RESUMEN
Alpha-amanitin (α-AMA), the primary toxin of Amanita phalloides, is known to cause nephrotoxicity and hepatotoxicity. Resveratrol is an antioxidant that has shown efficacy in many nephrotoxicity models. The aim of this study was to investigate the effects of resveratrol against the early and late stages of α-AMA-induced nephrotoxicity, compared to those of silibinin, a well-known antidote for poisoning by α-AMA-containing mushrooms. Mice kidney tissues were obtained from five groups: (1) α-AMA + NS (simultaneous administration of α-AMA and normal saline), (2) α-AMA + SR (simultaneous administration of α-AMA and resveratrol), (3) α-AMA + 12R (resveratrol administration 12 h after α-AMA administration), (4) α-AMA + 24R (resveratrol administration 24 h after α-AMA administration), and (5) α-AMA + Sil (simultaneous administration of α-AMA and silibinin). Histomorphological and biochemical analyses were performed to evaluate kidney damage and oxidant-antioxidant status in the kidney. Scores of renal histomorphological damage decreased significantly in the early resveratrol treatment groups (α-AMA + SR and α-AMA + 12R), compared to those in the α-AMA + NS group (p < 0.05). Catalase levels increased significantly in the α-AMA + SR group, compared to those in the α-AMA + NS group (p < 0.001). Early resveratrol administration within 12 h after α-AMA ingestion may reverse the effects of α-AMA-induced nephrotoxicity, partly through its antioxidant action, thereby suggesting its potential as a treatment for poisoning by α-AMA-containing mushrooms.
Asunto(s)
Alfa-Amanitina/toxicidad , Enfermedades Renales/inducido químicamente , Enfermedades Renales/tratamiento farmacológico , Resveratrol/uso terapéutico , Animales , Antioxidantes/metabolismo , Antioxidantes/uso terapéutico , Glutatión Peroxidasa , Riñón/metabolismo , Malondialdehído , Ratones , Ratones Endogámicos BALB C , Oxidantes/metabolismo , Superóxido DismutasaRESUMEN
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.
Asunto(s)
Antirreumáticos/efectos adversos , Metotrexato/efectos adversos , Pancitopenia/inducido químicamente , Úlcera Cutánea/inducido químicamente , Antibacterianos/uso terapéutico , Transfusión Sanguínea , Relación Dosis-Respuesta a Droga , Humanos , Inyecciones Intravenosas , Leucovorina/uso terapéutico , Masculino , Persona de Mediana Edad , Pancitopenia/patología , Pancitopenia/terapia , Úlcera Cutánea/patología , Úlcera Cutánea/terapia , Complejo Vitamínico B/uso terapéuticoRESUMEN
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.
Asunto(s)
Amitriptilina/toxicidad , Antidepresivos Tricíclicos/toxicidad , Presión Sanguínea/efectos de los fármacos , Enfermedades Cardiovasculares/tratamiento farmacológico , Sistema Cardiovascular/efectos de los fármacos , Fármacos Gastrointestinales/uso terapéutico , Glucagón/uso terapéutico , Frecuencia Cardíaca/efectos de los fármacos , Animales , Presión Sanguínea/fisiología , Enfermedades Cardiovasculares/inducido químicamente , Sistema Cardiovascular/fisiopatología , Modelos Animales de Enfermedad , Electrocardiografía , Fármacos Gastrointestinales/administración & dosificación , Glucagón/administración & dosificación , Sistema de Conducción Cardíaco/efectos de los fármacos , Sistema de Conducción Cardíaco/fisiopatología , Frecuencia Cardíaca/fisiología , Infusiones Intravenosas , Inyecciones Intravenosas , Masculino , Ratas , Ratas WistarRESUMEN
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.
Asunto(s)
Antidepresivos/envenenamiento , Adolescente , Adulto , Anciano , Antidepresivos Tricíclicos/envenenamiento , Electrocardiografía/efectos de los fármacos , Servicio de Urgencia en Hospital , Femenino , Escala de Coma de Glasgow , Hospitalización , Humanos , Unidades de Cuidados Intensivos , Intubación Intratraqueal , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Medición de RiesgoRESUMEN
The objective of this study was to evaluate the effects of an adenosine A1 agonist, phenylisopropyl adenosine (PIA), on metamidophos poisoning compared to specific antidotes. Rats were poisoned with metamidophos (30 mg/kg, oral) and observed for 24 hours. One group received sodium chloride (1 mL/kg) and four experimental groups received atropine (5 mg/kg), pralidoxime (PAM, 20 mg/kg), atropine/PAM (5/20 mg/kg) or PIA (1 mg/kg) intraperitoneally. Atropine reduced salivation and prevented respiratory distress when compared to sodium chloride-treated rats. Treatment with PAM did not cause any suppression of cholinergic signs. Atropine and PAM combination prevented salivation, convulsion and respiratory distress. PIA delayed initial time of the salivation, convulsion and time to death. However, PIA was found ineffective against the metamidophos-induced cholinergic symptoms and mortality. All treatments, except PIA, lead to survival of these animals. Acetylcholinesterase (AChE) activity was not normalized by PIA or PAM. PIA prevented metamidophos-induced diaphragmatic muscle necrosis as much as PAM. In conclusion, a single dose of PIA was unable to protect the rats from metamidophos toxicity. Further studies are needed involving a combination of PAM and/or atropine with repeated doses of PIA to clarify the efficacy of adenosine agonists in OP poisoning.
