[Diagnostics and treatment of selected clinically relevant, acute drug intoxications]. / Diagnostik und Behandlung ausgesuchter akuter Arzneimittelvergiftungen mit hoher klinischer Relevanz.

Acute drug poisoning due to accidental or self-damaging overdoses is responsible for 5-10% of emergency medical interventions in Germany. The treatment of asymptomatic to life-threatening courses requires extensive expertise. On the basis of a selective literature search, this article gives an overview of selected clinically relevant, acute drug poisonings with regard to epidemiology, symptomatology, diagnostics, and therapy.Intoxications with psychotropic drugs are the most common drug intoxications. Poisoning with tricyclic antidepressants causes anticholinergic, central nervous, and cardiovascular symptoms. Less toxic are selective serotonin reuptake inhibitors (SSRIs); the intoxication may be characterized by serotonin syndrome. Malignant neuroleptic syndrome is a severe complication of neuroleptic poisoning.Poisoning with analgesics is clinically relevant due to its high availability. For paracetamol poisoning, intravenous acetylcysteine is available as an antidote. Hemodialysis may be indicated for severe salicylate intoxication. Poisoning with nonsteroidal anti-inflammatory drugs is usually only associated with mild signs of intoxication.Poisoning with cardiac drugs (ß-blockers and calcium antagonists) can cause life-threatening cardiovascular events. In addition to symptomatic therapy, insulin glucose therapy also plays an important role.The majority of acute drug poisonings can be treated adequately by symptomatic and partly intensive care therapy - if necessary with the application of primary and secondary toxin elimination. Depending on the severity of the intoxication, pharmacology-specific therapy must be initiated.

Suicidal bupropion ingestions in adolescents: increased morbidity compared with other antidepressants.

OBJECTIVE: Bupropion is often categorized as a newer generation antidepressant and assessed with serotonin reuptake inhibitors as a lower risk than older tricyclic antidepressants (TCAs). The objective of this study was to compare outcomes in adolescent suicide from ingestions between bupropion and TCA medications. STUDY DESIGN: An analysis of the National Poison Data System for exposures coded "suspected suicide" in adolescents (age: 13-19) was undertaken for the years 2013-2016 and included TCAs or bupropion. We compared clinical effects, therapies and medical outcomes. RESULTS: Over the four-year period there were 2253 bupropion and 1496 TCA adolescent suspected suicide calls. There was a significant linear increase in bupropion ingestions over the four years. Across all years, there were on average 189.2 (95% CI: 58.1-320.4; p = .01) more ingestions of bupropion than TCA. When comparing bupropion to a TCA, ingestions of bupropion were significantly more likely to be accompanied by seizure (30.7% vs 3.9%; p < .01), to be admitted (74.8% vs 61.6%; p < .01) and medical outcomes to be coded as a major outcome (19.3% vs 10.0%; p < .01). The number of cases with death or major clinical outcome for both increased over the four-year period. Ingestions of bupropion were less likely to have hypotension (2.7% vs 8.0%; p < .01) and less likely to be intubated (5.6% vs 16.4%; p < .01) as compared to ingestions of TCA. CONCLUSIONS: Adolescents who overdose on a single medication in a suicide attempt with bupropion have a statistically significant higher incidence of major outcomes and seizures. The risks of bupropion as a potential means of suicidal gesture by overdose must be considered, and weighed against its benefits and side effect profile when choosing an appropriate agent for the treatment of depression in adolescents.

Amitriptyline-induced ventricular tachycardia: a case report.

