ABSTRACT
Ivabradine is a newly approved medication which reduces the heart rate by antagonizing the If channel. We report a case of intentional overdose on ivabradine. A 26-year-old female presented after taking 250 mg ivabradine. On arrival, her vital signs and neurologic exam were unremarkable. Within 30 min, her heart rate decreased to 31 bpm, but she remained normotensive with no change in mentation. Her bradycardia resolved after treatment with atropine. She experienced two further bradycardic episodes responsive to atropine; the second episode was associated with hypotension, responsive to a fluid bolus. For the remainder of her hospitalization, she remained hemodynamically stable without further interventions. She was dispositioned to the psychiatry service approximately 36 h post-ingestion with a heart rate of 67 bpm. Laboratory analysis confirmed a serum ivabradine concentration of 525 ng/mL, greater than 50 times the mean level in therapeutic trials. Proposed treatments for ivabradine include activated charcoal, atropine, isoproterenol, and intravenous pacing. Further study is needed to identify ideal treatment modalities.
Subject(s)
Anti-Arrhythmia Agents/poisoning , Benzazepines/poisoning , Cyclic Nucleotide-Gated Cation Channels/antagonists & inhibitors , Drug Overdose/physiopathology , Membrane Transport Modulators/poisoning , Adult , Anti-Arrhythmia Agents/blood , Anti-Arrhythmia Agents/therapeutic use , Atropine/therapeutic use , Benzazepines/blood , Benzazepines/therapeutic use , Bradycardia/etiology , Bradycardia/prevention & control , Combined Modality Therapy , Cyclic Nucleotide-Gated Cation Channels/metabolism , Drug Overdose/drug therapy , Drug Overdose/metabolism , Drug Overdose/therapy , Emergency Service, Hospital , Female , Humans , Ivabradine , Membrane Transport Modulators/blood , Membrane Transport Modulators/therapeutic use , Postural Orthostatic Tachycardia Syndrome/drug therapy , Suicide, Attempted , Treatment Outcome , VirginiaSubject(s)
Benzazepines/poisoning , Bradycardia/chemically induced , Drug Overdose/therapy , Suicide, Attempted , Adult , Antidotes/pharmacology , Antidotes/therapeutic use , Bradycardia/physiopathology , Calcium Gluconate/pharmacology , Calcium Gluconate/therapeutic use , Combined Modality Therapy , Drug Overdose/physiopathology , Electrocardiography , Female , Humans , Ivabradine , Loperamide/poisoning , Losartan/poisoning , Norepinephrine/therapeutic use , Pacemaker, Artificial , Poisoning/drug therapy , Poisoning/therapy , Spironolactone/poisoningABSTRACT
The smoking cessation agent varenicline acts as a partial agonist on α(4)ß(2) nicotinic acetylcholine receptors. Although debated, several reports have linked varenicline therapy to an increased risk of suicidal thoughts and/or suicide. In addition, several non-fatal overdose cases have been reported. In this report, we utilised a sample preparation procedure suitable for postmortem samples and gas chromatography coupled to mass spectrometry to analyse samples obtained from a suicidal case in which ingestion of an overdose of varenicline had occurred. Extremely high concentrations of varenicline (>250 ng/ml) were detected in the blood of the deceased, in addition to high concentrations in urine and vitreous humour. To the best of our knowledge, similar high concentrations have not been reported yet. Although, with respect to the mechanism of death in this case, confounding factors were concomitant ethanol consumption and, importantly, potentially fatal hypothermia, this is the first report of a fatality associated with the ingestion of an overdose of varenicline.
