piperidines and Syncope

An 86-year-old man was admitted with a 3-day history of melaena and syncope. He was haemodynamically compromised and anaemic on presentation. His only medical history was mild Alzheimer's disease diagnosed 6 months prior. For this, he was on donepezil, a cholinesterase inhibitor (ChEI), with a recent dose increase 3 months earlier. After fluid resuscitation with packed red cells, an endoscopy was performed, which showed an acute duodenal ulcer. This was treated with a high-dose proton pump inhibitor. The patient recovered well and was discharged on donepezil with the addition of a gastro-protective proton pump inhibitor. In view of other absent risk factors of upper gastrointestinal haemorrhage, donepezil was the likely causative agent. ChEIs are associated with frequent side effects and increased hospitalisation due to central and peripheral increase in acetylcholine. With this case report, we review the literature of side effects related to ChEIs, where the mechanisms of action, complications and appropriate management are discussed.

Topics: Aged, 80 and over; Alzheimer Disease; Cholinesterase Inhibitors; Donepezil; Duodenal Ulcer; Endoscopy; Gastrointestinal Hemorrhage; Humans; Indans; Lansoprazole; Male; Piperidines; Proton Pump Inhibitors; Syncope

When otherwise unexplained, syncope in patients with Alzheimer's disease may be attributed to bradycardia caused by cholinesterase inhibitors. We studied prospectively the clinical events and cardiovascular changes occurring during treatment with donepezil in patients with Alzheimer's disease.. Consecutive patients presenting with mild-to-moderate Alzheimer's disease were included in the study. Their clinical characteristics, blood pressure, heart rate and electrocardiogram were recorded before (baseline) and during treatment with donepezil. The drug was administered at a dosage of 5 mg/day for 1 month and 10 mg/day for the following 7 months, as tolerated. We compared the baseline observations with those made at 1, 2 and 8 months of donepezil treatment. We also examined the effects of negatively chronotropic or dromotropic drugs concomitantly administered with donepezil.. Thirty patients were included in the study, of whom 43% were taking negatively chronotropic or dromotropic drugs. The first month of therapy (donepezil 5 mg/day) was completed by 26 patients. During the 7-month high-dosage phase (10 mg/day), four patients dropped out of the study; thus, 22 patients completed the full 8 months of the study. The mean heart rate was 66 +/- 8 beats/min at baseline in the overall study population. This decreased significantly to 62 +/- 9, 61 +/- 7 and 62 +/- 8 beats/min at the 1, 2 and 8 month timepoints, respectively (all p = 0.002 vs baseline). Among patients not receiving negatively chronotropic or dromotropic drugs, heart rate decreased significantly over the course of the study (from 67 +/- 8 beats/min at baseline to 62 +/- 8 beats/min at 1 month, 62 +/- 7 beats/min at 2 months and 62 +/- 8 beats/min at 8 months [all p = 0.005 vs baseline]). There was no significant change in heart rate in patients who were receiving negatively chronotropic or dromotropic drugs. The PR interval increased over the course of the study in all patient groups, but these changes were only statistically significant in the group of patients who were not taking negatively chronotropic or dromotropic drugs (155 +/- 23ms at baseline vs 158 +/- 21, 160 +/- 22 and 163 +/- 24ms at the 1, 2 and 8 month timepoints; all p = 0.02 vs baseline). One patient developed syncope due to orthostatic hypotension; there were no cases of bradycardia-induced syncope. Gastrointestinal manifestations were reported in ten of the study patients. Abdominal pain and vomiting were the reasons for study termination in five of the eight patients who did not complete the trial.. A donepezil-induced decrease in heart rate and increase in PR interval were observed only in patients with Alzheimer's disease who were not treated with negatively chronotropic or dromotropic drugs. These changes were not associated with bradycardia-induced syncope.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Blood Pressure; Cardiovascular System; Cholinesterase Inhibitors; Donepezil; Drug Administration Schedule; Electrocardiography; Female; Follow-Up Studies; Heart Rate; Humans; Indans; Male; Piperidines; Prospective Studies; Risk; Syncope

Heart rate variability is used to assess cardiovascular autonomic function. The cholinesterase inhibitor donepezil potentially affects parasympathetic activity. Twenty participants with Alzheimer's disease or dementia with Lewy bodies were treated with donepezil in a pilot study. Power spectral analysis was used to analyse 5 min of beat-to-beat RR interval data in 15 cases. Heart rate variability was significantly reduced following treatment with donepezil; mainly for high frequency (median changed from 581 to 78 ms2; p = 0.001) but also for total power (median changed from 1,563 to 844 ms2; p = 0.047). Donepezil may adversely influence cardiovascular autonomic control. These results indicate the need for larger controlled trials to further investigate the cardiovascular effects of donepezil.

