Evaluation of voriconazole related adverse events in pediatric patients with hematological malignancies.

BACKGROUND: Despite therapeutic drug monitoring and pharmacogenetic-guided dose selection are recommended for pediatric patients, safety of voriconazole is mostly monitored by clinical assessment. Having comprehensive knowledge of safety profile and distinguishing incidental events from the reactions that are truly related to voriconazole use are crucial for safer and uninterrupted treatment. OBJECTIVES: This study aimed to address adverse reactions during the first month of voriconazole use by systematically evaluating retrospective records of all adverse events. Patients/Methods: It is a single-center, retrospective analysis of patients who received voriconazole from 1 September 2010 to 1 September 2020. Severity of abnormal findings in medical records were systematically graded. Causality between voriconazole and the events was evaluated by Liverpool Causality Assessment Tool (LCAT), Naranjo Algorithm and World Health Organization Causality Assessment System. The events with possible or probable causal relation to voriconazole are classified as adverse reaction. RESULTS: Records of 45 patients included in the study. The overall frequency of adverse reactions was 51.1%. Hepatobiliary laboratory adverse reactions identified in 48.9% of the patients and led to treatment discontinuation in 20.0%. Amylase and lipase elevation (2.2%), ventricular extra systoles (2.2%), hallucination and nightmares (2.2%) were other adverse reactions. CONCLUSIONS: Hepatobiliary abnormalities were the most common adverse reactions and the most common cause of treatment discontinuation. For safer treatment in critically ill patients, the dose should be personalized. To clearly identify the accurate frequency and the causality of all adverse reactions, prospective studies with much larger sample size are needed.

Urinary microbiota; Which non-invasive urine collection method should we use?

OBJECTIVE: The aim of this study is to establish the optimal non-invasive urine sample collection method for the microbiota studies. METHODOLOGY: Twelve men with bladder carcinoma underwent first voided and midstream urine collection. Urine samples were analysed using V3-V4 regions of bacterial 16s ribosomal RNAs. Bacterial groups with relative abundance above 1% were analysed in first voided urine and midstream urine samples at phylum, class, order and family level. At the genus level, all of the identified bacterial groups' relative abundances were analysed. The statistical significance (P < .05) of differences between first voided and midstream urine sample microbiota was evaluated using the Wilcoxon test. RESULTS: According to the analysis, 8 phyla, 14 class, 23 orders, 39 families and 29 different genera were identified in the first voided and the midstream urine samples. Statistical differences were not identified between first voided and midstream urine samples of all bacteria groups except the Clostridiales at order level (p:0.04) and Clostridia at class level (P: .04). CONCLUSIONS: Either first voided or midstream urine samples can be used in urinary microbiota studies as we determined that there is no statistically significant difference between them regarding the results of 16s ribosomal RNA analysis.

Methotrexate for recurrent chronic rhinosinusitis with nasal polyps: A randomized, controlled, phase 2 clinical trial.

OBJECTIVE: This randomized, controlled, open-label, phase 2 clinical trial aimed to assess the efficacy and safety of low-dose methotrexate as maintenance therapy for recurrent postoperative chronic rhinosinusitis with nasal polyps (CRSwNPs). METHODS: Forty-one patients with CRSwNPs who experienced postoperative polyp recurrence(s) were randomly divided into three groups to receive one of the following treatments for 8 weeks: daily intranasal mometasone furoate monohydrate 200 mcg (control [intranasal corticosteroids (INCS)] arm, n = 13]); daily per oral methylprednisolone 8 mg (oral corticosteroids [OCS] arm, n = 14); and once weekly per oral 10 mg methotrexate (MTX arm, n = 14). All patients were assessed at three clinical visits according to the Lund-Kennedy endoscopic grading system (LKES), visual analog scale (VAS), Turkish version of the Sinonasal Outcome Test-22 (SNOT-22), peak nasal inspiratory flow (PNIF), butanol olfactory threshold test (BuOT), serum total IgE level, presence of peripheral eosinophilia, serum biochemical assays, and adverse events. RESULTS: All efficacy outcome measures significantly improved in all three groups, except for the nonrecovery of peripheral eosinophilia in the INCS group. There was no significant difference among the groups in terms of LKES scores. Scores for the Turkish version of the SNOT-22, PNIF, BuOT, and serum IgE levels were also similar among the groups. However, total VAS scores recovered significantly better in the INCS group than in the MTX group. Serum biochemical assays remained normal in all groups. Adverse events were minor and observed only in the OCS group. CONCLUSION: Low-dose MTX was a safe and effective maintenance therapy for patients with recurrent postoperative CRSwNPs.