Asunto(s)
Agonistas del Receptor de Adenosina A1 , Antídotos/farmacología , Insecticidas/envenenamiento , Compuestos Organotiofosforados/envenenamiento , Fenilisopropiladenosina/farmacología , Animales , Antídotos/administración & dosificación , Atropina/administración & dosificación , Reactivadores de la Colinesterasa/administración & dosificación , Colinesterasas/sangre , Colinesterasas/metabolismo , Diafragma/efectos de los fármacos , Diafragma/patología , Interacciones Farmacológicas , Masculino , Modelos Animales , Antagonistas Muscarínicos/administración & dosificación , Fenilisopropiladenosina/administración & dosificación , Intoxicación/sangre , Intoxicación/mortalidad , Compuestos de Pralidoxima/administración & dosificación , Ratas , Ratas Wistar , Respiración/efectos de los fármacos , Salivación/efectos de los fármacos , Tasa de Supervivencia , Factores de TiempoRESUMEN
A case report of dramatic increases in serum digoxin levels after alprazolam administration prompted our investigation. Twelve inpatients receiving long-term digoxin (0.25 mg daily) randomly received oral administration of either 1.0 or 0.5 mg alprazolam per day for 7 days. In each dosage group, three patients were older than and three were younger than 65 years of age. The area under the concentration-time curve for serum digoxin increased significantly in patients receiving 1 mg alprazolam daily, and this increase was more pronounced in patients older than 65 years of age. Clinical digoxin toxicity developed in one elderly patient who was receiving 1 mg/day alprazolam.
Asunto(s)
Envejecimiento/metabolismo , Alprazolam/farmacología , Digoxina/farmacocinética , Anciano , Digoxina/sangre , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Humanos , Persona de Mediana EdadRESUMEN
OBJECTIVE: To investigate the excretion of gentamicin into human breast milk and resulting serum gentamicin levels in nursing newborn infants. METHODS: Women delivered by cesarean received gentamicin, 240 mg/day (80 mg intramuscularly three times a day) for 5 days postpartum. On day 4, maternal serum samples were collected 1 and 7 hours after gentamicin administration. Milk samples were collected 1, 3, 5, and 7 hours following administration. The infants were fed 1 hour after gentamicin administration, and serum samples were collected from the newborns 1 hour later. The concentrations of gentamicin were measured by a fluorescence polarization immunoassay. RESULTS: The mean (+/- standard deviation) maternal serum gentamicin levels at 1 and 7 hours were 3.94 +/- 1.12 and 1.02 +/- 0.78 microgram/mL, respectively. Milk gentamicin levels were: 0.42 +/- 0.26, 0.48 +/- 0.17, 0.49 +/- 0.17, and 0.41 +/- 0.25 microgram/mL at 1, 3, 5, and 7 hours, respectively. The mean milk:plasma gentamicin ratios were 0.11 and 0.44 at 1 and 7 hours, respectively. The correlation between maternal peak serum levels and milk levels was not statistically significant (P > .05). Detectable (above 0.27 microgram/mL) gentamicin levels were found in five of the ten newborn serum samples, with a mean level of 0.41 +/- 0.05 microgram/mL. CONCLUSION: Gentamicin is transferred into breast milk, and half of nursing newborn infants have detectable serum gentamicin levels.
Asunto(s)
Lactancia Materna , Gentamicinas/metabolismo , Recién Nacido/sangre , Leche Humana/metabolismo , Adulto , Femenino , Gentamicinas/administración & dosificación , Gentamicinas/farmacocinética , Humanos , Periodo PospartoRESUMEN
Amikacin is usually administered to the patients during open heart surgery immediately after cardiopulmonary bypass (CPB) because the serum levels of this drug may decrease due to the volume overload and hemodilution caused by intravenously administered fluids (1.2-2 liters prime solution). We investigated whether this application of amikacin is necessary immediately after CPB. A total of ten patients from Dokuz Eylül University Hospital, Department of Thoracic and Cardiovascular Surgery, who were scheduled for open heart surgery were studied. Serum sodium, potassium, blood urea nitrogen and creatinine values of the patients were found to be within normal limits before the operation. Amikacin was administered to patients just before open heart surgery and 2 ml blood samples were collected from all patients 15 minutes after the drug administration, just before cardiopulmonary by-pass (CPB), at the 30th and 60th minutes of the CPB, after CPB and after the cessation of operation, 4 hours after drug administration. A significant decrease was observed between the values of 10 patients by ANOVA (p < 0.05). Serum amikacin values were found to be 9.80 +/- 0.96 micrograms/ml at the end of the operation, 4 hours after the drug administration. Since serum amikacin levels do not fall below the trough concentrations at the end of the fourth hour we conclude that it is unnecessary to repeat the dose at the end of the operation.