Subject(s)
Benzazepines/poisoning , Drug Overdose , Nicotinic Agonists/poisoning , Quinoxalines/poisoning , Suicide , Adult , Benzazepines/analysis , Central Nervous System Depressants/analysis , Ethanol/analysis , Forensic Toxicology , Gas Chromatography-Mass Spectrometry , Humans , Hypothermia/pathology , Male , Nicotinic Agonists/analysis , Quinoxalines/analysis , Varenicline , Vitreous Body/chemistryABSTRACT
BACKGROUND: Varenicline was approved by the Food and Drug Administration (FDA) as a prescription smoking cessation aid in May 2006. Varenicline is both a partial nicotine agonist and an antagonist. Recent reports by the Institute of Safe Medication Practices identified safety problems associated with varenicline use, and the FDA recently issued a boxed warning. These safety concerns regarding varenicline use prompted this study. OBJECTIVE: To characterize varenicline-exposed patients as reported to a poison control system. METHODS: We performed a retrospective search of the California Poison Control System electronic database from August 2006 through August 2008, using the term varenicline or Chantix. Cases matching these results were reviewed. All ages were included. Excluded were patients with coingestants and unknown outcomes. Clinical parameters and medical outcomes were extracted from the database. RESULTS: Thirty-six cases met inclusion criteria and 17 cases were excluded, Ten cases involved nonpediatric patients; 9 cases involved patients less than 6 years old, which were defined as pediatric patients. The median duration of poison center follow-up for pediatric patients was 253 minutes; median duration of follow-up for nonpediatric patients with unintentional exposures was 28.5 minutes. The majority of exposures were unintentional and included all the pediatric patients and 6 nonpediatric patients who had unintentional medication errors. Gastrointestinal and neuropsychiatric adverse events were most frequently reported. The majority of these patients were managed at home. Among those evaluated at a healthcare facility, only 1 pediatric patient was admitted. Of the remaining patients, 1 nonpediatric patient reported a deliberate exposure and 3 nonpediatric patients experienced adverse effects at therapeutic doses. Median duration of follow-up for these patients was 308 minutes. CONCLUSIONS: Patients exposed to varenicline in our study had favorable outcomes. Gastrointestinal and neuropsychiatric effects were the most commonly reported adverse events. A dose-response relationship could not be determined and triage criteria to a healthcare facility remain undetermined.
Subject(s)
Benzazepines/poisoning , Nicotinic Agonists/poisoning , Poison Control Centers/statistics & numerical data , Quinoxalines/poisoning , Adolescent , Adult , Benzazepines/administration & dosage , Child, Preschool , Databases, Factual , Female , Follow-Up Studies , Gastrointestinal Diseases/chemically induced , Humans , Infant , Male , Medication Errors , Mental Disorders/chemically induced , Nicotinic Agonists/administration & dosage , Quinoxalines/administration & dosage , Retrospective Studies , Smoking Cessation/methods , VareniclineABSTRACT
HISTORY AND CLINICAL FINDINGS: A 78-year-old woman was admitted to the intensive care unit 9 hours after ingestion of 2 g of isosorbitmononitrate, 430 mg of amlodipine, 250 mg of benazepril and 600 mg of mirtazapin in suicidal intent. INVESTIGATIONS: Clinical findings and invasive monitoring showed signs of a hyperdynamic hemodynamic cardiovascular failure caused by toxic vasodilatation. TREATMENT AND COURSE: Despite of primary detoxication, intravenous volume infusion with calcium gluconate, glucagon and naloxone and administration (norepinephrine up to 2 micro g/kg/min) no hemodynamic stabilization was achieved. Only when the vasopressin-analogue argipressin was given peripheral vasodilatation was overcome and hemodynamic stabilization resulted. 10 hours after discontinuing argipressin and norepinephrine the patient developed a mesenteric ischemia, and she finally died on the third day after admission. CONCLUSION: In circulatory shock due to toxic vasodilatation the use of vasopressin analogue argipressin can be helpful as an ultima therapeutic measure in catecholamine refractory shock caused by vasodilatation. Attention must be paid to overwhelming vasoconstrictor effects resulting in mesenteric ischemia.
Subject(s)
Arginine Vasopressin/administration & dosage , Isosorbide Dinitrate/analogs & derivatives , Mianserin/analogs & derivatives , Poisoning/drug therapy , Suicide, Attempted , Vasoconstrictor Agents/administration & dosage , Vasodilator Agents/poisoning , Adrenergic alpha-Antagonists/administration & dosage , Adrenergic alpha-Antagonists/poisoning , Aged , Amlodipine/administration & dosage , Amlodipine/poisoning , Angiography , Angiotensin-Converting Enzyme Inhibitors/administration & dosage , Angiotensin-Converting Enzyme Inhibitors/poisoning , Arginine Vasopressin/therapeutic use , Benzazepines/administration & dosage , Benzazepines/poisoning , Female , Heart Rate , Hemodynamics , Humans , Infusions, Intravenous , Injections, Intravenous , Isosorbide Dinitrate/administration & dosage , Isosorbide Dinitrate/poisoning , Mesenteric Arteries/diagnostic imaging , Mianserin/administration & dosage , Mianserin/poisoning , Mirtazapine , Poisoning/mortality , Poisoning/physiopathology , Time Factors , Vasoconstrictor Agents/therapeutic use , Vasodilator Agents/administration & dosageABSTRACT
A 74-year-old man presented with bradycardia, diaphoresis, mental confusion, and slurred speech. He developed asystole and was managed successfully with temporary emergency transvenous pacing and support of ventilation and blood pressure. He later was found to have ingested approximately 1,500 mg diltiazem, apparently as the result of an error created by his blindness and chronic confusion.