Topics: Aged; Autonomic Nervous System; Cardiovascular System; Cholinesterase Inhibitors; Dementia; Donepezil; Female; Heart Rate; Humans; Indans; Male; Pilot Projects; Piperidines; Regression Analysis; Sampling Studies; Syncope

Oral tyrosine kinase inhibitors (TKIs) are becoming increasingly common in oncology practice due to ease of administration and patient preference. This class of medications is relatively unknown to emergency physicians.. Here we present a case of electrical storm (ES) thought to be associated with ibrutinib, a TKI. The ES was unabated despite antidysrhythmic therapy and electrical cardioversion, and was treated with supportive care, which eventually included the use of extracorporeal membrane oxygenation. This patient had no risk factors or apparent causes of recurrent ventricular tachycardia. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: ES has not previously been described with ibrutinib, but may be associated with off-target effects of the drug.

Topics: Adenine; Amiodarone; Anti-Arrhythmia Agents; Antineoplastic Agents; Cardiotonic Agents; Electric Countershock; Electrocardiography; Electrophysiology; Emergency Service, Hospital; Extracorporeal Membrane Oxygenation; Humans; Intensive Care Units; Intra-Aortic Balloon Pumping; Isoproterenol; Lidocaine; Magnesium; Male; Middle Aged; Piperidines; Pyrazoles; Pyrimidines; Respiration, Artificial; Syncope; Tachycardia, Ventricular; Torsades de Pointes; Waldenstrom Macroglobulinemia; Workforce

An 80-year-old woman with Alzheimer's dementia presented with diarrhoea, vomiting and worsening confusion following an increase in donepezil dose from 5 to 10 mg. The ECG revealed prolongation of QTc interval. Soon after admission, she became unresponsive with polymorphic ventricular tachycardia (VT). Cardiopulmonary resuscitation with a 200 J shock was successful in establishing cardiac output. Following the discontinuation of donepezil, the QTc interval normalised and no further arrhythmias were recorded. Treatment with anticholinesterase inhibitors may result in life-threatening VT. Vigilance is required for the identification of this condition in patients presenting with presyncope, syncope or seizures.

Topics: Aged, 80 and over; Alzheimer Disease; Cardiopulmonary Resuscitation; Donepezil; Electrocardiography; Female; Humans; Indans; Long QT Syndrome; Nootropic Agents; Piperidines; Seizures; Syncope; Torsades de Pointes

Donepezil is a commonly used drug in older people that due to its procholinergic effects can provoke bradycardia and neurocardiogenic syncope. Donepezil is metabolized by the cytochrome P450 isozyme 3A4 (CYP3A4). Clarithromycin is a potent inhibitor of CYP3A4, and patients taking both of these drugs may be at increased risk of cardiac adverse events.. The aim of this study was to evaluate the association between recent use of clarithromycin and adverse cardiovascular events in elderly patients receiving donepezil.. A population-based, nested case-control study using provincial healthcare databases was conducted. The base cohort was made up of persons 66 years of age or older who were prescribed donepezil and also were prescribed clarithromycin, erythromycin, azithromycin, cefuroxime, moxifloxacin or levofloxacin. Cases were those members of the base cohort hospitalized for bradycardia, syncope or complete atrioventricular block. For each case patient, five controls were matched according to age, sex and residence (community or long-term care).. Between July 2002 and March 2010, 17,712 patients continuously receiving donepezil were prescribed one of the antibacterials. In 1400 person-years of follow-up, 59 cases were identified. As compared with azithromycin, there was no statistically significant association between use of clarithromycin in donepezil users and subsequent adverse cardiovascular events (odds ratio 0.67; 95% CI 0.28, 1.63). There was no significant risk associated with exposure to either cefuroxime or respiratory quinolones.. The use of clarithromycin in elderly donepezil users did not significantly increase the risk of adverse cardiovascular outcomes. However, our study cannot rule out a possible small increase in risk. Although antibacterials can be beneficial, care should be taken in selecting antibacterials for use in older people receiving donepezil.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Atrioventricular Block; Bradycardia; Cardiovascular Diseases; Case-Control Studies; Cholinesterase Inhibitors; Clarithromycin; Cohort Studies; Cytochrome P-450 CYP3A Inhibitors; Donepezil; Drug Interactions; Drug Prescriptions; Enzyme Inhibitors; Female; Humans; Indans; Macrolides; Male; Ontario; Piperidines; Syncope

