Between 1993 and 2004, patients with antidepressant poisoning admitted to an emergency department (ED) were analysed retrospectively with regard to demographics, clinical findings and treatment attempts. Age, gender, suicide attempts, classification of antidepressants, Glasgow Coma Scale (GCS) score, ECG findings, need for endotracheal intubation, follow-up period and Antidepressant Overdose Risk Assessment (ADORA) criteria were analysed by SPSS software. A total of 356 antidepressant poisoning cases were evaluated. Tricyclic antidepressants (TCA), especially opipramol and amitriptyline, were the most common agents (58.4%). The most frequent ECG finding was sinus tachycardia (40.7%, n=145). Endotracheal intubation was required in 9.6% of cases. Patients with TCA ingestion had a longer observation time in the ED, abnormal ECG findings, abnormal physical examination findings and more ADORA criteria, than patients who ingested selective serotonin re-uptake inhibitors (SSRI) (P=0.008, P=0.008, P<0.001, P<0.001). It was found that the patients who ingested TCA (P=0.001), poisoned with amitriptyline (P=0.001), patients with GCS scores of 8 and less (P=0.001), patients with two or more ADORA criteria (P=0.001), with seizures (P=0.001), with abnormal ECG (P=0.012), and patients with a history of two or more suicide attempts were intubated more frequently. Suicide attempts, classification of the antidepressant, ECG findings, seizure, GCS score and number of detected ADORA criteria affect the need for intubation in patients with antidepressant poisoning.

Adenosine antagonists were found to be effective in improving hypotension, QRS prolongation and survival time in our rat model of amitriptyline toxicity. Additionally, amitriptyline-induced cardiotoxicity was abolished by pretreatment with adenosine receptor antagonists. These results suggest that adenosine receptors may have a role in the pathophysiology of amitriptyline-induced cardiovascular toxicity. Adenosine A1 and A2a receptor antagonists may be promising agents for reversing amitriptyline-induced cardiovascular toxicity.

Objectives:The aim of this study was to evaluate the short and long-term impact of pharmacovigilance (PV) training on the 5th year medical students’ knowledge about definitions and on the awareness of the regulatory aspects in PV.Materials and Methods:In academic year 2010/11, the students completed structured, questionnaire before and just after training. They also completed the same questionnaire 1-year after the training.Results:The students’ knowledge about PV significantly increased after training in the short term (P < 0.001). However, the improvement decreased significantly in the long-term (P < 0.001). Although long-term scores were higher than the baseline score, the difference was not statistically significant. Total scores were 17.5 ± 2.0, 20.8 ± 2.0 and 18.0 ± 2.5; before, at short and long-term after the training.Conclusion:PV training increased the students’ knowledge significantly. However, in the long-term, the impact of the training is limited. Repeated training of PV should be planned.

Pancytopenia is a rare but serious adverse effect of low-dose methotrexate (MTX) sodium therapy, and this case report describes a very early-onset of pancytopenia and cutaneous lesions after three days of ingestion. A 64-year-old man was presented to Emergency Department with weakness, fever, poor appetite, nausea, and vomiting after he had had accidentally ingested MTX tablets (2.5 mg) twice a day for the last three days. On initial examination, several painful lesions in his oral mucosa and a cutaneous ulceration on his right foot were also observed. He had severe pancytopenia, poor kidney functions, and abnormal coagulation parameters. The blood level of MTX was found to be within therapeutic range. He was treated with leucovorine, intravenous antibiotics, and appropriate blood transfusions; he was discharged from hospital without any sequela. Pancytopenia associated with low-dose (cumulative dose of 15 mg in 3 days) MTX therapy had not been reported previously. The Naranjo probability scale showed pancytopenia and skin ulcer associated with low-dose MTX therapy as probable adverse reactions. Risk factors for pancytopenia such as renal insufficiency, hypoalbuminemia, low folate levels, concomitant infections, concomitant use of drugs, and folate supplementation were not identified in our patient. Although pancytopenia associated with low-dose MTX therapy is not expected as early as 3 days after initiation of the therapy, physicians should also be aware of this life threatening adverse effect during the very first days of MTX therapy for rheumatoid arthritis patients.

Amatoxins are one of the most potent toxins that cause hepatic and renal failure. However, this is the first report demonstrating an elevation of cardiac enzymes in a patient with Amanita phalloides poisoning. A 56-year-old male was admitted to the emergency department (ED) 42 h after an unknown type of mushroom ingestion. Hepatic, renal function tests, amylase and cardiac enzymes (troponin I, creatine kinase (CK), CK-MB isoenzyme and myoglobin) were found elevated in his blood chemistry. The electrocardiogram disclosed sinus tachycardia. Aggressive treatment with fluids, activated charcoal, penicillin G and silibinin were started. The patient was sent to hemodialysis because of anuria. During follow-up, biochemical parameters and clinical findings improved. The patient was discharged from the hospital following the arrangement of hemodialysis schedule because of the chronic renal failure. False elevations of cardiac markers may confuse the clinicians in differantial diagnosis of myocardial infarction in ED. In our patient, amatoxins that have bound the actin filaments within myocardiocytes or renal cells and/or its effects as circulating anti-troponin antibodies might result in elevation of cardiac markers. Elevated cardiac enzyme levels without any acute coronary syndrome are probable in mushroom poisoning cases involving amatoxin ingestion. Human & Experimental Toxicology (2007) 26, 757— 761

The aim of this study was to investigate the effect of glucagon on cardiovascular parameters in anesthetized rat model of tricyclic antidepressant overdose. Toxicity was induced by infusion of amitriptyline 0.94 mg/kg/min until a 40–45% of reduction in mean arterial pressure was observed. Amitriptyline infusion rats were then randomized into three groups. Control group of rats (group 1) received a bolus of 5% dextrose followed by the continuous infusion of dextrose, whereas treatment groups received 1 mg/kg (group 2) or 2 mg/kg (group 3) bolus doses of glucagon followed by continuous infusion (0.1 mg/kg/min) of glucagons for 60 min. Mean arterial pressure, heart rate, and electrocardiogram were recorded. Amitriptyline caused a significant decrease in mean arterial pressure and a prolongation in QRS, yet it did not change the heart rate. High-bolus dose of glucagon (2 mg/kg) followed by glucagon infusion significantly increased mean arterial pressure at 40, 50, and 60 min ( P < 0.05) and shortened the prolonged QRS at 50 and 60 min ( P < 0.05) when compared with control group. There was also a significant increase in heart rate. In conclusion, bolus doses followed by a continuous infusion of glucagon were found to be effective in reversing the hypotension and QRS prolongation in the rat model of amitriptyline toxicity. Further studies are needed to reveal the exact mechanism of the proposed effect.

While 10(-4) M DPCPX shortened QRS prolongation, 10(-5) M CSC prolonged QRS duration in the isolated rat hearts with prolonged QRS duration induced by 5.5 x 10(-5)M amitriptyline. An adenosine A(1) receptor antagonist, DPCPX, might shorten amitriptyline-induced QRS prolongation by activating beta adrenergic receptors.

Because of the large number of unintentional caustic exposures, parent education is very important to decrease the caustic exposures in children.