Effect of the selective mitochondrial KATP channel opener nicorandil on the QT prolongation and myocardial damage induced by amitriptyline in rats.

OBJECTIVES: The aim of this study is to evaluate the protective effect of nicorandil, a selective mitochondrial KATP channel opener, on QT prolongation and myocardial damage induced by amitriptyline. METHODS: The dose of amitriptyline (intraperitoneal, i.p.) that prolong the QT interval was found 75 mg/kg. Rats were randomized into five groups the control group, amitriptyline group, nicorandil (selective mitochondrial KATP channel opener, 3 mg/kg i.p.) + amitriptyline group, 5-hdyroxydecanoate (5-HD, selective mitochondrial KATP channel blocker, 10 mg/kg i.p.) + amitriptyline group and 5-HD + nicorandil + amitriptyline group. Cardiac parameters, biochemical and histomorphological/immunohistochemical examinations were evaluated. p < 0.05 was accepted as statistically significant. KEY FINDINGS: Amitriptyline caused statistically significant prolongation of QRS duration, QT interval and QTc interval (p < 0.05). It also caused changes in tissue oxidant (increase in malondialdehyde)/anti-oxidant (decrease in glutathione peroxidase) parameters (p < 0.05), myocardial damage and apoptosis (p < 0.01 and p < 0.001). While nicorandil administration prevented amitriptyline-induced QRS, QT, QTc prolongation (p < 0.05), myocardial damage and apoptosis (p < 0.05), it did not affect the changes in oxidative parameters (p > 0.05). CONCLUSIONS: Our results suggest that nicorandil, a selective mitochondrial KATP channel opener, plays a protective role in amitriptyline-induced QT prolongation and myocardial damage. Mitochondrial KATP channel opening and anti-apoptotic effects may play a role in the cardioprotective effect of nicorandil.

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.

An alternative antidote therapy in amitriptyline-induced rat toxicity model: theophylline.

We planned this study in order to investigate the effects of theophylline on cardiovascular parameters in an anaesthetized rat model of amitriptyline toxicity. In the preliminary study, we tested theophylline as 1 mg/kg of bolus, followed by a 0.5-mg/kg infusion. Toxicity was induced by the infusion of 0.94 mg/kg/min of amitriptyline up to the point of a 40-45% inhibition of mean arterial pressure (MAP). The rats were randomized to two groups: a group of 5% dextrose bolus followed by 5% dextrose infusion, and another group with theophylline bolus followed by infusion. Amitriptyline caused a significant decrease in MAP and prolongation in QRS; however, it did not alter heart rate (HR). When compared to the dextrose group, theophylline administration increased MAP, shortened prolonged QRS duration, and increased HR (P < 0.05, respectively). There was no statistically significant difference in the results of arterial blood-gas analyses among the groups (P > 0.05). Bolus doses followed by a continuous infusion of theophylline were found to be effective in reversing the hypotension and QRS prolongation seen in amitriptyline toxicity. One of the possible explanations of this beneficial effect is nonselective adenosine antagonism of theophylline. Further studies are needed to reveal the exact mechanism of the observed effect.

Necrotic arachnidism of the eyelid due to Loxosceles rufescens spider bite.