BACKGROUND: In Bangladesh, each emergency physician faces amitriptyline overdose nearly a day. An acute cardiovascular complication, one of the worst complications is mainly responsible for the mortality in tricyclic overdose. Recently, we managed ventricular tachycardia in a young female presented with an impaired consciousness 10 h after intentionally ingesting 2500 mg amitriptyline. Here, we report it, discuss how the electrocardiography is vital to acknowledge and predict it and its' complications and also the recent update of the management of it. CASE PRESENTATION: A young married Bangladeshi-Bengali girl, 25-year-old, having a history of disharmony with her husband, came with an impaired consciousness after intentionally ingesting 2500 mg amitriptyline about 10 h before arrival. There was blood pressure 140/80 mmHg, heart rate 140 beats-per-min, temperature 103 °F, Glasgow coma scale 10/15, wide complex tachycardia with QRS duration of 178 ms in electrocardiography, blood pH 7.36. Initially, treated with 100 ml 8.4% sodium bicarbonate. After that, QRS duration came to 100 ms in electrocardiography within 10 min of infusion. To maintain the pH 7.50-7.55 over the next 24 h, the infusion of 8.4% sodium bicarbonate consisting of 125 ml dissolved in 375 ml normal saline was started and titrated according to the arterial blood gas analysis. Hence, a total dose of 600 mmol sodium bicarbonate was given over next 24 h. In addition to this, gave a 500 ml intravenous lipid emulsion over 2 h after 24 h of admission as she did not regain her consciousness completely. Afterward, she became conscious, though, in electrocardiography, ST/T wave abnormality persisted. So that, we tapered sodium bicarbonate infusion slowly and stopped it later. At the time of discharge, she was by heart rate 124/min, QRS duration 90 ms in electrocardiogram along with other normal vital signs. CONCLUSION: Diagnosis of amitriptyline-induced ventricular tachycardia is difficult when there is no history of an overdose obtained. Nevertheless, it should be performed in the clinical background and classic electrocardiographic changes and wise utilization of sodium bicarbonate, intravenous lipid emulsion, and anti-arrhythmic drugs may save a life.

Suicidal overdose with relapsing clomipramine concentrations due to a large gastric pharmacobezoar.

The paper presents a case of fatal intoxication after massive sustained-release clomipramine overdosage with prolonged toxicity related to a large gastric pharmacobezoar. 42-year-old female was admitted to the toxicology unit 14 h after drugs ingestion. At admission patient was deeply unconscious, required controlled mechanical ventilation. Serum total level of TCAs was 1955 ng/mL. Gastric lavage revealed no pills. Within the next 12h the patient's clinical condition improved. TCAs level decreased to 999 ng/mL. However, after another 10h the clinical condition started deteriorating again and the patient went into a deep coma requiring controlled mechanical ventilation. TCAs level increased to 2011 ng/mL. X-ray and computed tomography revealed large pharmacobezoar consisted from radio-opaque pills. In the 28th h of hospitalization gastrotomy was performed, confirming presence of pharmacobezoar formed from Anafranil SR tablets. After surgery TCAs level was gradually decreasing. However, the patient's condition did not improve, she died 32 h after gastrotomy. Post-mortem analyses revealed drug and its metabolite toxic levels in blood (clomipramine - 1729 ng/mL, norclomipramine - 431 ng/mL) and toxic levels in internal organs: myocardium (clomipramine - 14,420 ng/g, norclomipramine - 35,930 ng/g), vitreous humor (clomipramine - 1000 ng/mL, norclomipramine - 3110 ng/mL). Described case report indicates that sustained release clomipramine tablets may form pharmacobezoar. X-ray and computed tomography examinations should be considered in cases of massive abuse of sustained release clomipramine, particularly if symptoms of intoxication are recurrent or persistent.

Intoxicación por antidepresivos tricíclicos en pediatría: aproximación y manejo / Pediatric Tricyclic Antidepressant Poisoning: Approach and Management

Los antidepresivos son agentes que causan una importante morbilidad y mortalidadcon presentación de un espectro de toxicidad único, principalmente cardiovasculary neurológico, el cual se basa principalmente en su farmacología y que determina sutratamiento específico. Por desgracia, los niños son una población vulnerable, y con elaumento de patologías psiquiátricas que son tratadas con este tipo de medicamentos,cada vez es más probable encontrar toxicidad en esta población. El propósito de estapublicación es revisar la farmacocinética, la presentación clínica y el tratamiento de laintoxicación aguda por antidepresivos tricíclicos...

