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Polish Archives of Internal Medicine Jun 2022
Topics: Antazoline; Anti-Arrhythmia Agents; Atrial Fibrillation; Humans
PubMed: 35766936
DOI: 10.20452/pamw.16264 -
Pharmaceuticals (Basel, Switzerland) Mar 2022Antazoline is an antihistaminic drug that is effective in the termination of paroxysmal atrial fibrillation. Despite its long presence in the market, antazoline's ADME...
Antazoline is an antihistaminic drug that is effective in the termination of paroxysmal atrial fibrillation. Despite its long presence in the market, antazoline's ADME parameters and pharmacokinetic effects in humans are poorly characterized. The objective of this study was to fill this gap by generation of in vitro and in vivo data and the development of a physiologically based pharmacokinetic model describing antazoline and its main metabolite disposition. A set of ADME parameters for the antazoline and its hydroxy metabolite is provided based on literature data, QSAR predictions, in vitro binding and metabolic stability assays. These can be used to feed PBPK models. In our current work, the developed PBPK model simulating simultaneously the pharmacokinetic profile of antazoline and its metabolite was successfully verified against the available clinical data and the presented capability to account for the clinically observed variability. When used to feed the PD model (e.g., simulating ECG), concentration-time profiles predicted by the model enable the assessment of antazoline's effect in various clinical scenarios with the possibility to account for population differences or CP mediated drug-drug interactions.
PubMed: 35337175
DOI: 10.3390/ph15030379 -
Polskie Archiwum Medycyny Wewnetrznej Jun 2016INTRODUCTION Numerous studies described the effectiveness and safety of antazoline in pharmacological cardioversion of short‑duration atrial fibrillation (AF).... (Comparative Study)
Comparative Study
Comparative effectiveness and safety of antazoline‑based and propafenone‑based strategies for pharmacological cardioversion of short‑duration atrial fibrillation in the emergency department.
INTRODUCTION Numerous studies described the effectiveness and safety of antazoline in pharmacological cardioversion of short‑duration atrial fibrillation (AF). However, there are no data on the comparison of antazoline and antiarrhythmic drugs listed in clinical guidelines. OBJECTIVES The aim of the study was to assess the comparative effectiveness and safety of antazoline‑based and propafenone‑based strategies in pharmacological cardioversion of short‑duration AF performed in our emergency department. PATIENTS AND METHODS We conducted a retrospective case‑control study based on the analysis of medical records of patients undergoing pharmacological cardioversion of short‑duration AF with intravenous antazoline or propafenone at our department in the years 2008-2012. The primary endpoint was the successful cardioversion of AF. The primary safety endpoint was hospitalization due to the adverse effects of the treatment. RESULTS We analyzed 432 cases of cardioversion. The mean age of patients was 68.9 ±9.8 years; 65% of the patients were male; 90% of the patients had a history of AF. Antazoline was administered 334 times and propafenone-98 times. The mean dose of antazoline was 172 ±65 mg, while all patients in the propafenone group received the drug at a fixed dose of 70 mg (1 vial). Cardioversion with antazoline was successful in 239 cases (71.6%) and with propafenone-in 54 patients (55.1%) (relative risk [RR], 1.30; 95% confidence interval [CI], 1.07-1.57). The rate of hospitalization due to the adverse effects of the treatment were low and similar between the study groups: 10 (3.0%) for antazoline and 4 (4.1%) for propafenone (RR, 0.73; 95% CI, 0.23-2.27). CONCLUSIONS The antazoline‑based strategy was more effective and safer in comparison with propafenone‑based strategy in the pharmacological cardioversion of short‑duration AF in our emergency department.