Subject(s)
Benzazepines/poisoning , Diltiazem/poisoning , Heart Arrest/chemically induced , Aged , Heart Arrest/therapy , Humans , Male , Medication Errors , ResuscitationSubject(s)
Benzazepines/poisoning , Diltiazem/poisoning , Diltiazem/metabolism , Humans , Kinetics , Male , Middle Aged , Suicide, AttemptedSubject(s)
Benzazepines/poisoning , Diltiazem/poisoning , Heart Block/chemically induced , Aged , Humans , Male , Suicide, AttemptedSubject(s)
Benzazepines/therapeutic use , Affective Symptoms/drug therapy , Alcoholism/drug therapy , Analgesia , Anesthesia, General , Anesthesia, Obstetrical , Anti-Anxiety Agents/therapeutic use , Anxiety/drug therapy , Benzazepines/adverse effects , Benzazepines/pharmacology , Benzazepines/poisoning , Chlordiazepoxide/therapeutic use , Diazepam/administration & dosage , Diazepam/adverse effects , Diazepam/therapeutic use , Electric Countershock , Endoscopy , Enzyme Induction/drug effects , Female , Humans , Injections, Intravenous/adverse effects , Neurologic Manifestations , Neuromuscular Diseases/drug therapy , Nitrazepam/therapeutic use , Preanesthetic Medication , Pregnancy , Psychoses, Substance-Induced/etiology , Seizures/drug therapy , Sleep Wake Disorders/drug therapy , Substance Withdrawal Syndrome/drug therapy , Substance-Related DisordersSubject(s)
Barbiturates/poisoning , Hypnotics and Sedatives/poisoning , Benzazepines/poisoning , Blood Pressure , Blood Transfusion , Diuresis , Glutethimide/poisoning , Humans , Intensive Care Units , Metaraminol/therapeutic use , Methaqualone/poisoning , Norepinephrine/therapeutic use , Peritoneal Dialysis , Phenothiazines/poisoning , Poisoning/therapy , Renal Dialysis , Respiration, Artificial , Shock/chemically induced , Shock/therapySubject(s)
Anticonvulsants/therapeutic use , Benzazepines/therapeutic use , Epilepsy/drug therapy , Administration, Oral , Adolescent , Adult , Anticonvulsants/administration & dosage , Anticonvulsants/adverse effects , Anticonvulsants/poisoning , Benzazepines/administration & dosage , Benzazepines/adverse effects , Benzazepines/poisoning , Child , Child Behavior Disorders/chemically induced , Child, Preschool , Electroencephalography , Epilepsy, Absence/drug therapy , Epilepsy, Temporal Lobe/drug therapy , Epilepsy, Tonic-Clonic/drug therapy , Female , Humans , Injections, Intravenous , Ketones/therapeutic use , Male , Nitro Compounds/therapeutic use , Sleep/drug effectsSubject(s)
Benzazepines/analysis , Forensic Medicine , Animals , Benzazepines/poisoning , Cadaver , Chromatography , Humans , Kidney/analysis , Liver/analysis , Spectrum Analysis , Stomach/analysisSubject(s)
Benzazepines/poisoning , Blister/chemically induced , Adult , Coma/chemically induced , Female , HumansSubject(s)
Benzazepines/urine , Administration, Oral , Animals , Benzazepines/metabolism , Benzazepines/poisoning , Colorimetry , Humans , Hypnotics and Sedatives/urine , Male , RabbitsSubject(s)
Hypoxia, Brain/complications , Myoclonus/etiology , Stereotaxic Techniques , Thalamic Nuclei/surgery , Adult , Benzazepines/poisoning , Cerebral Cortex/physiopathology , Coma/complications , Electric Stimulation , Electroencephalography , Electromyography , Female , Humans , Myoclonus/surgery , Thalamic Nuclei/physiopathologyABSTRACT
Though recovery of consciousness after drug overdose may occur within a day or two, the drug itself may not finally leave the brain for another one to three weeks, and at this late time a withdrawal syndrome can occur, with insomnia, restlessness, raised paradoxical (R.E.M.) sleep, epileptic phenomena, and even delirium. It is proposed that a high degree of drug-tolerance and dependence can be rapidly acquired after overdose.Abnormal sleep features of 10 patients resolved only slowly over a period of up to two months after overdose. The data support the view that R.E.M. sleep is concerned with processes of brain repair.