Adverse Effects Of Amiodarone Research Articles

Ventricular Tachycardia and Fibrillation: Amiodarone as a Safety and Prophylactic

Background: The best antiarrhythmic drug on the market right now for treating both atrial and ventricular arrhythmias is amiodarone. This is a derivative of iodinated benzofuran that has shown promise in treating a variety of cardiac arrhythmias, such as life-threatening ventricular arrhythmias, paroxysmal supraventricular tachycardias, and atrial fibrillation. Objective: To assess the status of amiodarone with therapeutic doses in the Bangladeshi population. Materials and Method: The quasi experimental study was conducted in the Department of Cardiology, Northeast Medical College, Sylhet during April, 2022 to March, 2023 patients got admitted in the Department of Cardiology, NMCH, Sylhet, consecutive patients who had been treated with amiodarone for arrhythmia were included in this study. Patients without an amiodarone prescription were assumed and patients who will not give informed written consent were excluded in this study. Result: In multivariable logistic regression, bradycardia or conduction disturbance, amiodarone daily dose (≥300 mg), and duration of amiodarone (>4 month) were substantially (p<0.05) linked with deleterious effects of amiodarone. Conclusion: The most common adverse event was bradycardia or conduction disturbance followed by thyroid toxicity, hepatic toxicity, eye toxicity and pulmonary toxicity. Bradycardia or conduction disturbance, amiodarone daily dose (≥300 mg) and duration of amiodarone (>4 month) was found to be significantly associated with adverse effects of amiodarone.

Safety of Amiodarone in Ventricular Arrhythmia in Patients Admitted in Bangabandhu Sheikh Mujib Medical University

Background: Amiodarone is the most effective antiarrhythmic medications available today for the treatment of both atrial and ventricular arrhythmias. It is an iodinated benzofuran derivative with demonstrated efficacy against a range of cardiac arrhythmias, including atrial fibrillation, paroxysmal supraventricular tachycardias, and life-threatening ventricular arrhythmias. Objective: To evaluation the status of amiodarone with therapeutic dose in Bangladeshi population. Materials and Methods: The quasi experimental study was conducted in the Department of Cardiology in Bangabandhu Sheikh Mujib Medical University (BSMMU), Shahbagh, Dhaka during April, 2019 to March, 2020 Patients got admitted in the Department of Cardiology, BSMMU, consecutive patients who had been treated with amiodarone for arrhythmia were included in this study. Patients without an amiodarone prescription were assumed and patients who will not give informed written consent were excluded in this study. Results: The most common adverse event was bradycardia or conduction disturbance (9.0%) followed by 4(2.2%) thyroid toxicity, 3(1.7%) hepatic toxicity, 2(1.1%) eye toxicity and 1(0.6%) pulmonary toxicity. In multi variable logistic regression, bradycardia or conduction disturbance, amiodarone daily dose (≥300 mg) and duration of amiodarone (>4 month) was found to be significantly (p<0.05) associated with adverse effects of amiodarone. Conclusion: The most common adverse event was bradycardia or conduction disturbance followed by thyroid toxicity, hepatic toxicity, eye toxicity and pulmonary toxicity. Bradycardia or conduction disturbance, amiodarone daily dose (≥300 mg) and duration of amiodarone (>4 month) was found to be significantly associated with adverse effects of amiodarone.
 University Heart Journal Vol. 17, No. 2, Jul 2021; 118-121