Topics: Aged; Aged, 80 and over; Antazoline; Anti-Arrhythmia Agents; Atrial Fibrillation; Emergency Service, Hospital; Female; Humans; Male; Middle Aged; Patient Safety; Propafenone; Retrospective Studies; Treatment Outcome
PubMed: 27362390
DOI: 10.20452/pamw.3452 -
Polish Archives of Internal Medicine Sep 2023The choice between rhythm and rate control strategy represents one of the most intriguing dilemmas in the management of atrial fibrillation (AF). Although the advantage... (Review)
Review
The choice between rhythm and rate control strategy represents one of the most intriguing dilemmas in the management of atrial fibrillation (AF). Although the advantage of rhythm over rate control in terms of outcome has not been unequivocally proven, the initial management of patients with symptomatic episodes of AF frequently involves early cardioversion. As electrical cardioversion (EC) is challenging in terms of fasting status and involvement of an anesthesiologic team, pharmacological cardioversion (PC) is usually selected as the first step toward rhythm conversion. Qualification criteria for PC or EC are similar and should comprise assessment of hemodynamic status, estimation of arrhythmic episode duration, evaluation of anticoagulation regimen, exclusion of other supraventricular arrhythmias, and assessment of the chance of rhythm conversion and persistence of sinus rhythm. Finally, the choice of adequate antiarrhythmic drug (AAD) depends on the presence of structural heart disease (SHD) and local experience. In patients without any SHD, complications occur rarely, hence traditional (propafenone, flecainide) or nonclassical Vaughan-Williams class I (antazoline) or class III (vernakalant, ibutilide, or dofetilide) drugs are preferred. The presence of SHD consistent with any left ventricular hypertrophy, heart failure, myocardial ischemia, or valvular heart disease limits the choice of AAD to amiodarone. Given the risk of ventricular proarrhythmia of AAD, safety should always prevail over the enticing possibility of rhythm conversion. The present review aims to provide a comprehensible summary of proper qualification for PC, selection of suitable AAD, and state‑of‑the‑art periprocedural management of patients with recent‑onset AF.
Topics: Humans; Atrial Fibrillation; Electric Countershock; Anti-Arrhythmia Agents; Propafenone; Heart Failure; Heart Diseases; Treatment Outcome
PubMed: 37622443
DOI: 10.20452/pamw.16547 -
Polish Archives of Internal Medicine Jun 2022Due to safety concerns about available antiarrhythmic drugs (AADs), reliable agents for termination of atrial fibrillation (AF) are requisite.
INTRODUCTION
Due to safety concerns about available antiarrhythmic drugs (AADs), reliable agents for termination of atrial fibrillation (AF) are requisite.
OBJECTIVES
The aim of the study was to evaluate the efficacy and safety of antazoline, a first‑generation antihistamine, for cardioversion of recent‑onset AF in the setting of an emergency department.
PATIENTS AND METHODS
This multicenter, retrospective registry covered 1365 patients (median [interquartile range] age, 69.0 [61.0-76.0] years, 53.1% men) with new‑onset AF submitted to urgent pharmacological cardioversion. AAD allocation was performed by the attending physician: antazoline alone was utilized in 600 patients (44%), amiodarone in 287 (21%), propafenone in 150 (11%), and ≥2 AADs in 328 patients (24%). Antazoline in monotherapy or combination was administered to 897 patients (65.7%). Matched antazoline and nonantazoline groups were identified using propensity score matching (PSM, n = 330). The primary end point was return to sinus rhythm within 12 hours after initiation of the treatment.
RESULTS
Before PSM, antazoline alone was superior to amiodarone (78.3% vs 66.9%; relative risk [RR], 1.17; 95% CI, 1.07-1.28; P <0.001) and comparable to propafenone (78.3% vs 72.7%; RR, 1.08; 95% CI, 0.97-1.20; P = 0.14) in terms of rhythm conversion rate. In the post‑PSM population, the rhythm conversion rate was higher among patients receiving antazoline alone than in the nonantazoline group (84.2% vs 66.7%; RR, 1.26; 95% CI, 1.11-1.43; P <0.001), and the risk of adverse events was comparable (P = 0.2).
CONCLUSIONS
Antazoline appears to be an efficacious agent for termination of AF in real‑world setting. Randomized controlled trials are required to evaluate its safety in specific patient populations.
Topics: Aged; Amiodarone; Antazoline; Anti-Arrhythmia Agents; Atrial Fibrillation; Electric Countershock; Female; Humans; Male; Propafenone; Propensity Score; Registries; Retrospective Studies; Treatment Outcome
PubMed: 35293200
DOI: 10.20452/pamw.16234 -
Annals of Noninvasive Electrocardiology... Sep 2017Antazoline is an old antihistaminic and new antiarrhythmic agent with unknown mechanisms of action which recently has been shown to effectively terminate atrial...
BACKGROUND
Antazoline is an old antihistaminic and new antiarrhythmic agent with unknown mechanisms of action which recently has been shown to effectively terminate atrial fibrillation. The aim of study was to examine the effects of antazoline on hemodynamic and ECG parameters.
METHODS
Antazoline was given intravenously in three 100 mg boluses to 10 healthy volunteers (four males, mean age 40 + 11 years). Hemodynamic and ECG parameters were measured using impedance cardiography [systolic (sBP), diastolic (dBP), mean (mBP) blood pressure, stroke volume (SV), cardiac output (CO), total peripheral resistance (TPR) and heart rate (HR), P wave, PR interval, QRS complex, QT and corrected QT (QTcF) interval]. Plasma concentration of antazoline was also measured.
