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Cardiovascular Drugs and Therapy Apr 2018Antazoline is a first-generation antihistaminic agent with additional anticholinergic properties and antiarrhythmic potential. Recent data shows its high effectiveness...
PURPOSE
Antazoline is a first-generation antihistaminic agent with additional anticholinergic properties and antiarrhythmic potential. Recent data shows its high effectiveness in sinus rhythm restoration among patients with paroxysmal atrial fibrillation. The effect of antazoline on electrophysiological parameters of the heart in vivo has not yet been examined. The aim of this study was to evaluate changes in electrophysiological parameters of the heart muscle and conduction system as a response to increasing doses of antazoline.
METHODS
After successful ablation of supraventricular arrhythmias, the electrophysiological parameters: sinus rhythm cycle length (SRCL), AH, HV, QRS, QT, QTc intervals, Wenckebach point (WP), sinus node recovery period (SNRT), intra- (hRA-CSos) and interatrial conduction time (hRA-CSd), right and left atrium refractory period (RA-; LA-ERP), and atrioventricular node refractory period (AVN-ERP) were assessed initially and after 100, 200, and 300 mg of antazoline given intravenously.
RESULTS
Fifteen patients (8 males, 19-72 years old) undergoing EPS and RF ablation were enrolled. After 100 mg bolus, a significant reduction in SRCL was noticed. After antazoline administration, significant prolongation of HV, QRS, QTc, hRA-CSos, hRA-CSd intervals, RA- and LA-ERP and reduction of SRCL were observed. After a total dose of 300 mg, QT interval prolonged significantly. Increasing the dose of antazoline had no impact on AH, Wenckebach point, AVN-ERP, and SNRT.
CONCLUSION
Antazoline has an effect on electrophysiological parameters of the atrial muscle and has rapid onset of action. No negative effect on sinus node function and atrioventricular conduction in a unique property among antiarrhythmic drugs.
Topics: Action Potentials; Adult; Aged; Antazoline; Anti-Arrhythmia Agents; Atrial Flutter; Catheter Ablation; Dose-Response Relationship, Drug; Female; Heart Atria; Heart Conduction System; Heart Rate; Humans; Male; Middle Aged; Papillary Muscles; Tachycardia, Atrioventricular Nodal Reentry; Treatment Outcome; Young Adult
PubMed: 29623481
DOI: 10.1007/s10557-018-6787-9 -
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 -
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 -
Cardiology Journal 2014To assess safety and efficacy of antazoline for termination of atrial fibrillation (AF) occurring during ablation of accessory pathways (AP).
BACKGROUND AND AIM
To assess safety and efficacy of antazoline for termination of atrial fibrillation (AF) occurring during ablation of accessory pathways (AP).
METHODS
We analyzed electrophysiological mechanism of antazoline (changes in A-A interval) and the percentage of pre-excited QRS complexes before and after antazoline administration. The total dose administered and the time from the start of injection to sinus rhythm restoration were also measured.
RESULTS
Out of consecutive 290 patients with Wolff-Parkinson-White syndrome undergoing radiofrequency (RF) ablation, 12 (4.1%) (4 females, mean age 36 ± 20 years) developed sustained AF which did not stop spontaneously within 10 min, and antazoline in 100 mg repeated boluses was administered. In all 12 patients the drug restored sinus rhythm after a mean of 425 ± 365 s (range 43-1245 s) using a mean cumulative dose of 176 ± 114 mg (range 25-400 mg). The drug slightly prolonged R-R intervals during AF (from 383 ± 106 to 410 ± 70 ms) and reduced the percentage of fully pre-excited QRS complexes (from 35% to 26%). Intracardiac recordings showed gradual increase in A-A intervals, as well as regularization and decreasing fractionation of atrial activity following drug injection (mean A-A interval of 162 ± 30 ms at baseline vs. 226 ± 26 ms shortly before sinus rhythm restoration, p < 0.001). AP was not completely blocked in any patient which enabled continuation of ablation.
CONCLUSIONS
Antazoline safely and rapidly converts AF into sinus rhythm during ablation of AP. The drug does not block AP completely, enabling continuation of ablation. The drug converting AF into more organized atrial activity (atrial flutter/tachycardia) before sinus rhythm resumption.