A 69-year-old woman was awakened with redness and swelling of the left upper eyelid a few days before her presentation. She also noticed a dead spider on her bed. Ophthalmic examination revealed severe left periorbital hyperemia, edema and a wide necrotic area on the upper eyelid. Systemic condition of the patient was well. She was hospitalized with the diagnosis of necrotic arachnidism of the left upper eyelid. Systemic corticosteroid and antibiotic treatment was commenced. No surgical intervention was carried out. A week later, whole upper eyelid was covered with a black eschar. This black eschar shrank with time, and it detached completely within 8 weeks and the lesion healed without a disfiguring scar. Meanwhile, the offending spider was identified as Loxosceles rufescens. Although rare, eyelid may be a biting site for Loxosceles spiders and a favorable result may be obtained with conservative management.

Therapeutic effects of melatonin on an ovalbumin-induced allergic rhinitis model in rats.

OBJECTIVE: We aimed to investigate the therapeutic effects of melatonin in an experimental AR model. METHODS: Thirty-two Wistar rats were randomised into four groups (n = 8 each). The experimental AR model was established in the saline (SF), ethanol, and melatonin groups via intraperitoneal (i.p.) injections and intranasal application of ovalbumin. The SF, ethanol, and melatonin groups received daily i.p. saline, 2% ethanol dissolved in saline, and 10 mg/kg melatonin dissolved in 2% ethanol and saline. The control group received the same amount of i.p. and intranasal saline. Total nasal symptom scores were recorded in all rats on days 1 (baseline), 15, 20, 25, and 30. Serum ovalbumin-specific IgE, IL-13, and melatonin levels were measured on days 1 (baseline), 15, and 30. The nasal mucosa of all rats was scored histopathologically. RESULTS: The total nasal symptom scores and serum ovalbumin-specific IgE values of the SF, ethanol, and melatonin groups were significantly higher on day 15 than those of the control group. On day 30, the scores and serum ovalbumin-specific IgE values of the melatonin group were similar to those of the control, whereas the SF and ethanol groups had statistically higher scores. The histological scores of the SF and ethanol groups were significantly higher than those of the control and melatonin groups, but no significant difference was found between the melatonin and control groups. CONCLUSION: Melatonin reduced total nasal symptom scores and serum ovalbumin-specific IgE levels and improved histological inflammation parameters in the ovalbumin-induced rat experimental AR model.

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.

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.

Protective effect of an adenosine A1 receptor agonist against metamidophos-induced toxicity and brain oxidative stress.

The aim of this study was to evaluate the effects of different doses of an adenosine A(1) selective agonist, phenylisopropyl adenosine (PIA), on metamidophos-induced cholinergic symptoms, mortality, diaphragm muscle necrosis, and brain oxidative stress. A LD(50) dose of metamidophos (20 mg/kg body weight, p.o.) was followed by 1 mL/kg body weight of 0.9% NaCl or 1 mg/kg, 2 mg/kg, 3 mg/kg, or 5 mg/kg body weight PIA ip. Incidence of clinical signs including chewing, salivation, convulsion, and respiratory distress did not show any significant difference among all treatment groups (p > 0.05). PIA was found to be effective to reverse the necrotic changes in diaphragm muscle induced by metamidophos significantly in all groups. Brain Thiobarbituric Acid Reactive Substance (TBARS) levels were significantly increased after the metamidophos poisoning. Administration of 2 to 5 mg/kg body weight PIA decreased brain TBARS levels compared to 0.9% NaCl treated rats. The results indicate that, although different doses of PIA reduced the OP-induced oxidative stress and diaphragm necrosis, a single dose of PIA was not able to recover cholinergic signs and symptoms of metamidophos poisoning.

Antivenom use in bite and sting cases presenting to a public hospital.