Court rules no presumed malice occurred in pharmacy error case

The complexities of tapered dosing can lead to pharmacy liability if the directions given to patients are unclear or incomplete. Exposure to liability may increase when the error is not discovered at the time a prescription is refilled. This type of error was the basis of a lawsuit filed by a patient's estate against the patient's pharmacy, alleging that the patient died due to an amiodarone overdose. The patient was a 71-year-old male with chronic ischemic heart disease and atrial fibrillation. His cardiologist prescribed amiodarone 200-mg tablets. The signatura in the prescription stated: “1 TAB PO UD For Heart Rhythm 400mg 2x/day x 1 week, then 200mg 3x/day x 2 wks, then 200mg 2x/day x 2 wks, then 200mg daily” The pharmacist generated a label that read: “Take 2 tablets by mouth twice daily for 1 week – [800 mg]Then 1 tablet by mouth three times daily for two weeks – [600 mg]Then 1 tablet by mouth twice daily for 2 weeks – [400 mg]”The pharmacist omitted from the label the final part of the instructions to “then take 200 mg daily.” The pharmacist had only 60 tablets in stock, so he dispensed that number of tablets initially. He entered into the computer a quantity of 514 tablets for the prescription. Several days later, a different pharmacist dispensed the remainder of 454 tablets. The second pharmacist did not catch that the patient was to use only one tablet daily after the first 5 weeks. Six months later, a third pharmacist refilled the prescription for 514 tablets, without catching the original error. The patient died, allegedly due to “amiodarone-induced hepatotoxicity.” In the lawsuit that followed, the pharmacy did not contest liability but did move for dismissal of the plaintiff's claim for punitive damages. The court first noted that punitive damages can be awarded to a plaintiff only when there is either actual or presumed malice by the defendant. The plaintiff had not alleged actual malice by the pharmacists, so the court examined the allegation of presumed malice. Prior case law established that presumed malice requires a person to have acted “willfully or wantonly” in causing injury to another person. To prove willful or wanton misconduct, the plaintiff must prove that the defendant “knew or should have known of the substantial probability of serious physical harm and acted with a culpable mental state.” The plaintiff contended that since the pharmacists knew the adverse effects of amiodarone, the error they made was willful and wanton. The court ruled that while the pharmacists were aware of the risk of amiodarone toxicity, “awareness of the risk in and of itself does not constitute presumed malice or willful or wanton misconduct.” The court concluded that “none of the pharmacists—regardless of how irresponsibly neglectful they were or the seemingly dire consequences resulting—had the required culpable mental state by acting in some appreciable nature deliberately or intentionally.” The punitive damage allegations against the pharmacy were dismissed. Although the punitive damages claim has been dismissed, this case will continue based on the allegation of negligence and may result in an award of compensatory damages. Pharmacists can learn several important risk management lessons from the case: □When a complex tapered dose is prescribed, patient counseling can prevent misunderstandings by the patient and can correct errors by the pharmacy.□At the first refilling of prescriptions for a drug that is usually started with a loading dose, it's important to verify the maintenance dose.□Be sure to corroborate a large number of dosage units that would extend beyond a 90-day supply, particularly for a drug that is usually dosed once or twice daily.□To detect and prevent dosing errors, pay special attention to prescriptions for a drug that is labeled with a boxed warning.

The possible therapeutic role of mesenchymal stem cells in amiodarone-induced lung injury in adult male albino rats

Background and aim Lung injury and even pulmonary fibrosis represent a known adverse effect of amiodarone. No effective treatment was reported for pulmonary fibrosis except lung transplantation. Stem cell therapy holds a great promise for the repair of injured tissues. Mesenchymal stem cells (MSCs) have the potential to present a new trend of treatment. This work aimed to study the effect of bone marrow-MSCs on amiodarone-induced lung injury in albino rats by histological methods. Materials and methods Forty-two adult male albino rats were used. Seven rats were used as a source of bone marrow-MSCs. Thirty-five rats were divided into the following groups: negative control group included seven rats that received no treatment; vehicle control group included seven rats that received polysorbate 80; amiodarone group included 14 rats that received daily oral amiodarone for 6 weeks and were subdivided into two equal subgroups as subgroup 3a (amiodarone administrated) and subgroup 3b (kept for 4 weeks after amiodarone stoppage); and stem cell-treated group included seven rats that received stem cells after amiodarone stoppage. Lung specimens were examined histologically. Results Amiodarone group showed disrupted lung architecture, collapsed alveoli, and significant increase in the thickness of interalveolar septa. Bronchioles showed thickened smooth muscle layer and obliterated lumens. Highly significant increase in area percent of collagen fibers was observed. In stem cell group, there was improvement of these histological changes. Conclusion MSCs can improve the deleterious effects associated with amiodarone-induced lung injury.

