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Physiological Research Dec 2022Amiodarone seems to exhibit some antiviral activity in the disease caused by SARS-CoV-2. Here we have examined the SARS-CoV-2 disease course in the entire population of...
Amiodarone seems to exhibit some antiviral activity in the disease caused by SARS-CoV-2. Here we have examined the SARS-CoV-2 disease course in the entire population of the Czech Republic and compared it with the course of the disease in patients treated with amiodarone in two major Prague's hospitals. In the whole population of the Czech Republic SARS-CoV-2 infected 1665070 persons (15.6 %) out of 10694000 (100 %) between 1 April 2020 and 30 June 2021. In the same time period only 35 patients (3.4 %) treated with amiodarone were infected with SARS-CoV-2 virus out of 1032 patients (100 %) who received amiodarone. It appears that amiodarone can prevent SARS-CoV-2 virus infection by multiple mechanisms. In in-vitro experiments it exhibits SARS-CoV-2 virus replication inhibitions. Due to its anti-inflammatory and antioxidant properties, it may have beneficial effect on the complications caused by SARS-CoV-2 as well. Additionally, inorganic iodine released from amiodarone can be converted to hypoiodite (IO-), which has antiviral and antibacterial activity, and thus can affect the life cycle of the virus.
Topics: Humans; COVID-19; Antiviral Agents; SARS-CoV-2; Amiodarone; Anti-Bacterial Agents
PubMed: 36426888
DOI: 10.33549/physiolres.934974 -
The American Journal of Cardiology Nov 1993Concerns about proarrhythmia risk and inefficacy associated with class I antiarrhythmic drugs have revived interest in low-dose amiodarone (maintenance dose 200-400... (Review)
Review
Concerns about proarrhythmia risk and inefficacy associated with class I antiarrhythmic drugs have revived interest in low-dose amiodarone (maintenance dose 200-400 mg/day) for suppression of atrial fibrillation. In nonrandomized trials of amiodarone for atrial fibrillation refractory to conventional agents, amiodarone has been successful in maintaining sinus rhythm in 53-79% of patients during a mean follow-up of 15-27 months. Intolerable side effects, including pulmonary toxicity, are in the range of 1-12% per year and resolve following amiodarone withdrawal in the majority of cases. Proarrhythmia risk associated with amiodarone, even in the setting of left ventricular dysfunction, is extremely low. In patients with congestive heart failure, in whom other pharmacologic options are limited by proarrhythmia risk and negative inotropism, preliminary experience with amiodarone is especially promising. Randomized trials are needed, directly comparing amiodarone to conventional antiarrhythmic therapy for atrial fibrillation suppression and comparing amiodarone to warfarin for thromboembolism prevention in patients with atrial fibrillation refractory to conventional antiarrhythmic drugs.
Topics: Amiodarone; Atrial Fibrillation; Humans
PubMed: 8237834
DOI: 10.1016/0002-9149(93)90967-h -
The Consultant Pharmacist : the Journal... Sep 2010To review the safety and efficacy of the newly approved, mixed-activity antiarrhythmic dronedarone (classes I-IV) versus its parent compound comparator, amiodarone... (Review)
Review
OBJECTIVE
To review the safety and efficacy of the newly approved, mixed-activity antiarrhythmic dronedarone (classes I-IV) versus its parent compound comparator, amiodarone (class III, with mixed activity).
DATA SOURCES
A MEDLINE/PUBMED (January 1966 to March 2010) and International Pharmaceutical Abstract (January 1975 to March 2010) search of English language papers in addition to a bibliographic search of retrieved papers.
STUDY SELECTION
All human studies of dronedarone, alone or in combination with amiodarone, were reviewed.
DATA SYNTHESIS
Approved in July 2009, dronedarone is a new antiarrhythmic agent indicated to reduce the risk of hospitalization for cardiac events in patients with paroxysmal or persistent atrial fibrillation or atrial flutter. Dronedarone has been viewed as a potential therapeutic alternative for amiodarone because of a lower risk for pulmonary, thyroid, and dermatologic adverse effects. Compared with amiodarone, dronedarone has poor bioavailability and a shorter terminal disposition half-life, which dictates a twice-daily dosing regimen. Furthermore, dronedarone failed to demonstrate superiority over amiodarone with respect to recurrence of atrial fibrillation in a comparative efficacy analysis. Dronedarone therapy is more costly and increases overall tablet burden. No dosage adjustments are required with dronedarone for renal impairment. Use of dronedarone is contraindicated in the presence of severe hepatic impairment. No serious organ-related toxicities (i.e., thyroid and pulmonary system) have been reported with use of dronedarone.
