Amiodarone structure activity relationship for quinolones

Amiodarone - DrugBank

Azithromycin and levofloxacin have been shown to be efficacious in treating infections. effects on cardiac function, but it can cause early after depolarizations (EADs). .. An analysis of the time-relations of electrocardiograms. QT prolongation associated with azithromycin/amiodarone combination. In studying the structure-activity relationships of the early 4-quinolones, the It featured a cyclopropyl group on position 1 of the quinolone ring structure. III antiarrhythmic agents (quinidine, procainamide, amiodarone, sotalol) (, ). Similar Structures. Structure for Amiodarone (DB) Levofloxacin, The metabolism of Amiodarone can be decreased when combined with Levofloxacin. inducers, inhibitors and structure-activity relationships of human Cytochrome .

Amiodarone is a classical antiarrythmic agent with a long list of adverse effects. This article attempts to review the structure activity relationship of some of the homologues of amiodarone in order to determine the most clinically desirable molecule. Introduction Structural modifications are made in a molecule and compounds are substituted to either improve their pharmacokinetic profile or to enhance their receptor affinity in order to increase pharmacological response.

Insertions of certain functional groups to specific positions in a molecule result in specific outcomes. In order to properly quantify these outcomes in terms of pharmacological behavior, detailed SAR studies are vital in determination of a desired compound with ideal properties.

A Review of Structure Activity Relationship of Amiodarone and Its Derivatives

Amiodarone Amiodarone is an antiarrythmic agent discovered in commonly used for cardiac dysrythmias. Singh and Williams accounted for its anti-anginal properties [2] while the clinical proof of its efficacy in supraventricular and ventrical arrhythmias was given by Rosenbaum et al.

It is currently indicated in ventricular tachycardia, ventricular fibrillation [4] and atrial fibrillation following an open heart surgery [5].

Despite its unmatched efficacy, the use of Amiodarone is associated with a long list of adverse effects, some being fatal such as pulmonary fibrosis. In acute phase, Amiodarone exerts its effects by blocking inward Sodium and Calcium currents suppressing excitability of cardiomyocytes. It also blocks ligand and voltage gated Potassium channels.

In chronic phase, mediated also by its exceptionally long half-lived active metabolite, desethylamiodarone, it causes down-regulation of Kv1.

First, risk factors and concomitant medications should be screened and evaluated before starting treatment [ 65 ]. Albert and Schuller screened patients with COPD by performing an ECG before azithromycin use, documenting the history of heart failure, episodes of hypokalemia, a family history of prolonged QT or use of other medications that is potential to prolong the QT interval, and conducted an ECG before starting the medication therapy [ 5566 ].

This approach was considered as cost-effective by Berg et al. Second, in outpatient setting, patients should be educated on reporting symptoms of dizziness, palpitations or syncope. It seems prudent to perform a baseline ECG and monitor it during the treatment, although the applicability might be another problem. Third, if the QT interval gets over ms, patients should be dutifully monitored until the ECG gets back to normal.

Finally, additional research is needed to clarify the discordant research findings and to identify if the risk is true, and if so, what patients are at highest risk. In the meantime, azithromycin and levofloxacin could be used when needed, but the potential risks must be understood. The warning included a statement that the risks of cardiovascular death associated with azithromycin were similar to levofloxacin.

Sulfonamides Structure Activity Relationship

Concerns about cardiac effects from azithromycin and levofloxacin emerged after two retrospective studies evaluating azithromycin and levofloxacin. However, azithromycin, the most frequently used antibiotic, is reported to be less likely than other macrolides to cause QT prolongation and cardiac arrhythmias. Studies evaluating the cardiovascular risk of azithromycin and levofloxacin are controversial. Decisions regarding the initiation of azithromycin and levofloxacin should be made on a case-by-case basis.

When a patient has an indication for either of these two drugs, clinicians should not be reluctant to prescribe them. If the QT interval gets over ms, patients should be dutifully monitored until the ECG gets back to normal. This box summarizes key points contained in the article.

Footnotes Declaration of interest The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents, received or pending, or royalties.

Authors do not have any conflict of interest pertaining to this review article. The review article was developed and conducted solely by authors.