UNUSUAL PRESENTATION OF AMIODARONE INDUCED PULMONARY TOXICITY

Pulmonary toxicity is a serious adverse effect of amiodarone. 62-year-old male presenting with 7 days duration of acute dyspnea. His past medical history included hypertension and coronary artery disease. He was diagnosed with atrial fibrillation (AF) 2 months before presentation, when he was

The blue child – amiodarone‐induced blue‐gray skin syndrome and pulmonary mass in a child

Adverse effects of amiodarone are rarely seen in pediatric patients, but may occur if amiodarone is applied for long-term treatment. Two rather rare phenomena are blue-gray skin pigmentation and pulmonary mass. They represent important differential diagnoses from more common clinical complications like pneumonia and drug-induced toxic skin lesions.

The incidence and predictors of overall adverse effects caused by low dose amiodarone in real-world clinical practice

Background/AimsMost current knowledge regarding amiodarone toxicity derives from clinical trials. This study was performed to investigate the incidence and risk factors of overall adverse effects of amiodarone in real-world practice using a large sample size.MethodsBetween January 1, 2000 and March 10, 2012, a total of 930 consecutive patients who had been treated with amiodarone for arrhythmia were reviewed retrospectively. An amiodarone-associated adverse event was considered in cases of discontinuation or drug dose reduction due to an unexpected clinical response.ResultsThe mean daily dose of amiodarone was 227 ± 126 mg, and the mean duration was 490 ± 812 days. During the mean follow-up duration of 982 ± 1,137 days, a total of 154 patients (16.6%) experienced adverse effects related to amiodarone, the most common being bradycardia or conduction disturbance (9.5%). Major organ toxicities in the thyroid (2.5%), liver (2.2%), eyes (0.6%), and lungs (0.3%) were rare. All patients recovered fully without complications after amiodarone discontinuation or dose reduction. The only independent predictor of adverse effects was the duration of amiodarone treatment (odds ratio, 1.21; 95% confidence interval, 1.03 to 1.41; p = 0.016, per year).ConclusionsLow-dose amiodarone is well tolerated in a real-world clinical population. Further studies with a prospective design are needed to confirm this finding.

Amiodarone-induced pulmonary toxicity: Case study with syndrome analysis

Amiodarone is often prescribed for the control of atrial and ventricular arrhythmias. While generally effective, the potential for a variety of side effects is substantial. Pulmonary toxicity, leading to acute or chronic respiratory failure, manifests with cough, dyspnea, infiltrates on chest radiograph, and a potential for progression to death. Although routinely cited as an adverse effect of amiodarone, it is relatively rare in terms of statistical incidence. In an effort to shed light on this syndrome, we present a stereotypical case study in amiodarone-induced pulmonary toxicity, as a prelude to a review of theorized pathophysiology, epidemiology, clinical presentation, diagnosis, therapeutics, monitoring recommendations, and areas for future research.