Antidepressants are agents that cause significant morbidity and mortality with importanttoxicity particularly on cardiovascular and neurological systems, which is mainly basedon their pharmacology and is that determines specific treatment. Unfortunately, childrenare vulnerable population because the increase in psychiatric disorders which are treatedwith these drugs. The purpose of this article is to review the pharmacokinetics, clinicalpresentation and treatment of acute poisoning with tricyclic antidepressants...

Rhabdomyolysis as a manifestation of clomipramine poisoning / Rabdomiolise como manifestacao de intoxicacao por clomipramina

CONTEXT: Tricyclic antidepressive agents are widely used in suicide attempts and present a variety of deleterious effects. Rhabdomyolysis is a rare complication of such poisoning. CASE REPORT: A 55-year-old woman ingested 120 pills of 25 mg clomipramine in a suicide attempt two days before admission. After gastric lavage in another emergency department on the day of intake, 80 pills were removed. On admission to our department, she was disoriented, complaining of a dry mouth and tremors at the extremities. An electrocardiogram showed a sinus rhythm with narrow QRS complexes. Laboratory results showed high creatine phosphokinase (CK = 15,094 U/l on admission; normal range = 26 to 140 U/l), hypocalcemia, slightly increased serum transaminases and mild metabolic acidosis. The patient's medical history included depression with previous suicide attempts, obsessive-compulsive disorder, hypothyroidism and osteoporosis. She presented cardiac arrest with pulseless electric activity for seven minutes and afterwards, without sedation, showed continuous side-to-side eye movement. She developed refractory hypotension, with need for vasopressors. Ceftriaxone and clindamycin administration was started because of a hypothesis of bronchoaspiration. The patient remained unresponsive even without sedation, with continuous side-to-side eye movement and a decerebrate posture. She died two months later. Rhabdomyolysis is a very rare complication of poisoning due to tricyclic drugs. It had only previously been described after an overdose of cyclobenzaprine, which has a toxicity profile similar to tricyclic drugs. CONCLUSIONS: Although arrhythmia is the most important complication, rhabdomyolysis should be investigated in cases of clomipramine poisoning. .

CONTEXTO: Antidepressivos tricíclicos são amplamente utilizados em tentativas de suicídio e apresentam diversos efeitos deletérios, sendo a rabdomiólise uma complicação rara dessa intoxicação. RELATO DO CASO: Uma mulher de 55 anos ingeriu 120 comprimidos de clomipramina de 25 mg numa tentativa de suicídio dois dias antes da admissão. Após lavagem gástrica em outro serviço de urgência no dia da ingestão, 80 comprimidos foram retirados. Na admissão em nosso serviço, a paciente estava desorientada, queixando-se de boca seca e tremores de extremidades. O eletrocardiograma mostrou ritmo sinusal com complexos QRS estreitos. Exames laboratoriais evidenciaram aumento de creatinofosfoquinase (CK = 15.094 U/L na admissão; intervalo da normalidade = 26 a 140 U/L), hipocalcemia, discreto aumento das transaminases e leve acidose metabólica. Antecedentes pessoais incluíam depressão com tentativas de suicídio prévias, transtorno obsessivo compulsivo, hipotireoidismo e osteoporose. A paciente apresentou parada cardiorrespiratória com atividade elétrica sem pulso por sete minutos e, posteriormente, sem sedação, foi observado olhar em varredura. A paciente evoluiu com hipotensão refratária, necessitando de vasopressores. Ceftriaxone e clindamicina foram iniciados pela hipótese de broncoaspiração. A paciente permaneceu irresponsiva mesmo sem sedação, com olhar em varredura contínuo e postura descerebrada. A paciente evoluiu para óbito dois meses após. Rabdomiólise é uma complicação rara da intoxicação por tricíclicos, e só foi descrita em overdose de ciclobenzaprina, a qual tem um perfil de toxicidade semelhante aos tricíclicos. CONCLUSÕES: Apesar de as arritmias serem as complicações mais temidas, ...

