cardiovascular-agents and Drug-Overdose

Calcium channel blockers continue to be used for the management of a wide variety of adult and pediatric conditions including hypertension, angina pectoris, atrial arrhythmias, Raynaud phenomenon, and migraine headaches. With increased use comes increased potential for misuse and abuse. This article serves as a review of calcium channel blocker physiology with emphasis on presentation and management of the pediatric patient with calcium channel blocker toxicity.

Topics: Adult; Assisted Circulation; Calcium Channel Blockers; Calcium Channels, L-Type; Calcium Chloride; Cardiovascular Agents; Cardiovascular Diseases; Charcoal; Child, Preschool; Combined Modality Therapy; Drug Overdose; Enema; Extracorporeal Circulation; Fat Emulsions, Intravenous; Fluid Therapy; Glucagon; Heart; Humans; Hyperglycemia; Infant; Muscle, Smooth, Vascular; Plasmapheresis; Poisoning; Practice Guidelines as Topic

This report describes two patients who were victims of massive verapamil ingestion and then reviews the available literature. Because verapamil blocks the slow calcium channels of the heart and blood vessels, the use of calcium as a treatment would be logical. In the two cases reported here, calcium was only transiently effective in maintaining cardiac output and blood pressure. Several other agents were then used and most were ineffective. This is similar to experience reported in the literature that suggests that no single agent is capable of reversing verapamil's negative inotropic, dromotropic, chronotropic, and vascular smooth muscle effects.

Topics: Adrenergic alpha-Agonists; Adult; Calcium; Cardiovascular Agents; Drug Overdose; Female; Glucagon; Humans; Male; Verapamil

Ivabradine is a bradycardic drug used worldwide in the treatment of chronic stable angina and chronic heart failure. We presented here a case of a 61-year-old woman who was admitted to emergency department for overdose. She presented with drowsiness, bradycardia (45bpm) and a low blood pressure (116/21mmHg). She died ten hours after admission from multiple organ failure. Ivabradine was quantified in different matrices sampled during autopsy using a method on LC-MS/MS (TSQ Vantage Thermo Fisher Scientific®), after a double liquid-liquid extraction with a mixture of hexane/ethyl acetate (1/1; v/v) and then chloroform/isopropanol (80/20; v/v). Chromatographic separation was achieved using a Hypersyl gold PFP column (200×2.1mm, 1.9μm) and an acetonitrile/formiate 2mM, 0.1% formic acid buffer gradient. Method was fully validated on whole blood. The mean overall recovery was 90%. Linearity was validated in the 5-500ng/mL range, with intra and inter-day precision lower than 14.3%. The ivabradine concentration found in patient post-mortem blood was 1210ng/mL. Ivabradine was also quantified in different viscera like lung (2910ng/g), kidney (1510ng/g), liver (1050ng/g), heart (900ng/g), and brain (110ng/g). The vitreous humor concentration was 760ng/mL. Pregabalin and zopiclone were also found in blood at 50μg/mL and 206ng/mL, respectively. This case seems to be the first report of a fatal intoxication involving ivabradine and the first published concentrations in organs.

Topics: Brain Chemistry; Cardiovascular Agents; Chromatography, Liquid; Drug Overdose; Female; Forensic Toxicology; Humans; Ivabradine; Kidney; Liver; Lung; Middle Aged; Myocardium; Tandem Mass Spectrometry; Vitreous Body

We describe a 27-year-old female with repeated episodes of pulseless electrical activity due to intoxication with a substance that was unidentified at presentation. Severe QRS widening was observed and empiric treatment with sodium bicarbonate and intravenous lipid emulsion was administered. In this case, intraosseous administration of lipid emulsion failed to improve haemodynamic parameters, suggesting that this dose remained in the bone marrow compartment. We recommend that physicians become aware of this possibility and to avoid intraosseous administration of lipid emulsion.

Topics: Adult; Antimalarials; Buffers; Calcium Gluconate; Cardiovascular Agents; Chloroquine; Critical Care; Drug Overdose; Electrocardiography; Fat Emulsions, Intravenous; Female; Heart Arrest; Humans; Infusions, Intraosseous; Sodium Bicarbonate; Suicide, Attempted; Treatment Outcome