BACKGROUND: To evaluate the distribution of bite and sting cases presenting to a district public hospital and the use of antivenom in scorpion sting and snake bite cases. METHODS: The demographic characteristics of patients with bites/stings reporting to a public hospital in 2014, the agent involved, the season of reporting, severity of clinical findings during presentation, and use of antivenom in scorpion sting and snake bite cases were evaluated retrospectively. χ2 test was used for statistical analysis. RESULTS: Bite and sting cases comprised 0.5% of all the patients reporting to the hospital's emergency department, with scorpion sting cases comprising almost half (54.2%) of these hospital presentations, followed by Hymenoptera (bee and wasp) sting (30.8%) and snake bite (5.5%) cases. Unnecessary antihistamine administration was found to be significantly high in asymptomatic patients (p=0.00006). Furthermore, antivenom use was found to be significantly high in patients with scorpion sting and snake bite despite the absence of systemic or local indications (p<0.0001, χ2=80.595). CONCLUSION: The study results showed that antivenom was used in scorpion sting and snake bite cases even when it was not indicated. Therefore, primary practitioners should be provided training for management of envenomation cases and should be made aware of the updated guidelines and references to raise their knowledge levels.

A Comparison of the Effectiveness of Silibinin and Resveratrol in Preventing Alpha-Amanitin-Induced Hepatotoxicity.

Amanita phalloides species mushrooms containing alpha-amanitin (α-AMA) are responsible for the majority of fatal mushroom intoxications and can lead to severe poisonings resulting in hepatotoxicity and acute hepatic failure. Existing antidotes, such as silibinin, are not sufficiently effective in the prevention and/or resolution of α-AMA-induced hepatotoxicity. We investigated the effects of resveratrol on α-AMA-induced hepatotoxicity and compared with silibinin, a known antidote using in vivo and in vitro toxicity models. In the in vivo protocol, resveratrol (30 mg/kg) was given simultaneously with α-AMA (α-AMA + SR) or 12 (α-AMA + 12R) or 24 (α-AMA + 24R) hr after α-AMA administration. Silibinin (5 mg/kg) (α-AMA + Sil) and normal saline (α-AMA + NS) were given simultaneously with α-AMA. We found that liver transaminase levels in α-AMA + SR and α-AMA + 12R groups and histomorphologic injury score in the α-AMA + SR, α-AMA + 12R, α-AMA + 24R and α-AMA + Sil groups were significantly lower than that of the α-AMA + NS group. Resveratrol decreased mononuclear cell infiltration, necrosis and active caspase-3 immunopositivity in the liver. In the in vitro protocol, the effects of resveratrol and silibinin were evaluated in a reduction in cell viability induced by α-AMA in THLE-2 and THLE-3 hepatocytes. Neither resveratrol nor silibinin was found to be effective in increasing cell viability decreased by α-AMA + NS. As a conclusion, resveratrol was found to be effective in α-AMA-induced hepatotoxicity with its anti-inflammatory properties in in vivo conditions. It is a promising compound with the potential for use in the treatment of hepatotoxicity associated with Amanita phalloides type mushroom poisonings.

Effects of adenosine receptor antagonists on amitriptyline-induced vasodilation in rat isolated aorta.

BACKGROUND: Although we have previously demonstrated the beneficial effects of adenosine receptor antagonists in preventing cardiovascular toxicity of amitriptyline in rats, it is not clear whether adenosine receptors in heart or in vasculature are dominant. The aim of the current study was to investigate the role of adenosine A(2a) receptors on amitriptyline-induced vasodilation in rat isolated aorta. METHODS: After determining EC(80) of noradrenalin (NA) (the concentration of noradrenalin that produces 80% of maximal contractile response) as 10(-5)M, the IC(50) value of amitriptyline was measured in rat isolated aorta (the drug concentration causing a half- maximal inhibition of contractile responses to NA); IC(50) of amitriptyline was then compared in the presence of the DPCPX (a selective adenosine A(1) antagonist), CSC (a selective A(2a) antagonist) or DMSO (a solvent for adenosine antagonists). Statistical analysis was done using the Student t test. RESULTS: Amitriptyline-inhibited 49.9 +/- 3.7 % contractile response to NA on aorta segments at 1.8 x 10(-5)M (IC(50)). While DPCPX increased amitriptyline-induced inhibition on contractile response to NA dose dependently, CSC decreased the contractile response to NA only at 10(-5)M. DMSO did not change amitriptyline-induced IC(50). CONCLUSION: Adenosine A(2a) receptor stimulation seems to be responsible partly for amitriptyline-induced vasodilation and hypotension since the adenosine A(1) antagonist, DPCPX, increased amitriptyline-induced vasodilation in rat isolated aorta.

