Intravenous antazoline, a first-generation antihistaminic drug with antiarrhythmic properties, is a suitable agent for pharmacological cardioversion of atrial fibrillation induced during pulmonary vein isolation due to the lack of influence on atrio-venous conduction and high clinical effectiveness (AntaEP Study).

AIMS: Antazoline is a first-generation antihistaminic drug used primarily in eye drop formulations. When administered intravenously, antazoline displays antiarrhythmic properties resulting in a rapid conversion of recent-onset atrial fibrillation (AF) to sinus rhythm (SR). The aim of the study was to assess the influence of antazoline on atrio-venous conduction and other electrophysiological parameters in patients undergoing AF ablation. METHODS: An experimental prospective study. Patients scheduled for the first-time AF ablation, in SR and not on amiodarone were enrolled. Atrio-venous conduction assessment and invasive electrophysiological study (EPS) were performed before and after intravenous administration of 250 mg of antazoline. In case of AF induction during EPS, antazoline was administered until conversion to SR or a cumulative dose of 300 mg. RESULTS: We enrolled 14 patients: 13 (93%) men, mean age 63.4 (59.9-66.8) years, mean CHA2 DS2 -VASc score 1.6 (1.0-2.2). Antazoline was administered in a mean dose 257.1 (246.7-267.6) mg. Pulmonary vein potentials and atrial capture during pulmonary vein stimulation were present before and after the administration of antazoline. Wenckebach point and atrial conduction times did not change significantly, but atrio-ventricular node effective refractory period improved-324.7 (275.9-373.5) ms vs 284.3 (256.2-312.4) ms, P = 0.02. Antazoline was effective in all 5 (100%) cases of AF induction during EPS. There were no serious adverse events. CONCLUSION: Due to the lack of influence on atrio-venous conduction and high clinical effectiveness, antazoline may be suitable for pharmacological cardioversion of AF occurring during AF ablation.

Exposure to antazoline-naphazoline eye drops during pregnancy and the risk of congenital malformations: a Danish nationwide cohort study.

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.

Effect of Antazoline on Electrophysiological Properties of Atrial Muscle and Conduction System of the Heart.

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.

Efficacy and safety of antazoline in the rapid cardioversion of paroxysmal atrial fibrillation (the AnPAF Study).

AIMS: The aim of the study was to assess the clinical efficacy of antazoline, a first-generation anti-histaminic agent, in the rapid conversion of paroxysmal non-valvular atrial fibrillation (AF) to sinus rhythm in patients without heart failure. METHODS AND RESULTS: This study was a single center, randomized, double blind, placebo-controlled, superiority clinical trial. We enrolled patients with an AF episode lasting less than 43 h, in stable cardiopulmonary condition. Subjects who fulfilled the selection criteria were randomly assigned to receive intravenously either a placebo or up to 250 mg of antazoline. The primary end point was the conversion of AF to sinus rhythm confirmed in electrocardiogram (ECG). We enrolled 74 patients: 36 (48.6%) in the antazoline group and 38 (51.4%) in the control group. The mean age was 68 ± 12 years (range 31-90 years), 39 (53.3%) patients were male. The successful conversion of AF to sinus rhythm during the observation period was achieved in 26 (72.2%) patients treated with antazoline and 4 (10.5%) in the control group: RR 6.86 (95% CI: 2.66-17.72, P < 0.0001). Median time to conversion was 16.0 min in antazoline and 72.5 min in the control group (P = 0.0246). There were no cases of atrial tachycardia/flutter in the antazoline group. CONCLUSION: Intravenous antazoline was effective and safe in the rapid conversion of non-valvular paroxysmal atrial fibrillation to sinus rhythm in patients without heart failure. Clinical Trial Registration number: NCT01527279.

Antazoline for rapid termination of atrial fibrillation during ablation of accessory pathways.

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.

Clinical efficacy of antazoline in rapid cardioversion of paroxysmal atrial fibrillation--a protocol of a single center, randomized, double-blind, placebo-controlled study (the AnPAF Study).