CONCLUSION
Dronedarone as a niche drug may be a reasonable theoretical alternative for patients who cannot tolerate amiodarone or have underlying comorbidities that contraindicate amiodarone use (e.g., pulmonary, thyroid disease). However, dronedarone has not been studied in the vast majority of indications and patient populations in which amiodarone has been studied.
Topics: Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Atrial Flutter; Clinical Trials as Topic; Dronedarone; Drug Interactions; Humans
PubMed: 20876046
DOI: 10.4140/TCP.n.2010.555 -
Clinical Pharmacy 1983The chemistry, pharmacology, pharmacokinetics, clinical use and efficacy, adverse effects, and dosage of amiodarone, an investigational antiarrhythmic agent, are... (Review)
Review
The chemistry, pharmacology, pharmacokinetics, clinical use and efficacy, adverse effects, and dosage of amiodarone, an investigational antiarrhythmic agent, are reviewed. Amiodarone hydrochloride (L3428, Cordarone; Labaz Laboratories) is a benzofuran derivative and contains iodine. Amiodarone is a noncompetitive antagonist of alpha- and beta-adrenergic receptors. It is a type III antiarrhythmic agent and causes prolongation of the action potential of atrial and ventricular tissue. The drug is incompletely and variably absorbed following oral administration; bioavailability ranges from 22 to 86%. Peak serum concentrations occur 2-10 hours after an oral dose. Amiodarone has a large volume of distribution and is widely distributed in body tissues. It is metabolized by the liver; half-life following a single dose is 5-20 hours, but terminal half-lives of 14-58 days have been found following discontinuation of long-term therapy. Amiodarone has been effective in treating supraventricular tachycardias in patients with Wolff-Parkinson-White syndrome whose arrhythmias are refractory to other drugs. Preliminary data suggest a potential use for amiodarone in treating atrial fibrillation/flutter and bradycardia-tachycardia syndrome. The drug has also been tested in patients with ventricular arrhythmias with promising results. Amiodarone has many side effects, some of them serious. The cardiovascular, pulmonary, neurologic, and hepatic systems may be affected; the drug also has deleterious effects on the eyes, thyroid gland, and skin. The usual oral adult dose of amiodarone hydrochloride is 600 mg daily for seven days followed by maintenance doses of 200-400 mg daily during initial therapy. Intravenous initial doses of amiodarone hydrochloride 5 or 10 mg/kg via a central line have been used; these are often followed by infusions of 10 mg/kg/day for three to five days. Amiodarone is an effective antiarrhythmic agent whose use is limited by numerous and sometimes serious side effects. Until more clinical data are available, its use should be restricted to treatment of serious arrhythmias refractory to other agents.
Topics: Amiodarone; Arrhythmias, Cardiac; Atrial Fibrillation; Benzofurans; Chemical Phenomena; Chemistry; Electrophysiology; Hemodynamics; Humans; Intestinal Absorption; Kinetics; Tachycardia
PubMed: 6349912
DOI: No ID Found -
Clinical Cardiology Jul 1987This article attempts to provide an overview of the present knowledge of the pharmacokinetics of amiodarone and how this relates to the clinical usage of oral... (Review)
Review
This article attempts to provide an overview of the present knowledge of the pharmacokinetics of amiodarone and how this relates to the clinical usage of oral amiodarone. It is apparent that wide gaps still exist in our knowledge of amiodarone's pharmacokinetics in humans and the best fit for the observations following a single oral dose and chronic dosing is that of a three compartment model with body tissues acting as a large reservoir of the drug; hence the very large volume of distribution (greater than 5001). It remains unclear as to exactly when steady state is achieved except that full clinical efficacy for ventricular tachyarrhythmias may take several weeks following high oral dosing (about 15g). The drug's bioavailability is modest (approximately 40%) and excretion is minimal via the hepatic route. It is extensively metabolised in all tissues to desethylamiodarone, whose antiarrhythmic properties remain to be elucidated. This metabolite is found to parallel amiodarone's concentration in serum but its concentration is variable in tissues. The liver shows the highest, and body fat the lowest concentrations of desethylamiodarone. The minimal effective serum concentration has not been established with certainty, and the unique pharmacokinetics of this agent has made it difficult to perform dose-response studies, especially in life threatening arrhythmias. Similarly, the toxic serum concentrations have not been established though it appears that a higher incidence of side effects occurs if serum concentrations exceed 2.5 mg/l during chronic (steady state) therapy.