A retrospective evaluation of analgesic exposures from Izmir, Turkey.

The objective of this study is to analyze exposures concerning analgesics that were reported to Dokuz Eylul University Drug and Poison Information Center (DPIC) and admitted to the Department of Emergency Medicine in Dokuz Eylul University Hospital (EMDEU) between 1993 and 2004. Demographics of the patients, characteristics of analgesic exposures, performed treatment attempts and outcome of the poisoned patients were recorded on standard data forms and were then entered into a computerized database program. Statistical analysis was performed by using the chi-square test. The DPIC recorded 55 962 poisoning calls, 48 654 (86.9%) of them related to medicines. Analgesics accounted for 16.3% (7 939 cases) of all medicine-related exposures; among them 446 exposures were admitted to EMDEU. More than half of the analgesic exposure calls and admitted cases involved adults (55.9%, 4 440). Females dominated in all age groups (70.3%, 5 578). Mean age was 20.2 +/- 11.8. The most involved analgesics were paracetamol (47.9%), propionic acid derivatives (16.1%) and salicylates (13.7%). Most of the poisonings were intentional (75.1%), especially in 19-29 years age group of adults and 13-18 years age group of children. Most of the patients reported to DPIC and admitted to EMDEU were asymptomatic (84.4% and 54.7%, respectively). Gastrointestinal decontamination methods were performed more frequently for admitted poisoning cases before hospital admission than reported poisoning cases (61% vs. 23%). Paracetamol ingestion was the most common cause of analgesic exposures reported to our DPIC. Most of the analgesic exposures reported to DPIC were asymptomatic or mild. DPICs have an important role for the referral of analgesic exposures without unnecessary gastrointestinal decontamination procedures.

Renal and hepatic injury with elevated cardiac enzymes in Amanita phalloides poisoning: a case report.

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 differential 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.

The role of adenosine triphosphate-regulated potassium channels in propofol-induced beneficial effect on contractile function of hypercholesterolemic isolated rabbit hearts.

OBJECTIVE: To investigate the role of adenosine triphosphate-regulated potassium (KATP) channels in the propofol-induced changes in the contractile function of hypercholesterolemic rabbit hearts. METHODS: This study was carried out in the Department of Pharmacology Laboratory, Faculty of Medicine, Dokuz Eylul University, Izmir, Turkey during the period January to December 2003. Twenty-two isolated rabbit hearts were grouped into 4. Group I (n=6) were infused with 50 microM propofol during a 60 minutes perfusion. Group II (n=6) were also infused with 100 microM propofol over the same period. Group III (n=5) was perfused with solutions containing 10 microM glybenclamide and group IV (n=5) 100 microM diazoxide for 5 minutes before and during a 60 minutes infusion with 100 microM propofol. RESULTS: The 50 microM propofol infusion decreased left ventricular pressure (LVP) significantly (p<0.05) but it did not change dP/dt max and dP/dt min. The 100 microM propofol infusion caused a significant increase in LVP at 20 minutes. Furthermore, a 100 microM propofol infusion resulted in a significant increase in maximal positive left ventricular pressure (dP/dt max) and maximal negative left ventricular pressure (dP/dt min) compared to baseline (p<0.05). The increase in dP/dtmax and dP/dt min induced by 100 microM propofol was inhibited by glybenclamide (p<0.05), a KATP channel blocker, but was not affected by diazoxide (p>0.05), a KATP channel opener. CONCLUSION: The activation of KATP channels seems to be one of the mechanisms by which propofol induced beneficial effect on contractility of myocardium in hypercholesterolemic rabbit hearts.