N Engl J Med. The use of medicines in the United States review of Food and Drug Administration. Sanford guide to antimicrobial therapy. Azithromycin and the risk of cardiovascular death. This is the first observational study that accessed the cardiac risks and raised increased concern of cardiac risks of azithromycin. Azithromycin and levofloxacin use and increased risk of cardiac arrhythmia and death. This is the most recently published study evaluating the cardiac risks of azithromycin and levofloxacin.

FDA Statement regarding azithromycin Zithromax and the risk of cardiovascular death. Use of azithromycin and death from cardiovascular causes. This observational study examined the cardiac risks of azithromycin in patients aged 18 — An analysis of the time-relations of electrocardiograms. Prolonged QTc interval and risk of sudden cardiac death in a population of older adults.

J Am Coll Cardiol. Risk stratification in the long-QT syndrome. Drug-induced prolongation of the QT interval. Long QT syndromes and torsade de pointes. Prevention of torsade de pointes in hospital settings: Female gender as a risk factor for torsades de pointes associated with cardiovascular drugs.

Cardiac risks associated with antibiotics: azithromycin and levofloxacin

Drug-induced QT interval prolongation: Ther Adv Drug Saf. Antimicrobial-associated QT interval prolongation: The cardiotoxicity of macrolides: Randomized secondary prevention trial of azithromycin in patients with coronary artery disease and serological evidence for Chlamydia pneumoniae infection: Effect of short-term treatment with azithromycin on recurrent ischaemic events in patients with acute coronary syndrome in the Azithromycin in Acute Coronary Syndrome AZACS trial: Azithromycin for the secondary prevention of coronary heart disease events: Azithromycin for the secondary prevention of coronary events.

Potentially fatal interaction between azithromycin and disopyramide. Torsade de pointes and cardiorespiratory arrest induced by azithromycin in a patient with congenital long QT syndrome. Med Clin Barc ; 3: Azithromycin-induced QT prolongation in elderly patient. Polymorphic ventricular tachycardia with a normal QT interval following azithromycin. A case of QT-interval prolongation precipitated by azithromycin. Azithromycin-induced torsade de pointes. Azithromycin as a cause of QT-interval prolongation and torsade de pointes in the absence of other known precipitating factors.

J Interv Card Electrophysiol. Drug-induced QT prolongation and sudden death. QT interval prolongation and extreme bradycardia after a single dose of azithromycin. Sudden cardiac arrest in a patient on chronic methadone after the addition of azithromycin.

Am J Med Sci. Strle F, Maraspin V. Is azithromycin treatment associated with prolongation of the Q-Tc interval? Association of azithromycin with mortality and cardiovascular events among older patients hospitalized with pneumonia.

This study examined the cardiac risks and deaths associated with azithromycin among patients who were hospitalized with pneumonia. Levofloxacin induced polymorphic ventricular tachycardia with normal QT interval. Levofloxacin-induced torsades de pointes. Tex Heart Inst J. Fluconazole- and levofloxacin-induced torsades de pointes in an intensive care unit patient. Am J Health Syst Pharm.


QTc prolongation associated with combination therapy of levofloxacin, imipramine, and fluoxetine. Effects of three fluoroquinolones on QT analysis after standard treatment courses. Effects of three fluoroquinolones on QT interval in healthy adults after single doses. Effect of ciprofloxacin and levofloxacin on the QT interval: A randomized trial comparing the cardiac rhythm safety of moxifloxacin vs levofloxacin in elderly patients hospitalized with community-acquired pneumonia.

The cardiovascular safety of azithromycin. Sex hormones prolong the QT interval and downregulate potassium channel expression in the rabbit heart. Cardiac actions of erythromycin: Testosterone diminishes the proarrhythmic effects of dofetilide in normal female rabbits.

Wu Y, Anderson ME. Reduced repolarization reserve in ventricular myocytes from female mice. Sex difference in risk of torsade de pointes with d,l-sotalol. Sex differences in the evolution of the electrocardiographic QT interval with age. Impact of sex and gonadal steroids on prolongation of ventricular repolarization and arrhythmias induced by I K -blocking drugs.

Macrolide antibiotics and the risk of cardiac arrhythmias.