrhythmic drug prescribed to patients with Chagas disease, is a potential candidate for combined treatment due to its known trypanocidal effect. In the present study, we show that combined treatment with benznidazole and amiodarone improves the trypanocidal effect and reduces cardiac damage in acutely T. cruzi-infected mice.
Topics: Amiodarone; Animals; Chagas Disease; Disease Models, Animal; Drug Therapy, Combination; Heart; Heart Diseases; Heart Function Tests; Humans; Male; Mice; Nitroimidazoles; Parasitemia; Trypanosoma cruzi
PubMed: 35138142
DOI: 10.1128/spectrum.01852-21 -
JACC. Clinical Electrophysiology Aug 2022
Topics: Amiodarone; Arrhythmias, Cardiac; Drug-Related Side Effects and Adverse Reactions; Humans
PubMed: 35981795
DOI: 10.1016/j.jacep.2022.05.019 -
American Family Physician Dec 2003Amiodarone is a potent antiarrhythmic agent that is used to treat ventricular arrhythmias and atrial fibrillation. The drug prevents the recurrence of life-threatening... (Review)
Review
Amiodarone is a potent antiarrhythmic agent that is used to treat ventricular arrhythmias and atrial fibrillation. The drug prevents the recurrence of life-threatening ventricular arrhythmias and produces a modest reduction of sudden deaths in high-risk patients. Amiodarone is more effective than sotalol or propafenone in preventing recurrent atrial fibrillation in patients for whom a rhythm-control strategy is chosen. When long-term amiodarone therapy is used, potential drug toxicity and interactions must be considered. The dosage of amiodarone should be kept at the lowest effective level. In patients who also are taking digoxin and warfarin, physicians must pay close attention to digoxin levels and prothrombin time, keeping in mind that the effects of interaction with amiodarone do not peak until seven weeks after the initiation of concomitant therapy. Laboratory studies to assess liver and thyroid function should be performed at least every six months.
Topics: Amiodarone; Anti-Arrhythmia Agents; Drug Interactions; Humans
PubMed: 14677664
DOI: No ID Found -
Journal of the American College of... Oct 2014
Topics: Amiodarone; Anticoagulants; Atrial Fibrillation; Female; Humans; Male
PubMed: 25301456
DOI: 10.1016/j.jacc.2014.07.966 -
Deutsches Arzteblatt International Oct 2018
Topics: Aged, 80 and over; Amiodarone; Anti-Bacterial Agents; Atrial Fibrillation; Dyspnea; Female; Glucocorticoids; Humans; Methylprednisolone; Pneumonia; Radiography; Tomography, X-Ray Computed
PubMed: 30479258
DOI: 10.3238/arztebl.2018.0714b -
Journal of the American College of... May 1986Oral amiodarone therapy was given to seven patients already taking oral flecainide regularly. In one additional patient, administration of flecainide was temporarily...
Oral amiodarone therapy was given to seven patients already taking oral flecainide regularly. In one additional patient, administration of flecainide was temporarily discontinued when amiodarone therapy was begun, and then resumed. Amiodarone produced a rise in mean dose-adjusted flecainide plasma level (trough plasma level at steady state/daily dose) from 2.3 +/- 0.8 to 3.4 +/- 0.9 (ng/ml)(mg/day) (p less than 0.01). Accordingly, the mean dose of flecainide required to maintain similar plasma levels of the drug was one-third lower during combined treatment than during therapy with flecainide alone. This drug interaction must be accounted for when amiodarone and flecainide are used concomitantly.
Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Drug Interactions; Female; Flecainide; Humans; Male; Middle Aged; Piperidines
PubMed: 3958371
DOI: 10.1016/s0735-1097(86)80234-0 -
Clinical Cardiology Mar 1984Amiodarone is an effective antiarrhythmic drug which has been used successfully to treat a variety of cardiac arrhythmias. Early reports emphasized both the striking... (Review)
Review
Amiodarone is an effective antiarrhythmic drug which has been used successfully to treat a variety of cardiac arrhythmias. Early reports emphasized both the striking efficacy of this agent and the relative paucity of side effects necessitating discontinuing treatment with this drug. As amiodarone has been used more widely and in more diverse patient populations, reports of serious thyroid, pulmonary, cardiovascular, and other adverse reactions have appeared in the literature. In this paper, we review the serious adverse effects that have been reported to date. The incidence of these reactions varies considerably in different series, and cannot be explained solely by different doses employed or by varying methods of drug administration. The final role of amiodarone in the therapy of cardiac arrhythmias cannot be determined until the long-term toxicity has been more thoroughly investigated.
Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Heart; Heart Conduction System; Humans; Hyperthyroidism; Infusions, Parenteral; Lung; Thyroid Gland
PubMed: 6368073
DOI: 10.1002/clc.4960070302 -
Journal of the American College of... May 1987Because the value of monitoring amiodarone plasma concentrations remains undefined, this study was performed to evaluate its role during the management of patients...
Because the value of monitoring amiodarone plasma concentrations remains undefined, this study was performed to evaluate its role during the management of patients receiving amiodarone. The early electrophysiologic effects of amiodarone were assessed in 40 consecutive patients with coronary artery disease and sustained ventricular tachycardia or fibrillation who underwent electrophysiologic studies and measurement of amiodarone plasma concentration before and 29 +/- 15 (mean +/- SD) days after initiation of therapy. Amiodarone and desethylamiodarone plasma levels did not correlate with changes in either sinus cycle length, QTc interval, ventricular effective refractory period, AH and HV intervals or ventricular tachycardia cycle length. Amiodarone and desethylamiodarone plasma concentrations and the effects of the drug on conduction intervals or right ventricular effective refractory periods were not related to suppression of arrhythmia induction by ventricular stimulation after 1 month of therapy. The relation between amiodarone plasma concentrations and both toxicity and efficacy during long-term therapy were prospectively assessed in a larger series of 114 consecutive patients with either symptomatic supraventricular or ventricular arrhythmias who were followed up on long-term amiodarone therapy for 26 +/- 15 months. Sixty-three patients (55%) had one or more adverse effects attributed to amiodarone. By life-table analysis, 40, 69 and 80% of patients had experienced an adverse reaction after 1, 2 and 3 years of therapy, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Aged; Amiodarone; Arrhythmias, Cardiac; Coronary Disease; Dose-Response Relationship, Drug; Electrocardiography; Electrophoresis; Female; Humans; Male; Middle Aged; Osmolar Concentration; Recurrence
PubMed: 3571754
DOI: 10.1016/s0735-1097(87)80320-0 -
European Review For Medical and... Dec 2018The aim of the study was to examine the safety and efficacy of dronedarone in patients with a history of atrial fibrillation and amiodarone-induced hyperthyroidism.
OBJECTIVE
The aim of the study was to examine the safety and efficacy of dronedarone in patients with a history of atrial fibrillation and amiodarone-induced hyperthyroidism.
PATIENTS AND METHODS
We conducted a prospective study to evaluate the use of amiodarone and dronedarone in 124 patients with a history of paroxysmal atrial fibrillation who had no additional structural heart disease. All patients received amiodarone 200 mg qd. Out of 124 patients, 56 (45%) switched to dronedarone 400 mg bid due to amiodarone-induced hyperthyroidism and the remaining 68 patients (55%), with normal thyroid function, continued to receive amiodarone. The follow-up period was 12 months, and the patients were regularly monitored.
RESULTS
The primary outcome after 6 months dronedarone and amiodarone group was 56 and 68, including 38 (68%) and 54 (79.4%) (Odds ratio [OR] = 1.17, 95% confidence interval [95% CI] = 0.68-2.02) patients with sinus rhythm (SR) and 18 (32.14%) and 14 (28.6%) (odds ratio [OR] = 0.64, confidence interval [95% CI] = 0.29-1.40) patients with atrial fibrillation (AF). The secondary outcome after 12 months showed significant difference in thyroid function in the dronedarone group. Out of 46 patients, 24 (56.18%) patients reduced hyperthyroidism compared to the amiodarone group; out of 68, 6 (8.9%) patients were observed to have hyperthyroidism. At 12 months, there were 24 (43%) and 22 (62%) (odds ratio [OR] = 0.75, confidence interval [95% CI] = 0.38-1.49) patients with SR, and 32 (57%) and 26 (38%) (odds ratio [OR] = 0.67, confidence interval [95% CI] = 0.36-1.25) patients with AF.
CONCLUSIONS
In our study, dronedarone appears to be a good therapeutic option in the treatment of atrial fibrillation in patients with amiodarone-induced hyperthyroidism. However, long-term studies are needed to estimate the efficacy and toxicity of both drugs.
Topics: Aged; Aged, 80 and over; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Dronedarone; Female; Humans; Hyperthyroidism; Male; Middle Aged; Prospective Studies
PubMed: 30556893
DOI: 10.26355/eurrev_201812_16551