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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 -
Progress in Cardiovascular Nursing 2007
Review
Topics: Amiodarone; Anti-Arrhythmia Agents; Drug Interactions; Drug-Related Side Effects and Adverse Reactions; Humans
PubMed: 17786095
DOI: 10.1111/j.0889-7204.2007.07398.x -
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 -
The Annals of Pharmacotherapy Jun 1996To review the clinical pharmacology, pharmacokinetics, and clinical efficacy and safety of intravenous amiodarone. (Review)
Review
OBJECTIVE
To review the clinical pharmacology, pharmacokinetics, and clinical efficacy and safety of intravenous amiodarone.
DATA IDENTIFICATION
Articles were identified through a computer search of the English-language literature using MEDLINE (KR Information OnDisc) and the search term amiodarone. Additional articles were identified through examination of the bibliographies of the articles initially retrieved.
STUDY SELECTION
Relevant or representative animal studies, clinical trials, and case reports were selected for evaluation. Particular emphasis was placed on studies pertaining to the use of intravenous amiodarone in treatment-refractory ventricular fibrillation (VF) and hemodynamically unstable ventricular tachycardia (VT).
DATA EXTRACTION
The literature was assessed for adequate description of patients, study methodologies (e.g., study design, number of patients), and outcomes.
DATA SYNTHESIS
Amiodarone is an unusual class III antiarrhythmic that produces each of the four main types of antiarrhythmic action in addition to other effects, such as vasodilatory, selective antithyroid, and other activities that may be therapeutically relevant. Amiodarone pharmacokinetics demonstrate extensive interpatient variability and are characterized by wide tissue distribution (steady-state volume of distribution 40-84 L/kg), slow total body clearance (90-158 mL/h/kg), long terminal elimination half-life (20-47 d), and extensive hepatic metabolism. The onset of maximal antiarrhythmic effect is a function of both amiodarone dosage and time. The high plasma concentrations achieved with intravenous dosing do not fully replicate the electrophysiologic effects observed following long-term oral administration, particularly with respect to class III activity. Available data suggest that intravenous amiodarone is associated with an efficacy rate of 50% or more in treatment-refractory VT/VF, and has a relatively rapid (2-24 h) onset of action. The drug is relatively well tolerated, but close hemodynamic, electrocardiographic, and hepatic function monitoring are required. The value of using amiodarone serum concentrations to guide therapy remains uncertain.
CONCLUSIONS
Intravenous amiodarone is an effective, relatively safe antiarrhythmic for the treatment of recurrent, hemodynamically unstable VT/VF refractory to other drug therapy in the acute care setting.
Topics: Amiodarone; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Clinical Trials as Topic; Humans; Injections, Intravenous
PubMed: 8792951
DOI: 10.1177/106002809603000612 -
Drug Intelligence & Clinical Pharmacy Feb 1983Amiodarone, although widely studied in Europe, is a recent addition to the investigational antiarrhythmics being used in the U.S. Pharmacologically, its primary cardiac... (Review)
Review
Amiodarone, although widely studied in Europe, is a recent addition to the investigational antiarrhythmics being used in the U.S. Pharmacologically, its primary cardiac effects are to increase coronary artery blood flow, increase the effective refractory period, and produce an atropine-resistant bradycardia. Amiodarone is incompletely (approximately 50 percent) and slowly (peak serum concentration approximately 6 h) absorbed. With chronic administration, it deposits both in adipose tissue and in organs with high blood perfusion. It has an apparent elimination half-life of 15-45 days, which presents unique dosing problems. The apparent therapeutic range is 0.6-3 microgram/ml. Amiodarone is 85-95 percent effective in the treatment of atrial tachyarrhythmias and 70-80 percent effective in ventricular tachyarrhythmias. It appears to be of particular value in chronic atrial fibrillation/flutter because it may be able to maintain sinus rhythm after cardioversion. Side effects, although uncommon, may prevent the drug from becoming a standard of therapy. Drug interactions, particularly with warfarin and digoxin, as well as pulmonary fibrosis are of concern.
Topics: Amiodarone; Animals; Benzofurans; Humans; Kinetics; Tachycardia; Tissue Distribution
PubMed: 6337802
DOI: 10.1177/106002808301700203 -
British Journal of Clinical Practice.... Apr 1986
Topics: Amiodarone; Benzofurans; Biological Availability; Drug Interactions; Half-Life; Humans; Kinetics; Tissue Distribution
PubMed: 3089248
DOI: No ID Found -
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