BACKGROUND: Rapid conversion of atrial fibrillation (AF) to sinus rhythm may be achieved by the administration of class IA, IC and III antiarrhythmic drugs or vernakalant hydrochloride. However, that treatment may be related to potential pro-arrhythmia, lack of efficacy or the exceptionally high cost of a compound used. Antazoline is a first generation antihistaminic agent with chinidin-like properties. When administered intravenously, antazoline exerts a strong antiarrhythmic effect on supraventricular arrhythmia, especially on AF, facilitating rapid conversion to sinus rhythm. Despite a relative lack of published data antazoline has been marketed in Poland and widely used in cardiology wards and emergency rooms for many years due to its efficacy, safety and rapid onset of action within minutes of administration. METHODS/DESIGN: A randomized, double blind, placebo-controlled, superiority clinical trial was designed to assess clinical efficacy of antazoline in rapid conversion of AF to sinus rhythm. Eligible patients will present AF lasting less than 43 hours, will be in stable cardio-pulmonary condition and will have no prior history of advanced heart failure or significant valvular disease. Long-term antiarrhythmic therapy is not considered an exclusion criterion. Subjects who fulfill selection criteria will be randomly assigned to receive intravenously either antazoline or placebo in divided doses and observed for 1.5 hours after conversion to sinus rhythm or after the last i.v. bolus. Primary end point will be the conversion of AF to sinus rhythm confirmed in an electrocardiogram (ECG) during the observation period. Secondary end points will be comprised of time to conversion and return of AF during the observation period. Special consideration will be given to the observation of any adverse events. A sample size of 80 patients was calculated based on the following assumptions: two-tailed test, a type I error of 0.01, a power of 90%, efficacy of placebo 5%, efficacy of antazoline 50% and 20% drop-out rate to fulfill the criteria of intention-to-treat analysis. Due to the presumed lack of statistical power, the secondary end points and safety endpoints will be considered exploratory. CLINICAL TRIALS REGISTRY: ClinicalTrials.gov, NCT01527279.

A randomized controlled trial of intralesional bevacizumab injection on primary pterygium: preliminary results.

PURPOSE: To evaluate the efficacy and safety of intralesional injection of bevacizumab on primary pterygium treatment. METHODS: In this randomized controlled trial, each primary pterygium patient was randomized to receive either an intralesional injection of bevacizumab 2 mg (1 mg/0.04 mL) or a combination of topical antihistamine (antazoline HCl 0.05%) and vasoconstrictor (tetrahydrozoline HCl 0.04%) as a control. The main outcome measurements were symptoms and signs (including eye irritation, epiphora, redness, amount of discharge, inflammation and elevation of pterygium, and percentage of corneal pterygium area). RESULTS: A total of 74 pterygium eyes in 66 patients were randomized and allocated into a treatment group (N = 34) and a control group (N = 40). In the treatment group, there was a statistically significant reduction of symptoms (including irritation, photophobia, epiphora, redness, discharge, and blurred vision) and signs (inflammation and corneal pterygium area) compared with the baseline, up to at least 6 months. Between the treatment and control groups, no significant differences were found for all visits with respect to the (1) symptoms, (2) signs, and (3) percentage of corneal pterygium. CONCLUSIONS: Intralesional bevacizumab may have a therapeutic effect on symptoms and signs of primary pterygium for at least 6 months (ie, the follow-up period), with no serious ocular or systemic adverse effects.

Treatment of allergic conjunctivitis: results of a 1-month, single-masked randomized study.