An 83-year-old female, who had a history of anterior myocardial infarction, was treated for Alzheimer's disease with donepezil. She suffered from repeated diarrhea and vomiting, and experienced syncope. She was admitted to our hospital and was diagnosed with acute colitis and syncope. On admission, her heart rate was 54 beats/min with regular rhythm. Laboratory data showed a low plasma potassium level. Electrocardiogram (ECG) showed poor R progression, ST elevation, negative T in precordial leads, and marked QT prolongation. Transthoracic echocardiogram showed the enlargement of the left atrium and aneurysmal area at the apex. Torsades de Pointes (TdP) with syncope and convulsion were confirmed on ECG monitoring twice after admission. We treated her with potassium chloride and started magnesium sulfate and lidocaine, and then added isoprenaline injection. After these treatments, her heart rate increased and we did not detect TdP again. With the aging population in Japan, prescriptions for donepezil are increasing. We have to be vigilant for syncope in patients taking donepezil, which is possibly related to QT prolongation and TdP.

Topics: Aged, 80 and over; Alzheimer Disease; Cholinesterase Inhibitors; Colitis; Donepezil; Electrocardiography; Female; Humans; Indans; Isoproterenol; Lidocaine; Long QT Syndrome; Magnesium Sulfate; Nootropic Agents; Piperidines; Potassium Chloride; Syncope; Torsades de Pointes; Treatment Outcome

Topics: Alzheimer Disease; Cholinesterase Inhibitors; Germany; Heart Diseases; Humans; Indans; Piperidines; Syncope

Treatment of Alzheimer's disease (AD) with cholinesterase inhibitors carries a theoretical risk of precipitating bradycardia. Though syncope occurs in patients with AD, its aetiology is unclear. The aim of this study was to determine the causes of syncope in patients with AD who were treated with donepezil and hospitalised for evaluation of syncope.. We studied 16 consecutive patients (12 women, 4 men) with AD aged 80 +/- 4 years who were hospitalised for evaluation of syncope. All patients underwent staged evaluation, ranging from physical examination to electrophysiological testing.. The mean dose of donepezil administered was 7.8 mg/day, and the mean duration of donepezil treatment at the time of syncope was 12 +/- 8 months. A cause of syncope was identified in 69% of patients. Carotid sinus syndrome was observed in three patients, complete atrioventricular block in two patients, sinus node dysfunction in two patients, severe orthostatic hypotension in two patients and paroxysmal atrial fibrillation in one patient. A brain tumour was discovered in one patient. No cause of syncope was found in 31% of patients despite comprehensive investigation. Repetition of the investigations after discontinuation of donepezil was noncontributory.. In patients with AD treated with donepezil, a noninvasive evaluation identified a probable cause of syncope in over two-thirds of patients. Cardiovascular abnormalities were predominant. Noninvasive evaluation is recommended before discontinuing treatment with cholinesterase inhibitors in patients with AD and unexplained syncope.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Cholinesterase Inhibitors; Donepezil; Female; Humans; Indans; Male; Piperidines; Syncope

Topics: Aged; Alzheimer Disease; Cholinesterase Inhibitors; Donepezil; Electrocardiography, Ambulatory; Female; Humans; Indans; Piperidines; Syncope