Adenosine-mediated cardiovascular toxicity in amitriptyline-poisoned rats.

We investigated the contribution of endogenous adenosine to amitriptyline-induced cardiovascular toxicity in rats. A control group of rats was pretreated with intraperitoneal (i.p.) 5% dextrose and received intravenous 0.94 mg/kg/min of amitriptyline for 60 minutes. The second and third groups of rats pretreated with i.p. 10 mg/kg of erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA), an adenosine deaminase inhibitor, and i.p. 1 mg/kg of S-(4-nitrobenzyl)-6-thioinosine (NBTI), a facilitated adenosine transport inhibitor, received 5% dextrose and amitriptyline infusion, respectively. Outcome parameters were mean arterial pressure (MAP), heart rate (HR), QT and QRS durations, and plasma adenosine concentrations. Plasma adenosine concentrations were increased in all groups. In the control group, amitriptyline decreased MAP and HR and prolonged QT and QRS durations after 10 minutes of infusion. In EHNA/NBTI-pretreated rats, amitriptyline prolonged QRS duration at 10 and 20 minutes. In EHNA/NBTI pretreated rats, amitriptyline-induced MAP, HR reductions, and QRS prolongations were more significant than that of dextrose-infusion-induced changes. Our results indicate that amitriptyline augmented the cardiovascular effects of endogen adenosine by increasing plasma levels of adenosine in rats.

Effects of adenosine receptor antagonists on survival in amitriptyline-poisoned mice.

OBJECTIVE: We investigated the effects of adenosine receptor antagonists on survival rates in a mouse model of amitriptyline poisoning. MATERIALS AND METHODS: In the preliminary study, amitriptyline was given at doses of 75, 100, and 125 mg/ kg to mice intraperitoneally (i.p.; n = 20 for each dose) to determine the lethal dose at 50% (LD(50)). Different doses (1, 3, and 5 mg/kg) of DPCPX (selective adenosine A(1) antagonists, n = 10 for each dose, total n = 30) or CSC (selective adenosine A(2a) antagonists, n = 10 for each dose, total n = 30) were given i.p. to find the nonlethal dose. After the administration of the LD(50) dose of amitriptyline (125 mg/kg), mice were treated with DPCPX (3 mg/kg), CSC (3 mg/kg), saline, or DMSO (dimethyl sulfoxide) (n = 25 for each group). Mice were observed during a 24-hour period. RESULTS: Kaplan-Meier estimates of the 24-hour survival rate was 52% (13/25) for saline and 68% (17/25), 52% (13/25), and 40% (10/25) for the DPCPX, CSC, and DMSO groups, respectively. There was no statistically significant difference in survival rates among the groups (P > 0.05). CONCLUSIONS: Adenosine antagonists failed to increase the survival rates of amitriptyline-poisoned mice. Further studies are needed with repeated doses of adenosine antagonists.

Accidental ingestion of dosulepin presenting as atrial flutter in a child.

This case highlights the importance of considering drug ingestion when the clinical features at presentation are unusual. To our knowledge, this is the first report of atrial flutter secondary to tricyclic antidepressant (TCA) overdose in a child.

Does adenosine A(1) receptor stimulation causes QRS prolongation by blocking beta adrenergic receptors in amitriptyline poisoning?