PURPOSE: To compare the effects of topical antiallergic eyedrops in relieving the signs and symptoms of patients with allergic conjunctival pathology. METHODS: In this multicenter, single-masked, randomized study, 240 patients with signs and symptoms of allergic conjunctivitis were randomized to receive 1 of the following 8 treatments twice daily: cromolyn sodium/chlorpheniramine maleate, diclofenac, epinastine, fluorometholone, ketotifen, levocabastine, naphazoline/antazoline, and olopatadine. Clinical signs and symptoms were evaluated by a masked operator using a 10-point scale at the moment of enrollment (day 0) and at weeks 1, 2, and 4. The percentage of patients achieving at least a small (at least 50% reduction of the total scale score) or a good (at least 75%) improvement of signs and symptoms was calculated at each visit. Tolerability was also evaluated as the duration of discomfort after instillation. RESULTS: All drugs gave some improvement in symptoms in more than 85% of cases. Epinastine and olopatadine obtained at least a good relief of symptoms in 37% and 33% of cases at week 1. At the end of the study, good improvement of symptoms was obtained in at least 70% of patients by epinastine, ketotifen, fluorometholone, and olopatadine, whereas a 75% improvement for signs was obtained only by fluorometholone and ketotifen. Naphazoline/antazoline induced higher discomfort compared to the other study treatments (p<0.0001). CONCLUSIONS: The efficacy of epinastine, ketotifen, and olopatadine in the treatment of allergic conjunctivitis was comparable to fluorometholone. Naphazoline/antazoline had lower tolerability than the other study treatments.

[Antazoline/tetryzoline eyedrops in comparison with levocabastine eyedrops in acute allergic conjunctivitis]. / Antazolin/Tetryzolinhaltige Augentropfen im Vergleich zu Levocabastinhaltigen Augentropfen bei akuter allergischer Konjunktivitis.

BACKGROUND: Allergic conjunctivitis is one of the most frequent allergic diseases of the anterior eye segment. METHODS: This multicentre, clinical trial was an investigation to compare the antiallergic efficacy, local tolerance and safety of Antazolin/Tetryzolin eye drops and Levocabastine eye drops. 69 patients were treated over a 2 weeks course of therapy. The subjective and objective ocular symptoms were documented over the treatment period. RESULTS: Both eye drops reduced subjective and objective ocular symptoms effective. The difference between the treatments (p = 0.0395) was the faster onset of action of Antazolin/Tetryzolin 30 minutes after administration of the first drop of trial medication. CONCLUSION: A fast and effective onset of action is of high clinical relevance. Therefore the benefits of using Antazolin/Tetryzolin eye drops was clearly outweigh.

[A case of allergic reaction to the sting by the bee]. / Przypadek reakcji alergicznej na ukaszenie przez ose.

The authors described a case of an insect sting allergy, of a 19 year old patient. They discuss the treatment and prevention in such cases and situations.

Otrivine-antistin-pupil, corneal and conjunctival responses to topical administration.

The ocular effects of Otrivine-Antistin eyedrops have been measured in a placebo controlled single-blind study in sixteen healthy volunteers. The drops produced mild sympathomimetic responses in the eye but had no effect on corneal sensitivity or on intraocular pressure. The evidence indicates that use of Otrivine-Antistin imposes no risk to the subject.

Antazoline as an adjuvant in immunosuppressive therapy in renal transplant patients.

The survival of transplanted cadaver kidneys was compared in a group of 33 first-transplant patients treated with antazoline (Antistine) in addition to conventional immunosuppressive therapy (group A) and a group of 36 patients receiving immunosuppressive therapy only (group B). After 1 year, the transplant survival rate was 79% in group A as compared to 56% in group B (P less than 0.05). The difference which was still present after 2 and 5 years could not be attributed to any other factors that might have influenced the survival rate. Antazoline appears above all to diminish the intensity of moderately severe rejection episodes, which often lead to graft loss inducing a chronic type of rejection reaction. However, the frequency of rejection crises during the first 4 months and the percentages of patients without rejection or with primary irreversible rejection crises were practically the same in the two groups. The mechanism of action underlying this potentially important immunosuppressive effect of antazoline is as yet not clarified.

An in vitro method simulating drug release from viscous eye drops in rabbit and man.

A method has been developed using a diffusion cell in an attempt to determine the drug release from viscous solutions under conditions simulating the blinking movements in the rabbit and human eye. Diffusion coefficients were determined at rest and at different velocities. For the solutions at rest, corresponding with the conditions at the surface of the rabbit cornea, the diffusion velocity decreases with increasing viscosity. When the solution is moved at a velocity corresponding to that of lachrymal fluid at the surface of the human eye, the influence of viscosity may be neglected.

Antazoline in the treatment of cardiac arrhythmias.

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.