Amiodarone and the thyroid dysfunction

Amiodarone, a class III antiarrhytmic agent, is a benzofuran derivative containing 75 mg iodide per 200 mg tablet. During the metabolism of 200 mg of the drug approximately 6-8 mg of inorganic iodine is released into the systemic circulation. Amiodarone is very lipophilic and concentrates in various tissues and organs such as adipose tissue, skeletal muscles, myocardium, liver, lung and thyroid. Amiodarone is dealkylated in the liver to its major active metabolite desethylamiodarone. Amiodarone therapy is associated with a number of side effects, including thyroid dysfunction – thyrotoxicosis in 2-15% and hypothyroidism in 5-20% of patients, respectively. The effects of amiodarone on thyroid function depend on underlying thyroid status and dietary iodine intake. Patients with autoimmune thyroid disease are more likely to develop hypothyroidism due to failure to escape from Wolff-Chaikoff effect. In patients with multinodular goiter or latent Graves’ disease hyperthyroidism may occur. Amiodarone may also cause destructive thyroiditis in patients without underlying thyroid disease. Thyrotoxicosis may be a result of increased synthesis of thyroid hormones (type 1) or of their excessive release due to a direct damage of thyroid cells caused by amiodarone, its metabolite desethylamiodarone or iodine (type 2). The distinction between type 1 and type 2 thyrotoxicosis is crucial, since therapy is different in these two types. The differential diagnosis is based on the presence of goiter, evaluation of thyroid autoantibodies, colour flow Doppler image, thyroid uptake and on the response to steroids or perchlorate. Patients with type 1 thyrotoxicosis require thionamides or potassium/sodium perchlorate, while those with type 2 – corticosteroids. Hypothyroidism is treated with L-thyroxine. The signs and symptoms of amiodarone-induced thyrotoxicosis and hypothyroidism can be scanty. Therefore, all patients treated with amiodarone need periodic examination of thyroid function. Apart from inducing thyroid dysfunction, amiodarone causes hypercholesterolemia due to decreased expression of the LDL receptor gene, which is regulated by T3. Adverse effects of amiodarone have led to the search for analogues with the same efficacy but safer profile. Dronedarone is structurally related to amiodarone but does not contain iodine atoms and does not increase the incidence of thyroid disease. Dronedarone appears to be less-effective but may be beneficial for patients with atrial fibrillation or flutter who are at risk of developing amiodarone induced thyroid dysfunction.

Recurrent Interstitial Pneumonitis and Pulmonary Hemorrhage Secondary to Amiodarone Toxicity

Introduction Amiodarone is a commonly used drug for the treatment of cardiac arrhythmias. It has a broad range of toxicity including photosensitivity, blue-gray discoloration of the skin, thyroid dysfunction, corneal deposits, abnormal liver function tests, and bone marrow suppression. 1 Pulmonary toxicity is the most serious adverse effect of amiodarone. Treatment of amiodaroneinduced pulmonary toxicity includes discontinuation of the drug and initiation of glucocorticoid therapy in the majority of symptomatic patients. This case of recurrent amiodarone toxicity was manifested by acute interstitial pneumonitis and diffuse alveolar hemorrhage after a rapid taper of glucocorticoids.

Amiodarone for the Emergency Care of Children

Amiodarone is a class 3 antiarrhythmic agent used for a broad range of arrhythmias including adenosine-resistant supraventricular tachycardia, junctional ectopic tachycardia, and ventricular tachycardia. Compared with adults, there are few data on its use in children with arrhythmias resistant to conventional therapy. National and international guidelines for cardiopulmonary resuscitation and emergency cardiovascular care recommend its use for a variety of arrhythmias based on case reports, cohort studies, and extrapolation from adult data. This article will review the historical development, chemical properties, metabolism, indications and contraindications, and adverse effects of amiodarone in infants and children. After completing this CME activity, the reader should be able to utilize amiodarone in the pediatric population for arrhythmias and identify complications associated with its use.