Topics: Amiodarone; Dose-Response Relationship, Drug; Humans; Tissue Distribution
PubMed: 3078155
DOI: No ID Found -
American Heart Journal Oct 1983Although synthesized as a coronary dilator for use as an antianginal agent over 20 years ago, amiodarone hydrochloride has recently drawn much attention as a potent... (Review)
Review
Although synthesized as a coronary dilator for use as an antianginal agent over 20 years ago, amiodarone hydrochloride has recently drawn much attention as a potent antiarrhythmic compound for the control of a variety of cardiac dysrhythmias. The rapidly expanding clinical and experimental data continue to emphasize the unusual electrophysiologic, pharmacologic, and especially pharmacokinetic properties of this benzofuran derivative. The compound is a potent coronary dilator and has minimal negative inotropic propensity of a direct nature while exhibiting a mild degree of noncompetitive sympathetic antagonism. Pharmacokinetically, it has a long elimination half-life with a correspondingly long and variable latency of onset of therapeutic effect. Electrophysiologically, the drug has the propensity to lengthen the action potential duration and hence the voltage-dependent effective refractory period in all cardiac tissues after long-term, rather than short-term, administration. It has little effect on depolarization, conduction velocity, or the slow response. The precise ionic mechanisms mediating its effects on repolarization are not known. Clinically, the electrophysiologic effects of the drug differ significantly when it is given by mouth over a longer period and when it is given intravenously, a difference that remains to be explained in terms of mechanism. These differences, however, account for the varying spectrum of the drug's action after single intravenous doses (when its antiarrhythmic effects are essentially explained by the drug's action on the atrioventricular node and possibly its antiadrenergic actions) in comparison to long-term oral administration, which predictably suppresses ectopic activity and lengthens the effective refractory period in all cardiac tissues. These features may account for the drug's remarkable efficacy in the control of supraventricular and ventricular tachyarrhythmias. The safe and rational therapeutic uses of amiodarone as an antiarrhythmic agent presuppose detailed understanding of its manifold pharmacodynamic and pharmacokinetic properties.
Topics: Action Potentials; Amiodarone; Angina Pectoris; Animals; Arrhythmias, Cardiac; Benzofurans; Electrophysiology; Heart; Heart Conduction System; Hemodynamics; Humans; Kinetics; Thyroid Hormones; Triiodothyronine; Vasodilation
PubMed: 6351575
DOI: 10.1016/0002-8703(83)90002-9 -
Nature Reviews. Endocrinology Jan 2010Amiodarone is a benzofuran derivative approved for the treatment of cardiac arrhythmias. Traditionally classified as a class III antiarrhythmic agent, amiodarone... (Review)
Review
Amiodarone is a benzofuran derivative approved for the treatment of cardiac arrhythmias. Traditionally classified as a class III antiarrhythmic agent, amiodarone possesses electrophysiologic properties of all four Vaughan-Williams classes. This drug, however, has high iodine content, and this feature plus the intrinsic effects on the body make amiodarone especially toxic to the thyroid gland. Treatment can result in a range of effects from mild derangements in thyroid function to overt hypothyroidism or thyrotoxicosis. The diagnosis and treatment of amiodarone-induced hypothyroidism is usually straightforward, whereas that of amiodarone-induced thyrotoxicosis and the ability to distinguish between the type 1 and type 2 forms of the disease are much more challenging. Dronedarone was approved in 2009 for the treatment of patients with atrial fibrillation. As amiodarone, dronedarone is a benzofuran derivative with similar electrophysiologic properties. In contrast to amiodarone, however, dronedarone is structurally devoid of iodine and has a notably shorter half-life. In studies reported before FDA approval, dronedarone proved to be associated with significantly fewer adverse effects than amiodarone, making it a more attractive choice for patients with atrial fibrillation or flutter, who are at risk of developing amiodarone-induced thyroid dysfunction.