Topics: Accessory Atrioventricular Bundle; Adult; Antazoline; Atrial Fibrillation; Catheter Ablation; Dose-Response Relationship, Drug; Electrocardiography; Female; Follow-Up Studies; Heart Atria; Heart Rate; Histamine H1 Antagonists; Humans; Injections, Intravenous; Intraoperative Complications; Male; Wolff-Parkinson-White Syndrome
PubMed: 23990192
DOI: 10.5603/CJ.a2013.0121 -
European Neuropsychopharmacology : the... Aug 2004Experimental studies have indicated that the central histaminergic system plays an important role in the inhibition of seizures through the stimulation of histamine H1... (Comparative Study)
Comparative Study
Experimental studies have indicated that the central histaminergic system plays an important role in the inhibition of seizures through the stimulation of histamine H1 receptors. H1 receptor antagonists, including classical antiallergic drugs, occasionally may induce convulsions in healthy children and patients with epilepsy. The purpose of this study was to investigate the effects of antazoline and ketotifen (two H1 receptor antagonists) on the anticonvulsant activity of antiepileptic drugs against maximal electroshock (MES)-induced convulsions in mice. The following antiepileptic drugs were used: valproate, carbamazepine, diphenylhydantoin and phenobarbital. In addition, the effects of antiepileptic drugs alone or in combination with antazoline or ketotifen were studied on long-term memory (tested in the passive avoidance task) and motor performance (evaluated in the chimney test), acutely and after 7-day treatment with these H1 receptor antagonists. The influence of antazoline and ketotifen on the free plasma and brain levels of the antiepileptics was also evaluated. Antazoline (at 0.5 mg/kg), given acutely and after 7-day treatment, significantly diminished the electroconvulsive threshold. Similarly, ketotifen, after acute and chronic doses of 8 mg/kg markedly reduced the threshold for electroconvulsions. In both cases, antazoline and ketotifen were without effect upon this parameter at lower doses. Antazoline (0.25 mg/kg) significantly raised the ED50 value of carbamazepine against MES (both, acutely and after 7-day treatment). Furthermore antazoline (0.25 mg/kg) also reduced the anticonvulsant activity of diphenylhydantoin, but only after repeated administration, without modifying the brain and free plasma level of this drug. Moreover, valproate and phenobarbital did not change their protective activity when combined with antazoline. Ketotifen (4 mg/kg) possessed a biphasic action, acutely it enhanced the anticonvulsant action of carbamazepine and phenobarbital while, following 7-day treatment, reduced the antiseizure activity of carbamazepine. Ketotifen did not affect the free plasma or brain levels of antiepileptics tested. Only acute antazoline (0.25 mg/kg) applied with valproate impaired the performance of mice evaluated in the chimney test. Ketotifen (4 mg/kg) co-administered with conventional antiepileptic drugs impaired motor coordination in mice treated with valproate, phenobarbital or diphenylhydantoin. Acute and chronic antazoline (0.25 mg/kg) alone or in combination with antiepileptic drugs did not disturb long-term memory, tested in the passive avoidance task. Similarly, ketotifen (4 mg/kg) did not impair long-term memory, acutely and after 7-day treatment. However, valproate alone or in combination with chronic ketotifen (4 mg/kg) worsened long-term memory. The results of this study indicate that H1 receptor antagonists, crossing the blood brain barrier, should be used with caution in epileptic patients. This is because antazoline reduced the protective potential of diphenylhydantoin and carbamazepine. Also, ketotifen reduced the protection offered by carbamazepine and elevated the adverse activity of diphenylhydantoin, phenobarbital and valproate.
Topics: Animals; Antazoline; Anticonvulsants; Avoidance Learning; Behavior, Animal; Brain; Brain Chemistry; Confidence Intervals; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Synergism; Electroshock; Histamine H1 Antagonists; Ketotifen; Male; Mice; Motor Activity; Psychomotor Performance; Seizures; Time Factors
PubMed: 15163441
DOI: 10.1016/j.euroneuro.2003.09.005 -
Polish Archives of Internal Medicine Apr 2024
Topics: Atrial Fibrillation; Humans; Anti-Arrhythmia Agents
PubMed: 38666721
DOI: 10.20452/pamw.16741 -
European Journal of Pharmacology Apr 1997In vivo effects of an imidazoline devoid of alpha2-adrenoceptor antagonistic properties, antazoline, on insulin secretion and glycemia were investigated both in fasted...
In vivo effects of an imidazoline devoid of alpha2-adrenoceptor antagonistic properties, antazoline, on insulin secretion and glycemia were investigated both in fasted rats and dogs. In both species, antazoline (1.5 mg/kg i.v.) transiently increased insulinemia without affecting basal plasma glucose levels. In contrast, during an i.v. glucose tolerance test, antazoline markedly potentiated insulin release and thus increased the glucose disappearance rate. In rats, during an oral glucose tolerance test, the intragastric administration of antazoline (1.5 mg/kg) clearly enhanced insulin secretion and reduced hyperglycemia. In dogs provided with a venous pancreatico-duodenal bypass, antazoline (0.5 mg/kg i.v.) induced an immediate and transient increase in insulin and somatostatin but not in glucagon pancreatico-duodenal outputs. In conclusion, intravenously and orally administered, the imidazoline antazoline is able to stimulate insulin secretion in vivo and improve glucose tolerance. The imidazoline compounds could therefore have a potential therapeutic relevance as new antihyperglycemic insulinotropic agents.
Topics: Animals; Antazoline; Blood Glucose; Dogs; Glucose Tolerance Test; Injections, Intravenous; Insulin; Male; Rats; Rats, Wistar
PubMed: 9145778
DOI: 10.1016/s0014-2999(97)00126-x -
Postgraduate Medical Journal May 1972Antazoline was administered in sixty-five episodes of various types of cardiac arrhythmia. A complete suppression of the ectopic beats was achieved in five out of six...