AIMS: To investigate the role of beta receptor blockade via adenosine A(1) receptor stimulation on amitriptyline-induced QRS prolongation. METHODS: Isolated rat hearts were randomized into three groups (n=8 for each group). After pretreatment with 5% dextrose (control) or DPCPX (8-cyclopentyl-1,3-dipropylxanthine), or propranolol + DPCPX, amitriptyline infusion was given to all groups. Intact beta adrenergic receptor response was verified with a bolus dose of isoproteranol (3 x 10(-5)M). RESULTS: Amitriptyline (5.5 x 10(-5)M) infusion following pretreatment with 5% dextrose or 10(-4)M DPCPX prolonged QRS by 40-110% and 30-75%, respectively. After the beta receptor blockade with 10(-2)M propranolol bolus, amitriptyline infusion following pretreatment with DPCPX prolonged QRS by 40-130%. Amitriptyline infusion following pretreatment with DPCPX (10(-4)M) shortened the QRS at 40, 50 and 60 min significantly when compared to propranolol+DPCPX group (168.8+/-4.9%, p<0.05; 170.8+/-6.9%, p<0.01; 174.0+/-6.9%, p<0.01, respectively). Amitriptyline infusion following pretreatment with 5% dextrose prolonged QRS duration significantly at 50th minutes (209.5+/-6.1%, p<0.05) compared to DPCPX pretreatment group. CONCLUSION: DPCPX pretreatment shortened amitriptyline-induced QRS prolongation. Beta adrenergic receptor blockade enhanced QRS prolongation shortened by DPCPX pretreatment. Adenosine A(1) receptor stimulation related to beta adrenergic receptor blockade may play a role in amitriptyline-induced QRS prolongation in isolated rat hearts.

Alleged breaches of "standards of medical care" in a patient overdose death possibly related to chronic opioid analgesic therapy, application of the controlled substances model guidelines: case report.

OBJECTIVES: The objectives of this medicolegal case report are the following: 1) to present details of a chronic pain patient (CPP) who was placed on chronic opioid analgesic therapy (COAT), and subsequently overdosed on multiple drugs, some of which were not prescribed by his COAT physician; 2) to present both the plaintiff's and defendant's (the COAT prescriber) expert witnesses' opinions as to the allegation that COAT prescribing was the cause of death; and 3) based on these opinions, to develop some recommendations on how pain physicians can utilize the use of Controlled Substances Model Guidelines in order to protect the patient and themselves from such an occurrence. METHODS: This is a case report of a CPP treated by a pain physician. RESULTS: Differences between the plaintiff's and defendant's expert's opinions are explained utilizing the Controlled Substances Model Guidelines. CONCLUSIONS: Some CPPs may withhold information critical to their COAT treatment. Application of the Controlled Substances Model Guidelines and the newer Federation of State Medical Boards' policy on opioid prescribing can be helpful in improving patient care and may be helpful in protecting the physician medicolegally.

Endoscopic removal of slow release clomipramine bezoars in two cases of acute poisoning.

INTRODUCTION: Acute gastroscopy is seldom advocated in cases of drug overdose. However, this intervention is sometimes recommended in cases where a pharmacobezoar of toxic tablets has formed. CASE REPORTS: We describe two patients who were admitted after major ingestion of slow release clomipramine. In one case an abdominal x-ray was highly suspicious of a large pharmacobezoar in the stomach and in the other case a tablet conglomerate totally obstructed the oesophagus. Both conditions were successfully managed by acute gastroscopy. DISCUSSION: There are limited and inconclusive recommendations in the literature concerning the optimal treatment of pharmacobezoars. CONCLUSION: This article provides further evidence that slow release clomipramine may be capable of forming a radio-opaque pharmacobezoar. The clinical courses in these two cases suggest that tablet removal by gastroscopy should be considered in selected cases of drug poisoning. Suspicion of a pharmacobezoar may warrant diagnostic investigations such as imaging studies and endoscopy.

Evaluation of relationship between arterial and venous blood gas values in the patients with tricyclic antidepressant poisoning.