Topics: Amiodarone; Animals; Anti-Arrhythmia Agents; Dronedarone; Humans; Hypothyroidism; Iodine; Thyroid Diseases; Thyroid Gland; Thyrotoxicosis
PubMed: 19935743
DOI: 10.1038/nrendo.2009.225 -
Pharmacotherapy 1998To review the historical development of amiodarone and the changing perceptions of the drug, and discuss its electrophysiologic, pharmacologic, and pharmacokinetic... (Review)
Review
OBJECTIVES
To review the historical development of amiodarone and the changing perceptions of the drug, and discuss its electrophysiologic, pharmacologic, and pharmacokinetic properties.
METHODS
Review of relevant literature.
RESULTS
In the 1970s and 1980s a plethora of new antiarrhythmic agents, including amiodarone, was introduced. Amiodarone is predominately a class III antiarrhythmic, but also possesses class I, II, and IV effects. By 1977 it was described as the ideal antiarrhythmic agent. However, clinicians underestimated potential difficulties caused by misunderstanding its variable absorption, slow initial response at nonloading dosages, and extended half-life. Elevated dosages also produced frequent adverse effects. Thus, early enthusiasm for the drug's efficacy was gradually replaced by a focus on its toxicity. The 1990s witnessed reacceptance of the agent as more logical initial regimens and lower maintenance dosages decreased adverse effects, and amiodarone emerged as one of the few drugs effective in suppressing and preventing arrhythmias that does not increase mortality. Remaining challenges include delineation of an optimal oral regimen, identification of markers useful in clinical monitoring, and elucidation of the relationship between dose-tissue concentration and response and dose-toxicity associations.
CONCLUSION
Amiodarone is an increasingly valuable component of today's antiarrhythmic therapy.
Topics: Administration, Oral; Amiodarone; Anti-Arrhythmia Agents; Drug Therapy; Humans
PubMed: 9855344
DOI: No ID Found -
Clinics in Chest Medicine Mar 1990Amiodarone pulmonary toxicity is one of the most important examples of drug-induced lung disease by non-cancer chemotherapeutic agents. Current concepts suggest that... (Review)
Review
Amiodarone pulmonary toxicity is one of the most important examples of drug-induced lung disease by non-cancer chemotherapeutic agents. Current concepts suggest that patients may clinically present with an acute illness suggestive of a hypersensitivity picture or with a more chronic indolent course mimicking a malignant process. Likewise, the mechanism of amiodarone pulmonary toxicity suggests that at least two different pathways of toxicity exist: (1) an indirect mechanism characterized by influx of inflammatory or immune effector cells to the lung and (2) a direct toxic mechanism that results in lung parenchymal cell injury and a subsequent fibrotic response. Clearly, there is the potential for much crossover and interaction between the proposed pathways of toxicity in any given patient. A better understanding of the mechanism of amiodarone pulmonary toxicity will not only improve our diagnostic approaches to patients with this serious lung disorder, but will also provide the opportunity to develop unique therapeutic strategies that control the toxicity and potentially not interfere with the intended therapeutic efficacy of the drug.
Topics: Amiodarone; Humans; Lung; Lung Diseases; Phospholipids
PubMed: 2182274
DOI: No ID Found -
JAMA Mar 1990Amiodarone hydrochloride, an iodine-rich drug used in the treatment of tachyarrhythmias, is responsible for the development of thyrotoxicosis in approximately 10% of...
Amiodarone hydrochloride, an iodine-rich drug used in the treatment of tachyarrhythmias, is responsible for the development of thyrotoxicosis in approximately 10% of patients who reside in areas of moderate iodine deficiency. Treatment of amiodarone-induced thyrotoxicosis is difficult since the drug has a prolonged half-life, cardiac decompensation due to underlying heart disease occurs often, and discontinuation of amiodarone therapy may not be possible. We report a patient with severe thyrotoxicosis who received amiodarone for 34 months. Prolonged treatment with methimazole, potassium perchlorate, iopanoic acid, and dexamethasone was unsuccessful in controlling the hyperthyroid state. A near-total thyroidectomy resulted in rapid amelioration of thyrotoxicosis. Since surgery results in rapid control of thyrotoxicosis and permits continued therapy with amiodarone, we suggest that near-total thyroidectomy warrants consideration as definitive treatment for resistant amiodarone-induced thyrotoxicosis.
Topics: Amiodarone; Humans; Male; Middle Aged; Thyroid Function Tests; Thyroidectomy; Thyrotoxicosis
PubMed: 2308184
DOI: No ID Found