Adults aged >65 years are susceptible to intentional and unintentional poisoning, with contributing factors that include polypharmacy, comorbidity, susceptibility to medication error, and gaps in research. Although toxicologists are often tasked with managing and preventing poisoning among older adults, little is known about sex differences in these poisonings. The aim of this study was to review sex differences in poisonings among older adults managed at the bedside by medical toxicologists.. All case subjects aged >65 years in the Toxicology Investigators Consortium (ToxIC) registry between January 2010 and December 2016 were reviewed. Data included reasons for exposure and consultation, exposure agents and routes, presenting clinical findings, and treatment provided. Cases missing age, sex, or primary reason for toxicology consultation data were excluded. We used χ. Among 51,441 total registry cases, 542 (1.05%) were excluded because of missing data. Among the remaining 50,899 cases, 2930 (5.8%) were included for age >65 years; 52.3% of older adults were female. Race was missing or unknown for 49.2% of cases. Adverse drug reactions were more commonly encountered in female subjects than in their male counterparts (9.6% vs 6.4%; P = 0.001). No statistically significant sex differences were observed for total numbers of intentional, unintentional pharmaceutical, and nonpharmaceutical exposures. The most common medications involved were cardiovascular (16.8%) and analgesics/opioids (14.8%). Female subjects were more likely than male subjects to be evaluated by a toxicologist for cardiovascular medications (18.7% vs 14.7%; P = 0.004) and analgesics/opioids (17.6% vs 11.8%; P < 0.001). Male subjects were more likely than female subjects to be evaluated for ethanol toxicity (7.4% vs 1%; P < 0.001) and for envenomations (4.2% vs 1.8%; P < 0.001). The most common route of exposure was oral ingestion (81.3%). Signs/symptoms were noted in 54.8% of cases, with the most common abnormal vital sign being bradycardia (17.2%). Pharmacologic support was the most common intervention and was more common in male subjects than in female subjects (17.7% vs 12.3%; P < 0.001). Deaths were reported in 38 female subjects (2.45%) and 46 male subjects (3.34%); there was no statistically significant difference in death rate according to sex (P = 0.148).. Older female adults were more commonly evaluated by a medical toxicologist for an adverse drug reaction than older male adults. Female patients were more likely than male patients to be evaluated for poisoning related to analgesic/opioids and cardiovascular medications, and older male patients more frequently received pharmacologic support than older female patients. No significant sex differences were observed in numbers of toxicology consultations for intentional, unintentional pharmaceutical, and nonpharmaceutical exposures.

Topics: Aged; Analgesics, Opioid; Bites and Stings; Cardiovascular Agents; Drug Overdose; Drug-Related Side Effects and Adverse Reactions; Ethanol; Female; Humans; Male; Medication Errors; Poisoning; Polypharmacy; Registries; Sex Factors; United States

We hypothesized that in chronic digoxin toxicity, anti-digoxin antibodies (Fab) would be efficacious in binding digoxin, but this may not translate into improved clinical outcomes.. This study aims to investigate changes in free digoxin concentrations and clinical effects on heart rate and potassium concentrations in chronic digoxin poisoning when anti-digoxin Fab are given.. This is a prospective observational study. Patients were recruited if they have been treated with anti-digoxin Fab for chronic digoxin poisoning. Data was entered into a standardised prospective form, supplemented with medical records. Their serum or plasma was collected, analysed for free and bound digoxin and free anti-digoxin Fab concentrations.. From September 2013 to February 2015, 36 patients (median age, 78 years; 22 females) were recruited from 18 hospitals. Median heart rate (HR) was 49 beats/min. Initial median digoxin and potassium concentrations were 4.7 nmol/L (3.6 μg/L) (range: 2.3-11.2 nmol/L) and 5.3 mmol/L (range: 2.9-9.2 mmol/L) respectively. Beta-blockers (n = 18), calcium antagonists (n = 6), spironolactone and/or angiotensin blocking agents (n = 24) were also used concomitantly. Renal impairment and gastrointestinal symptoms were present in 31 (86%) and 22 (63%) patients respectively. Five patients died from conditions unrelated to digoxin toxicity. Median change in HR was 8 beats/min post-Fab with no effect on blood pressure; they were 4, 10 and 17 beats/min for the 1, 2 and ≥3 vials of anti-digoxin Fab groups respectively. Concomitant treatments with potassium lowering agents (12/36) and inotropic drugs (7/36) were used. Gastrointestinal effects resolved in all 22 patients. The median decrease for potassium was 0.3 mmol/L. Digoxin concentration reduced from 3.8 to 0 nmol/L post-Fab. There was a rebound observed in the free digoxin concentration in 25 patients but none had associated clinical deterioration.. One to two vials of anti-digoxin Fab initially bound all free digoxin confirming Fab efficacy. However, this was associated with only a moderate improvement in HR and potassium, suggesting bradyarrhythmia and hyperkalaemia may be from other co-morbidities.

Topics: Aged; Aged, 80 and over; Bradycardia; Cardiovascular Agents; Chronic Disease; Digoxin; Drug Overdose; Female; Heart Rate; Humans; Hyperkalemia; Immunoglobulin Fab Fragments; Male; Middle Aged; Poisoning; Potassium; Prospective Studies

Overdose of cardiovascular medications is increasingly associated with morbidity and mortality. We present a case of substantial atenolol, chlorthalidone, and lisinopril overdose treated by multiple modalities with an excellent outcome.. Aggressive medical intervention did not provide sufficient hemodynamic stability in this patient with refractory cardiogenic and distributive shock. Impella® percutaneous left ventricular assist device and extracorporeal membrane oxygenation provided support while the effects of the overdose subsided. We present concentrations demonstrating removal of atenolol with continuous venovenous hemodiafiltration. This is the first report of esophagogastroduo denoscopy decontamination of this overdose with a large pill fragment burden.