RESULTS
Antazoline caused significant prolongation of P wave, QRS as well as QT and QTcF (101 ± 10 vs 110 ± 16 ms, p < .05, and 101 ± 12 vs 107 ± 12 ms, p < .05, 399 ± 27 vs 444 ± 23 ms, p < .05, and 403 ± 21 vs 448 ± 27 ms, p < .05, respectively). Also, a significant decrease in SV was noted (94.9 ± 21.8 vs 82.4 ± 19.6 ml, p < .05). A significant correlation between changes in plasma drug concentration and changes in CO, HR, and dBP was found.
CONCLUSIONS
Antazoline impairs slightly hemodynamics, significantly reducing SV. Significant prolongation of P wave and QRS duration corresponds to drug-induced prolongation of conduction, whereas QT prolongation represents drug-induced prolongation of repolarization.
Topics: Adult; Antazoline; Anti-Arrhythmia Agents; Blood Pressure; Electrocardiography; Female; Heart Rate; Hemodynamics; Histamine H1 Antagonists; Humans; Male; Reference Values; Stroke Volume
PubMed: 28236352
DOI: 10.1111/anec.12441 -
Virologica Sinica Jun 2021Hepatitis B virus (HBV) belongs to Hepadnaviridae family and mainly infects hepatocytes, which can cause acute or chronic hepatitis. Currently, two types of antiviral...
Hepatitis B virus (HBV) belongs to Hepadnaviridae family and mainly infects hepatocytes, which can cause acute or chronic hepatitis. Currently, two types of antiviral drugs are approved for chronic infection clinically: interferons and nucleos(t)ide analogues. However, the clinical cure for chronic infection is still rare, and it is a huge challenge for all researchers to develop high-efficiency, safe, non-tolerant, and low-toxicity anti-HBV drugs. Antazoline hydrochloride is a first-generation antihistamine with anticholinergic properties, and it is commonly used to relieve nasal congestion and in eye drops. Recently, an in vitro high-throughput evaluation system was constructed to screen nearly 800 compounds from the Food and Drug Administration (FDA)-approved Drug Library. We found that arbidol hydrochloride and antazoline hydrochloride can effectively reduce HBV DNA in the extracellular supernatant in a dose-dependent manner, with EC of 4.321 μmol/L and 2.910 μmol/L in HepAD38 cells, respectively. Moreover, the antiviral effects and potential mechanism of action of antazoline hydrochloride were studied in different HBV replication systems. The results indicate that antazoline hydrochloride also has a significant inhibitory effect on HBV DNA in the extracellular supernatant of Huh7 cells, with an EC of 2.349 μmol/L. These findings provide new ideas for screening and research related to HBV agents.
Topics: Antazoline; Antiviral Agents; DNA; DNA, Viral; Drug Repositioning; Hepatitis B; Hepatitis B virus; Hepatitis B, Chronic; Humans; Virus Replication
PubMed: 33165771
DOI: 10.1007/s12250-020-00306-2 -
Polish Archives of Internal Medicine Jan 2022There is insufficient evidence on the efficacy and safety of pharmacological cardioversion of recent‑onset atrial fibrillation (AF) in elderly patients. Antazoline has...
INTRODUCTION
There is insufficient evidence on the efficacy and safety of pharmacological cardioversion of recent‑onset atrial fibrillation (AF) in elderly patients. Antazoline has been shown to be effective and safe in various patient populations.
OBJECTIVES
We aimed to compare the clinical efficacy and safety of intravenous antazoline for pharmacological cardioversion of recent‑onset AF between patients aged 75 years or older and those younger than 75 years.
PATIENTS AND METHODS
This retrospective analysis was conducted using data derived from emergency room medical records of patients referred for pharmacological cardioversion due to symptomatic AF lasting less than 48 hours. The threshold for old age was set at 75 years. Conversion to sinus rhythm was considered the primary efficacy outcome. The primary safety outcome was defined as any adverse event requiring hospitalization.
RESULTS
The study included 334 participants, of whom 110 patients were aged 75 years or older (study group) and 224 patients were younger than 75 years (controls). Successful cardioversion was achieved using lower mean (SD) antazoline doses in the study group than in controls: 151 (59) mg vs 168 (58) mg (P = 0.039). Study and control groups showed a similar efficacy and safety of antazoline (78.2% and 68.3%, respectively; odds ratio [OR], 1.66; 95% CI, 0.98-1.31; P = 0.06) as well as hospitalization rates (0.9% and 4.0%, respectively; OR, 0.22; 95% CI, 0.03-1.75; P = 0.17).
CONCLUSIONS
Intravenous antazoline seems to be effective and safe for pharmacological cardioversion of recent‑onset AF in elderly patients in the emergency setting.