Efficacy and safety of dronedarone: a review of randomized trials

Importance of the field: Dronedarone is developed for treatment of atrial fibrillation (AF) or flutter (AFL). It is a noniodinized amiodarone analogue and believed to be without the adverse effects of amiodarone. However, long-term adverse effects are not yet well investigated.Areas covered in this review: This is a review of seven studies on dronedarone.What the reader will gain: DAFNE established an effective dose to be 400 mg b.i.d. ADONIS and EURIDIS showed significant prevention of AF/AFL recurrence hazard ratio (HR 0.78 and 0.73) compared to placebo. In ATHENA, cardiovascular death/hospitalization was significantly reduced (HR 0.76) in patients with AF and additional risk factors. ANDROMEDA was stopped because dronedarone increased early mortality (HR 2.13) in advanced heart failure (HF). ERATO found that dronedarone significantly reduced heart rate compared to placebo in patients with AF. DIONYSOS showed that amiodarone was superior to dronedarone to maintain sinus rhythm in patients with AF/AFL.Take home message: Dronedarone is superior to placebo but less efficient than amiodarone in maintaining sinus rhythm in patients with a history of AF. In patients with AF and risk factors dronedarone reduces cardiovascular mortality and morbidity, but in patients with severe HF dronedarone significantly increases mortality.

Management of hypertrophic cardiomyopathy in children.

Hypertrophic cardiomyopathy (HCM) is an inherited cardiac disease characterized by unexplained left ventricular hypertrophy, typically involving the interventricular septum. Hypertrophy may be present in infants, but commonly develops during childhood and adolescence. Management of children with HCM aims to provide symptomatic relief and prevention of sudden death, which is the primary cause of death. Unfortunately, no randomized comparative trials to date have assessed different treatment options in HCM. Medical treatment with negative inotropic agents (beta-adrenoceptor antagonists [beta-blockers], verapamil) is the first therapeutic choice in all symptomatic patients. Beta-blockers also appear to have prognostic merit in children. Surgical myectomy is effective in reducing symptoms in children with left ventricular (LV) obstruction who are unresponsive to medical treatment, although a repeat operation may be needed in a substantial proportion of patients due to relapse of LV obstruction. The recently introduced percutaneous septal ablation can also be regarded as a feasible alternative in this cohort. Technical limitations of both invasive therapeutic options should be carefully considered, preferably in experienced centers. Results of recent randomized trials indicate that dual chamber pacing, once considered a therapeutic option for patients with HCM, should only be used as treatment for conduction abnormalities. Regular clinical risk stratification for sudden death is of vital importance for the prevention of sudden death in young patients. Familial history of sudden death at a young age, LV hypertrophy >3 cm, unexplained syncope, nonsustained ventricular tachycardia in Holter monitoring, and abnormal blood pressure response during exercise are currently considered clinical risk factors for sudden death. Each factor has a low positive predictive accuracy, but patients having two or more of these risk factors are deemed as high risk. Secondary prevention of sudden death in patients successfully resuscitated from cardiac arrest and/or sustained ventricular tachycardia warrants treatment with an implantable cardioverter defibrillator (ICD). Primary prevention of sudden death in patients considered to be at high risk should aim at the management of obvious arrhythmogenic mechanisms (paroxysmal atrial fibrillation, sustained monomorphic ventricular tachycardia, conduction system disease, accessory pathway, myocardial ischemia), and the prevention and/or management of ventricular tachyarrhythmias with amiodarone and/or ICD implantation, respectively. The choice of treatment in children is greatly influenced by technical aspects, such as adverse effects of amiodarone, and ICD implantation difficulties or complications. Amiodarone could also be used as a bridge in children at high risk, until they reach adulthood, possibly achieving a lower risk status, or until their physical growth permits ICD implantation as long-term therapy.

The effect of amiodarone and/or antioxidant treatment on splenocyte blast transformation