Antazoline was administered in sixty-five episodes of various types of cardiac arrhythmia. A complete suppression of the ectopic beats was achieved in five out of six episodes of premature atrial systoles and in twenty-one of the twenty-four episodes of ventricular premature systoles. Conversion to sinus rhythm was observed in seven out of ten and four out of five episodes of paroxysmal atrial and nodal tachycardia respectively. Six out of ten episodes of ventricular tachycardia were controlled by intravenous therapy. However, the drug proved to be ineffective in cases of atrial fibrillation. The side-effects were few and transitory, consisting of nausea, vomiting and drowsiness.
Topics: Administration, Oral; Adolescent; Adult; Aged; Antazoline; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Electrocardiography; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Treatment Outcome; Young Adult
PubMed: 18557243
DOI: 10.1136/pgmj.48.559.304 -
Acta Ophthalmologica Aug 2019To investigate whether exposure to antazoline-naphazoline eye drops in the first trimester of pregnancy was associated with an increased risk of malformations in humans.
PURPOSE
To investigate whether exposure to antazoline-naphazoline eye drops in the first trimester of pregnancy was associated with an increased risk of malformations in humans.
METHODS
All women giving live birth between 1997 and 2011 in Denmark were included in this nationwide cohort study. All women redeeming at least one prescription of antazoline-naphazoline eye drops during the first 84 days of pregnancy were identified. Logistic regression was used to estimate the odds ratios of malformations among exposed offspring compared to non-exposed offspring.
RESULTS
We identified 977 706 births between 1997 and 2011. A total of 3061 women (0.32%) were exposed to antazoline-naphazoline eye drops in the first trimester of pregnancy. The rate of congenital malformations was 3.0% (n = 93) in exposed offspring and 3.5% (n = 33 594) in unexposed offspring. First-trimester exposure to antazoline-naphazoline was not associated with major congenital malformations overall (odds ratio: 0.88, 95% confidence interval: 0.71-1.09) or with any specific major malformation. The number of redeemed prescriptions was unchanged during all trimesters of pregnancy as compared to before and after pregnancy (p < 0.05).
CONCLUSION
Exposure to antazoline-naphazoline eye drops in the first trimester of pregnancy appears not to be associated with increased teratogenic risk.
Topics: Abnormalities, Drug-Induced; Adult; Antazoline; Anti-Allergic Agents; Denmark; Female; Follow-Up Studies; Humans; Incidence; Infant, Newborn; Male; Naphazoline; Nasal Decongestants; Ophthalmic Solutions; Population Surveillance; Pregnancy; Pregnancy Outcome; Pregnancy Trimester, First; Registries; Retrospective Studies; Risk Factors; Young Adult
PubMed: 30479070
DOI: 10.1111/aos.13980 -
Polish Archives of Internal Medicine Apr 2024Antazoline is a frequently used antiarrhythmic drug (AAD); however, to date, no randomized controlled trial has evaluated its efficacy and safety for cardioversion of... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Antazoline is a frequently used antiarrhythmic drug (AAD); however, to date, no randomized controlled trial has evaluated its efficacy and safety for cardioversion of recent‑onset atrial fibrillation (AF) in comparison with other approved AADs.
OBJECTIVES
This study aimed to compare clinical efficacy and safety of antazoline and propafenone for a rapid conversion of nonvalvular paroxysmal AF to sinus rhythm in patients without heart failure.
PATIENTS AND METHODS
This was a single‑center, randomized, double‑blind study. It included patients with AF (lasting <48 hours) who were in a stable cardiopulmonary condition and eligible for cardioversion. The individuals who fulfilled the inclusion criteria were randomly assigned to receive either antazoline (up to 300 mg) or propafenone (up to 140 mg) intravenously. The primary end point was conversion of AF to sinus rhythm confirmed on electrocardiography.
RESULTS
Overall, 94 participants (46 [48.9%] in the antazoline group and 48 [51.1%] in the propafenone group) were included. The mean (SD) age was 67.5 (14) years, and 40 participants (42.5%) were men. Successful AF conversion was observed in 29 patients (63%) from the antazoline group and 25 individuals (52.1%) from the propafenone group (P = 0.39). The median time to conversion was 10 minutes in the antazoline group and 30 minutes in the propafenone group (P = 0.03). Severe adverse events were observed in 5 patients (10.8%) treated with antazoline and 5 individuals (10.4%) who received propafenone.
CONCLUSIONS
Intravenous antazoline demonstrated efficacy and safety comparable to those of intravenous propafenone for acute conversion of nonvalvular paroxysmal AF to sinus rhythm in patients without heart failure.
Topics: Humans; Propafenone; Atrial Fibrillation; Double-Blind Method; Male; Antazoline; Female; Anti-Arrhythmia Agents; Middle Aged; Aged; Treatment Outcome
PubMed: 38166357
DOI: 10.20452/pamw.16657