We describe three cases of patients with Alzheimer's disease who presented with cardiac syncope soon after initiation of a cholinesterase inhibitor therapy (donepezil). Bradyarrhythmia was documented in two patients, considered probable in one, and was presumed related to the cholinergic therapy. Pacemaker implantation seemed justified rather than donepezil cessation. More over, it permitted an increase in donepezil dosage.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Bradycardia; Cholinesterase Inhibitors; Donepezil; Female; Humans; Indans; Male; Pacemaker, Artificial; Piperidines; Syncope

To report a case of QT prolongation and syncopal episodes resulting from concomitant use of cisapride and agents known to inhibit its metabolism.. A 53-year-old white woman was involved in two motor vehicle accidents on the same day after experiencing syncopal episodes. Cardiac and neurologic evaluations were negative; the syncopal episodes were attributed to QT prolongation associated with the concomitant use of cisapride and agents known to inhibit its metabolism.. This is the first case published in the English-language literature describing QT prolongation resulting from the concomitant use of cisapride and agents known to inhibit its metabolism. Clarithromycin inhibits CYP3A4, the isoenzyme responsible for the metabolism of cisapride. Concomitant administration of cisapride with agents known to inhibit CYP3A4 (i.e., azole antifungals, erythromycin, clarithromycin) may result in elevated cisapride concentrations. Elevated cisapride concentrations have been associated with QT prolongation, syncopal episodes, and cardiac dysrhythmias.. Acquired QT prolongation is a well-recognized adverse effect of several drugs. Recognition of newer drugs and drug combinations that place patients at risk for this potentially fatal adverse event is imperative for appropriate monitoring and prevention.

Topics: Accidents, Traffic; Anti-Bacterial Agents; Anti-Ulcer Agents; Cisapride; Clarithromycin; Cytochrome P-450 Enzyme System; Drug Interactions; Electrocardiography; Female; Gastrointestinal Agents; Humans; Long QT Syndrome; Middle Aged; Omeprazole; Piperidines; Syncope

Cardiotoxicity of cisapride may increase when this drug is associated with ranitidine.. A 37-day old term infant, treated with cisapride (1.2 mg/kg/d) and ranitidine for regurgitations, was hospitalized for malaise. A prolonged QT interval (with isolate ventricular extrasystoles), noted at admission, disappeared rapidly after cisapride withdrawal. Linkage to cisapride was probable, promoted by high dosage and cisapride metabolism inhibition by ranitidine, but its plasma concentration was not measured.. This case report stresses the problem of cisapride dosage in infants and the question of an interaction between cisapride and ranitidine.

Topics: Anti-Ulcer Agents; Cisapride; Dose-Response Relationship, Drug; Drug Therapy, Combination; Gastroesophageal Reflux; Histamine H2 Antagonists; Humans; Infant; Long QT Syndrome; Male; Piperidines; Ranitidine; Syncope

Respiratory complications of gastroesophageal reflux disease that have been reported include hoarseness, wheezing, bronchospasm, stridor, laryngitis, and chronic cough. Syncope as a manifestation of gastroesophageal reflux disease-induced cough has not been described in the literature. We present an unusual case of gastroesophageal reflux that resulted in frequent cough-induced syncope. Treatment ultimately consisted of a laparoscopic Nissen fundoplication which resulted in sustained relief from both cough and syncope.

Topics: Adult; Cisapride; Cough; Drug Therapy, Combination; Gastroesophageal Reflux; Humans; Male; Monitoring, Physiologic; Omeprazole; Piperidines; Syncope