Previous studies have shown that free radical reactions may play an important role in the pathogenesis of the adverse effects of the antiarrhythmic agent amiodarone. The aim of this study was to investigate the role of free radical reactions in amiodarone-induced changes in the cell-mediated immune response. Therefore, we investigated the effects of amiodarone alone and in combination with either vitamin E or silymarin on (a) spontaneous blast transformation of splenocytes, (b) concanavalin A (con A)-induced proliferation of splenocytes at three different lectin concentrations, and (c) the content of conjugated dienes in liver homogenate. Forty-eight male Fischer 344 rats were randomized to one of the following groups: 1, control; 2, amiodarone; 3, vitamin E; 4, amiodarone+vitamin E; 5, silymarin; 6, amiodarone+silymarin. The con A-induced splenocyte proliferation was significantly decreased in amiodarone-treated rats at all three lectin concentrations. In the amiodarone-treated group, the change of spontaneous blast transformation was not significantly different from the control. In groups treated with amiodarone plus either antioxidant, both the spontaneous and con A-induced splenocyte proliferation were significantly increased compared with the amiodarone-treated group, and were similar to those in the control group. Amiodarone treatment significantly increased, and both silymarin and vitamin E combined with amiodarone significantly decreased, the conjugated diene content of liver homogenate compared with amiodarone treatment alone. In conclusion, free radicals generated by amiodarone may be implicated in the adverse effects of amiodarone on cell-mediated immune response, and antioxidants applied together with amiodarone may protect against or reduce both the unfavorable immunological effects of amiodarone and amiodarone toxicity.

Positive Coombs' test results in two dogs treated with amiodarone.

Effects of amiodarone, an antiarrhythmic drug that is effective in suppressing severe ventricular arrhythmias that are refractory to other antiarrhythmic drugs, were evaluated in 2 dogs with cardiac disease. One dog was a Doberman Pinscher with cardiomyopathy that developed severe thrombocytopenia after receiving amiodarone for 7 months. The second was a Giant Schnauzer with acquired mitral valve degeneration that developed regenerative anemia after receiving amiodarone for 5 months. Results of direct Coombs' tests were positive in both dogs. Adverse effects of amiodarone are numerous; in dogs, the most common adverse effects are anorexia and hepatotoxicosis. Frequent CBC and serum biochemical analyses should be performed when amiodarone is administered with the intent of continuing the drug indefinitely.

Adverse effects of amiodarone.

Amiodarone was introduced 30 years ago as an antianginal agent and subsequently has been used as an antiarrhythmic agent. This drug was initially used for patients with malignant ventricular arrhythmias; however, currently it is being used broadly for rate and rhythm control in patients with atrial fibrillation. At first, amiodarone was primarily used by cardiologists and today it is used throughout the medical profession. Amiodarone therapy can potentially result in a wide range of adverse effects. The majority of these adverse effects are dose related and reversible. The following is a review of the adverse effects and drug interactions of amiodarone along with recommendations for identification and management of these adverse effects.

Effect of amiodarone on 3H-ouabain binding sites in human skeletal muscle

Na,K-ATPase, or the Na,K-pump, is essential for the excitability and contractility of muscle tissue. Hypothyroidism in associated with a marked decrease in the Na,K-pump concentration in skeletal muscle and myocardium. In 7 patients on long-term amiodarone treatment there was a 36% reduction in the concentration of 3H-ouabain binding sites in skeletal muscle biopsies compared to 7 healthy subjects. This decrease during long-term amiodarone treatment may represent an equivalent reduction in the concentration of the functional Na,K-pump and it may be important in the adverse effect of amiodarone on muscle.

An overview of the adverse effects of amiodarone

An overview of the adverse effects of amiodarone

Adverse effects of amiodarone. Pathogenesis, incidence and management.

Amiodarone is an extremely effective antiarrhythmic agent for the treatment of both life-threatening ventricular arrhythmias and refractory supraventricular tachyarrhythmias. Subjective minor side effects are common with amiodarone but rarely require discontinuation of therapy and are often handled by dose reduction. Serious end-organ toxicity, including pulmonary fibrosis and drug-induced hepatitis, have been the most common indications for discontinuing amiodarone therapy in these patients.

Hemodynamic Effects of Amiodarone

The hemodynamic effects of amiodarone vary according to many factors which include the method of administration and each patient's medical conditon and histroy. Adverse effects of amiodarone are serious but can be minimized by appropriate dosage adjustments. At this time, amiodarone does not appear to cause significant deterioration of myocardial function even though there are risks of other serious adverse reactions.