INTRODUCTION: Determination of arterial blood gas (ABG) values is essential in the evaluation of patients with TCA poisoning. The relationship between arterial and venous blood gas pH has not been established in TCA poisoning. In TCA poisoning, blood vessels vasodilatation due to antidepressant-induced alpha-blockade and also metabolic acidosis may lead to arterialization of venous blood, which in turn enhances the relationship between ABG and VBG parameters. Therefore this study was designed to evaluate the relationship between ABG and VBG pH values in TCA poisoned patients. METHODS: This prospective study was performed in the Poisoning Emergency Department of Noor Hospital, Isfahan, Iran. Samples for arterial and venous blood gas analysis were obtained during initial evaluation of TCA-poisoned patients and 30 min after treatment with sodium bicarbonate. The venous blood gas samples were collected with samples for other blood tests at the time of intravenous line insertion. Laboratory data were recorded on a database form initiated in the emergency department and analyzed by paired student t-test. The degree of agreement between the arterial and venous pH measurements was evaluated by Bland and Altman method. RESULTS: Data from 50 TCA-poisoned patients were analyzed. There were significant differences between mean differences of ABG and VBG parameter values on the initial evaluation. There was also a relationship between arterial and venous pH on the initial evaluation. CONCLUSION: In TCA poisoning, the peripheral venous pH measurement is a valid and reliable substitute for arterial pH.

Coma blisters, peripheral neuropathy, and amitriptyline overdose: a brief report.

BACKGROUND: Coma blisters are most commonly associated with barbiturate and benzodiazepine overdose; however, they have also been described in association with many other substances, including amitriptyline. OBJECTIVE: To review the literature on the clinical manifestations of coma blisters in the setting of amitriptyline overdose. METHODS: Case report and literature review. RESULTS: Coma blisters in association with amitriptyline overdose have rarely been documented in the literature. Of the few reported cases, peripheral neuropathy has been present two (including our case report) out of four times. CONCLUSION: Amitriptyline is known to impair endothelial cell tight junction integrity. Thus, individuals with amitriptyline overdose may be predisposed to microvascular damage during the compression imposed from a comatose state. This may help to explain the tendency for patients to present with the interesting triad of coma, blisters, and neuropathy.

Radiopacity of clomipramine conglomerations and unsuccessful endoscopy: report of 4 cases.

BACKGROUND: The radiopacity of ingested substances may serve as a clue to the presence of particular compounds, as this characteristic varies considerably among medications and household products. Tablet conglomerations are also variably radiopaque. We report 4 cases of clomipramine poisoning associated with formation of radiopaque masses, believed to be clomipramine, in the area of the stomach. CASE REPORTS: Four patients were admitted to the Toxicological Intensive Care Unit after ingestions of, respectively, 8.5 g (180 tablets of mixed strength), 7.5 g (100 tablets), 10.5 g (140 tablets), and 4.5 g (60 tablets) of clomipramine, along with other sedatives and antipsychotics. In each case, a rounded density was observed in the gastric area on plain chest radiograph. The hospital courses of each patient were marked by tachycardia, hypotension, QRS and QT prolongation, seizures, and decreased mental status. Three of 4 patients underwent unsuccessful endoscopy to remove tablet fragments and subsequently suffered gastrointestinal hemorrhage requiring transfusion. All patients were discharged recovered from the hospital. DISCUSSION: Clomipramine, a potent tricyclic antidepressant, has been previously reported to be nonradiopaque, and has not been reported to induce formation of concretions. These cases suggest that massive ingestions of clomipramine may form bezoars which are radiopaque and may be associated with serious toxicity. Careful consideration should be given prior to the use of gastric endoscopy for the retrieval of tablet fragments since significant hemorrhage, attributed to the procedure itself rather than to clomipramine toxicity, may ensue.

[Progressive cerebellar atrophy following acute antidepressant intoxication].

A 37-year-old woman presented with acute cerebellar atrophy after ingesting toxic doses of tricyclic antidepressants in an attempt of suicide. Two hours after ingestion, she was comatose and showed myoclonus of the limbs, and eventually developed status epileptics. The patient underwent general anesthesia with thiopental, she had hyperpyrexia with elevated muscle enzymes and leukocytosis. These clinical and laboratory features suggested that she had serotonin syndrome (SS). After recovery from coma and hyperpyrexia that had lasted for 7 days, she showed cerebellar ataxia, and progressive cerebellar atrophy of CT scan. As well as neuroleptic malignant syndrome, the SS may cause cerebellar degeneration, probably due to sustained hyperpyrexia.