Topics: Aged; Antazoline; Anti-Arrhythmia Agents; Atrial Fibrillation; Electric Countershock; Humans; Retrospective Studies; Treatment Outcome
PubMed: 34643078
DOI: 10.20452/pamw.16120 -
International Journal of Molecular... Apr 2021The aim of this study was to develop magnetic molecularly imprinted nano-conjugate sorbent for effective dispersive solid phase extraction of antazoline (ANT) and its...
Magnetic Core-Shell Molecularly Imprinted Nano-Conjugates for Extraction of Antazoline and Hydroxyantazoline from Human Plasma-Material Characterization, Theoretical Analysis and Pharmacokinetics.
The aim of this study was to develop magnetic molecularly imprinted nano-conjugate sorbent for effective dispersive solid phase extraction of antazoline (ANT) and its metabolite, hydroxyantazoline (ANT-OH) in analytical method employing liquid chromatography coupled with mass spectrometry method. The core-shell material was characterized in terms of adsorption properties, morphology and structure. The heterogeneous population of adsorption sites towards ANT-OH was characterized by two K and two B values: K (1) = 0.319 µg L and B (1) = 0.240 μg g, and K (2) = 34.6 µg L and B (2) = 5.82 μg g. The elemental composition of magnetic sorbent was as follows: 17.55, 37.33, 9.14, 34.94 wt% for Si, C, Fe and O, respectively. The extraction protocol was optimized, and the obtained results were explained using theoretical analysis. Finally, the analytical method was validated prior to application to pharmacokinetic study in which the ANT was administrated intravenously to three healthy volunteers. The results prove that the novel sorbent could be useful in extraction of ANT and ANT-OH from human plasma and that the analytical strategy could be a versatile tool to explain a potential and pharmacological activity of ANT and ANT-OH.
Topics: Adsorption; Adult; Antazoline; Healthy Volunteers; Humans; Male; Molecularly Imprinted Polymers; Nanoconjugates; Solid Phase Extraction
PubMed: 33915912
DOI: 10.3390/ijms22073665 -
Annals of Cardiac Anaesthesia 2020Atrial fibrillation is the most common cardiac arrhythmia in western society affecting more than 35 million individuals worldwide annually. It is a common postoperative... (Review)
Review
Atrial fibrillation is the most common cardiac arrhythmia in western society affecting more than 35 million individuals worldwide annually. It is a common postoperative complication and may also occur spontaneously during general and local anesthesia administration. Aging, diabetes mellitus, hypertension, and cardiovascular diseases including cardiomyopathies, congenital cardiac anomalies, heart failure, myocardial ischemia, pericarditis, previous cardiac surgery, vascular disease, and valvular heart disease are some correlated factors. Beyond age, increased incidence of atrial fibrillation has been correlated to autoimmune system activation as it is the underlying mechanism of persistent atrial fibrillation development. Current research supports an association between the complement system activation and lymphocyte-pro-inflammatory cytokines release with the cardiac conduction system and atrial fibrosis. The loss of CD28 antigen from CD4+ CD28+ T lymphocytes seems to play a major role in atrial fibrillation development and prognosis. Except atrial fibrillation, a variety of additional electrocardiographic changes, resembling those with digitalis intoxication may accompany anaphylaxis and particularly Kounis syndrome. Histamine is one well-known mediator in allergic and inflammatory conditions as physiologically regulates several cardiovascular and endothelial functions with arrhythmogenic potential. The increased oxidative stress, measured by the redox potentials of glutathione, has been correlated with atrial fibrillation incidence and prevalence. The use of antazoline, a first-generation antihistamine agent used for rapid conversion of recent-onset atrial fibrillation in patients with preserved left ventricular function and for rapid atrial fibrillation termination during accessory pathway ablation denotes that anaphylaxis-induced histamine production could be the cause of atrial fibrillation at least in some instances. The anaphylaxis diagnosis in anesthesia can be challenging owing to the absence of cutaneous manifestetions such as flushing, urticaria, or angioedema. Anticoagulation for stroke prevention, rate and rhythm control medications, invasive methods such as radiofrequency ablation or cryoablation of pulmonary veins as well surgical ablation constitute the treatment basis of atrial fibrillation. Understanding the underlying mechanisms of atrial fibrillation by cardiologists, anesthesiologists and surgeons, as well as potential treatments, to optimize care is of paramount importance.
Topics: Anaphylaxis; Atrial Fibrillation; Cryosurgery; Humans; Radiofrequency Ablation
PubMed: 31929239
DOI: 10.4103/aca.ACA_100_19