Topics: Adrenergic beta-1 Receptor Antagonists; Adult; Atenolol; Cardiovascular Agents; Chlorthalidone; Combined Modality Therapy; Decontamination; Drug Overdose; Emergency Service, Hospital; Endoscopy, Digestive System; Extracorporeal Membrane Oxygenation; Female; Humans; Lisinopril; Multiple Organ Failure; Renal Dialysis; Shock, Cardiogenic; Tablets; Transcutaneous Electric Nerve Stimulation; Treatment Outcome

Ranolazine is a new anti-anginal medication that was approved by the US Food and Drug Administration (FDA) in 2006 for patients with symptomatic chronic angina despite optimized therapy. This paper presents a case report of a fifteen year old male patient admitted to the pediatric intensive care unit after ranolazine overdose ingestion. He had recurrent new onset seizures that are most likely due to ranolazine overdose. Seizures have never been reported with ranolazine use or abuse.

Topics: Adolescent; Cardiovascular Agents; Drug Overdose; Glasgow Coma Scale; Humans; Male; Ranolazine; Seizures; Suicide, Attempted

Topics: Cardiovascular Agents; Drug Overdose; Fat Emulsions, Intravenous; Humans; Propranolol

Topics: Adult; Cardiovascular Agents; Drug Overdose; Electrocardiography; Fat Emulsions, Intravenous; Female; Humans; Propranolol

Topics: Animals; Antidotes; Cardiotonic Agents; Cardiovascular Agents; Disease Models, Animal; Drug Overdose; Hemodynamics; Hydrazones; Phosphodiesterase Inhibitors; Pyridazines; Rats; Severity of Illness Index; Simendan; Vasodilator Agents; Verapamil

Perhexiline is a prophylactic anti-anginal agent that ameliorates the metabolic basis for myocardial ischaemia and is increasingly used in the management of acute coronary syndromes. No intravenous preparation is available and usual oral loading regimens require 2-3 days to achieve therapeutic drug levels. Two patients presenting to hospital with single-dose over-dosage of perhexiline (6500 mg and 1000 mg, respectively) provided a basis for examining the safety of large single dosage of perhexiline and associated time-course of drug levels. Neither patient had previously taken perhexiline. Peak plasma perhexiline concentrations occurred within 12 h of ingestion and were 2.58 and 0.50 mg/L, respectively (therapeutic range 0.15-0.60 mg/L). The first patient developed transient nausea and vomiting; the second patient had no adverse effects. Subsequently, a series of 10 patients with acute coronary syndromes received an 800-mg loading dose. Peak concentrations occurred within 12 h postdose; the mean levels achieved were 0.40 +/- 0.16 mg/L (standard error of the mean). No serious adverse effects were seen. Two patients reported transient nausea or vomiting within 24 h of the loading dose. The utility of this rapid loading regimen for incremental suppression of myocardial ischaemia remains to be assessed.

Topics: Adult; Cardiovascular Agents; Coronary Disease; Drug Administration Schedule; Drug Overdose; Female; Humans; Male; Middle Aged; Perhexiline; Self Medication

Topics: Arrhythmias, Cardiac; Cardiovascular Agents; Diazepam; Drug Overdose; Female; Humans; Hydroxychloroquine; Hypokalemia; Hypotension

Topics: Angina Pectoris; Calcium Channel Blockers; Cardiovascular Agents; Diltiazem; Drug Overdose; Humans; Male; Middle Aged

Topics: Adult; Anuria; Bradycardia; Cardiovascular Agents; Cold Temperature; Coma; Combined Modality Therapy; Drug Overdose; Electric Countershock; Emergencies; Extracorporeal Membrane Oxygenation; Female; Frostbite; Humans; Hypotension; Hypothermia; Intermittent Positive-Pressure Ventilation; Psychotropic Drugs; Resuscitation; Suicide, Attempted; Ventricular Fibrillation

Priapism is a urologic disorder and medical emergency with a variety of known etiologies including the use of psychotropic medications. The antidepressant trazodone is the agent most frequently implicated in the precipitation of priapism. Additionally, a number of drugs of abuse including marijuana, ethanol, and cocaine have been known to cause the disorder. It is unknown if drugs may act in an additive or a synergistic manner to cause priapism. We report a case of priapism which occurred following trazodone overdose in an individual actively using cocaine. This case suggests that combined trazodone and cocaine use may pose an additional risk of priapism. Since trazodone is commonly employed as a hypnotic and often chosen for polysubstance abusers due to its low abuse potential, clinicians should be aware of the possible additive risk of priapism in this patient population.

Topics: Adult; Cardiovascular Agents; Cocaine; Cocaine-Related Disorders; Drug Interactions; Drug Overdose; Humans; Male; Narcotics; Priapism; Selective Serotonin Reuptake Inhibitors; Suicide, Attempted; Trazodone

Intravenous diltiazem has become a preferred medication for treating supraventricular tachyarrhythmias in hospitalized patients. We present a case of inadvertent acute overdosage, its clinical effects, and successful treatment using intravenous glucagon.

Topics: Acute Disease; Aged; Cardiovascular Agents; Diltiazem; Drug Overdose; Female; Glucagon; Humans; Infusions, Intravenous; Injections, Intravenous