Antiarrhythmic therapy is known to be associated with a significant risk of adverse cardiac reactions, including a proarrhythmic response. This study assessed in 1,330 patients followed up for 292 +/- 393 days the predictive value for cardiovascular safety of a system by which patients were classified according to ventricular arrhythmias on entry, presence or absence of organic heart disease and drug dose for flecainide acetate. Baseline arrhythmia subgroups included patients with premature ventricular complexes only, nonsustained ventricular tachycardia, and sustained ventricular tachycardia. Proarrhythmic events occurred in 6.8% of patients overall and were serious in 2.3% and lethal in 1.0%. However, proarrhythmia was highly dependent on arrhythmia class on entry: serious nonlethal proarrhythmic events occurred in 6.6% of patients with sustained ventricular tachycardia, only 0.9% with nonsustained ventricular tachycardia and 0% with premature ventricular complexes (p less than 0.01). Proarrhythmic death occurred in 3.1% of patients with sustained ventricular tachycardia, 0.2% with nonsustained ventricular tachycardia and 0% with premature ventricular complexes only (p less than 0.01). Proarrhythmia was also influenced by the presence of structural heart disease: serious nonlethal proarrhythmia occurred in 2.6% of patients with versus 0.4% of those without organic heart disease, and death occurred in 1.2 versus 0%, respectively. These adverse events were also dependent on dosing regimen. Flecainide caused premature discontinuation due to new or worsened heart failure in 1.4% of patients, all with underlying organic heart disease; however, heart failure was not clearly related to dose or type of arrhythmia. Symptomatic conduction disturbances occurred in 2.2%, and were predicted by preexistent sinus node disease but not by other baseline features.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Arrhythmias, Cardiac; Death, Sudden; Drug Administration Schedule; Flecainide; Heart Failure; Humans; Inpatients; Outpatients; Piperidines; Risk; Syncope

Topics: Adult; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Electrocardiography; Female; Flecainide; Humans; Middle Aged; Piperidines; Syncope; Tachycardia

Twenty-six patients (19 men and 7 women) with symptomatic ventricular tachycardia (VT) were studied using invasive and noninvasive techniques to induce VT. Of the study population, 12% had syncope and VT on Holter monitoring, 30% had cardiac arrest and 58% had symptomatic VT. All patients had antiarrhythmic agents stopped 5 half-lives before evaluation and then had autonomic profile (upright tilt, cold pressor test, exercise testing and hand grip) as well as programmed electrical stimulation studies performed. Autonomic profile testing induced VT in 5 of 26 patients (19%) and in only 1 patient was the arrhythmia reproducibly induced. All 26 patients had VT induced on electrophysiologic testing; 9 patients had nonsustained and 17 had sustained VT. Lorcainide administered intravenously prevented VT induction in 20 of 26 patients tested, whereas procainamide was effective in 11 of 24 patients. Ten of the 13 not protected by procainamide were protected by lorcainide. Twenty patients were started on long-term lorcainide therapy and followed up for 29 +/- 3.4 months. Five patients have discontinued therapy, 2 because of breakthrough arrhythmias, 2 because of severe sleep-wake disturbances and 1 because of private physician preference. An additional 3 patients died during therapy because of myocardial infarction in 1, progressive myopathy in 1 and sudden death in 1. Sixty percent of patients started on lorcainide therapy have continued. In this patient population, noninvasive induction of VT is not a sensitive or reproducible technique in assessing antiarrhythmic therapy. Furthermore, when selected on the basis of electrophysiologic testing, lorcainide is a well-tolerated and effective antiarrhythmic agent.

Topics: Aged; Anti-Arrhythmia Agents; Benzeneacetamides; Dose-Response Relationship, Drug; Drug Evaluation; Electric Stimulation; Electrophysiology; Exercise Test; Female; Heart Arrest; Hemodynamics; Humans; Male; Middle Aged; Piperidines; Procainamide; Syncope; Tachycardia

Fourteen infants presenting with unexplained episodes of weakness or fainting were investigated by repeated Holter monitor recordings and oculocardiac reflexes (OCR). The recordings were then compared with those of 10 normal children in order to try to establish the criteria of vagal hyperreflexia. Results of OCR were collated with those of Holter: there was a good correlation between the length of the cardiac arrest on the OCR and the minimal instantaneous frequency and the maximal change of instantaneous frequency recorded on the Holter. The diagnostic difficulties of these vaso-vagal episodes in infants are emphasized. The potential gravity of these episodes and the possible relation with the sudden infant death syndrome are then discussed in the light of these cases.

Topics: Autonomic Nervous System Diseases; Child, Preschool; Electrocardiography; Female; Humans; Infant; Male; Parasympatholytics; Piperidines; Reflex, Oculocardiac; Syncope; Vagus Nerve

Topics: Adult; Aged; Ajmaline; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzeneacetamides; Electrocardiography; Female; Humans; Male; Middle Aged; Piperidines; Syncope; Time Factors