Emergency department visits caused by adverse drug reactions: results of aTurkish university hospital.

BACKGROUND/AIM: We aimed to evaluate adverse drug reaction (ADR)-related emergency department (ED) visits in the ED of the Dokuz Eylül University Hospital prospectively. MATERIALS AND METHODS: Patients who were admitted to the ED during 1-week periods of four different seasons between July 2010 and April 2011 were enrolled. Demographics of patients, previous ADR history, clinical progress, and outcomes were recorded. Causality assessment was done according to World Health Organization Uppsala Monitoring Centre categories. ADRs were categorized as certain, probable, or possible. RESULTS: Patients who were on medications (26.5%, n = 1838) were evaluated for ADR-related ED admissions. ADRs accounted for 5.9% of cases (n = 108). The most frequently affected systems were the gastrointestinal (35.2%, n = 38), dermatological (23.1%, n = 25), and hematological (10.2%, n = 11) systems (7.4%, n = 8). The most common causes of ADRs were antiinfectives (31.6%, n = 33). Amoxicillin, Coumadin, and paracetamol were the most common medications that caused ADRs. CONCLUSION: Nearly 6% of the admissions were ADR-related. ADRs should always be considered when patients who are on medication are admitted to the ED. Multicenter epidemiologic studies are required to know the real rates of ADR cases in EDs in Turkey.

The Effects of the Adenosine Receptor Antagonists on the Reverse of Cardiovascular Toxic Effects Induced by Citalopram In-Vivo Rat Model of Poisoning.

BACKGROUND: Citalopram is a selective serotonin reuptake inhibitor that requires routine cardiac monitoring to prevent a toxic dose. Prolongation of the QT interval has been observed in acute citalopram poisoning. Our previous experimental study showed that citalopram may be lead to QT prolongation by stimulating adenosine A1 receptors without affecting the release of adenosine. AIMS: We examined the effects of adenosine receptor antagonists in reversing the cardiovascular toxic effects induced by citalopram in rats. STUDY DESIGN: Animal experimentation. METHODS: Rats were divided into three groups randomly (n=7 for each group). Sodium cromoglycate (20 mg/kg) was administered to all rats to inhibit adenosine A3 receptor mast cell activation. Citalopram toxicity was achieved by citalopram infusion (4 mg/kg/min) for 20 minutes. After citalopram infusion, in the control group (Group 1), rats were given an infusion of dextrose solution for 60 minutes. In treatment groups, the selective adenosine A1 antagonist DPCPX (Group 2, 8-cyclopentyl-1,3-dipropylxanthine, 20 µg/kg/min) or the selective A2a antagonist CSC (Group 3, 8-(3-chlorostyryl)caffeine, 24 µg/kg/min) was infused for 60 minutes. Mean arterial pressure (MAP), heart rate (HR), QRS duration and QT interval measurements were followed during the experiment period. Statistical analysis was performed by ANOVA followed by Tukey's multiple comparison tests. RESULTS: Citalopram infusion reduced MAP and HR and prolonged the QT interval. It did not cause any significant difference in QRS duration in any group. When compared to the control group, DPCPX after citalopram infusion shortened the prolongation of the QT interval after 40, 50 and 60 minutes (p<0.01). DPCPX infusion shortened the prolongation of the QT interval at 60 minutes compared with the CSC group (p<0.05). CSC infusion shortened the prolongation of the QT at 60 minutes compared with the control group (p<0.05). CONCLUSION: DPCPX improved QT interval prolongation in citalopram toxicity. The results of this study show that mechanism of cardiovascular toxicity induced by citalopram may be related adenosine A1 receptor stimulation. Adenosine A1 receptor antagonists may be used for the treatment of citalopram toxicity.

Short and long-term impact of pharmacovigilance training on the pharmacovigilance knowledge of medical students.

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.