Asunto(s)
Amicacina/administración & dosificación , Antibacterianos/administración & dosificación , Procedimientos Quirúrgicos Cardíacos/métodos , Adulto , Anciano , Amicacina/sangre , Antibacterianos/sangre , Puente Cardiopulmonar , Esquema de Medicación , Femenino , Humanos , Cuidados Intraoperatorios , Masculino , Persona de Mediana EdadRESUMEN
Theophylline and benzodiazepines are frequently combined in clinical practice. Because of a number of case reports about antagonism of benzodiazepine-induced sedation by theophylline, we investigated serum alprazolam levels in a convenient sample of pulmonary medicine inpatients receiving theophylline and no theophylline. One mg of alprazolam was given daily for seven days to 6 patients receiving theophylline and 7 patients not receiving theophylline treatment. On days 2 through 7, trough serum alprazolam levels were measured. On day 7, blood samples were collected before (0 hour), and at 3, 6, 9 and 12 hours after alprazolam administration. In patients receiving theophylline, serum trough alprazolam levels were significantly lower during each day of the study. In patients receiving no theophylline, serum alprazolam levels were in the therapeutic range, except for two patients who had high alprazolam levels. In this small study, serum alprazolam levels were found to be consistently below the therapeutic range in patients receiving chronic theophylline treatment. Previously reported antagonism of anxiolytic effects of benzodiazepines by theophylline is probably due to the lower serum benzodiazepine levels in these patients.
Asunto(s)
Alprazolam/sangre , Teofilina/farmacología , Adulto , Anciano , Enfermedad de la Arteria Coronaria/sangre , Interacciones Farmacológicas , Quimioterapia Combinada , Femenino , Insuficiencia Cardíaca/sangre , Humanos , Enfermedades Pulmonares/sangre , Masculino , Persona de Mediana Edad , Factores de TiempoRESUMEN
The effects of captopril on serum digoxin concentrations were studied in 8 patients with severe (NYHA Class IV) congestive heart failure. Serum digoxin concentrations were determined before and after the administration of captopril for 1 week in patients on chronic digoxin therapy. Each patient who was taking 0.25 mg of digoxin PO q.d., was administered 12.5 mg of captopril PO t.i.d. for 7 days. The peak serum concentration of digoxin (Cmax) before and after (on Days 0 and 7) captopril administration was 1.7+/-0.2 ng/ml and 2.7+/-0.2 ng/ml, the time to peak (tmax) was 2.4+/-0.5 h and 1.3+/-0.2 h, and the area under the 24-hour digoxin concentration-time curve (AUC0-24h) was 30.0+/-1.5 ng x h/ml and 41.7+/-3.4 ng x h/ml, respectively. While captopril caused a significant increase in peak serum concentration and the area under the digoxin concentration-time curve, it decreased the time to digoxin peak (p = 0.01, p = 0.04, p = 0.01, respectively). No patient developed evidence of digoxin toxicity. Concomitant administration of captopril with digoxin increases serum digoxin concentration in patients with severe congestive heart failure.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Captopril/farmacología , Cardiotónicos/farmacología , Digoxina/farmacocinética , Insuficiencia Cardíaca/tratamiento farmacológico , Administración Oral , Anciano , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Captopril/administración & dosificación , Cardiotónicos/administración & dosificación , Esquema de Medicación , Interacciones Farmacológicas , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
A retrospective study of 1,269 patients on digoxin was done to determine the relationship between serum digoxin levels of 3.0 ng/ml or higher and clinical toxicity. Of 1,269 patients, 58 (4.6%) had digoxin serum levels of 3.0 ng/ml or higher. Clinical evidence of digoxin toxicity was present in only 11 of these patients and premature blood sampling accounted for the high levels in 10 other nontoxic patients. None of the patients with clinical toxicity died. The other 37 patients tolerated the high digoxin levels without exhibiting toxic effect. Low cardiac output, concomitant use of other drugs, and impaired renal function increased the serum digoxin levels in patients with and without clinical toxicity. Appropriate therapeutic digoxin level monitoring and confirmatory laboratory-clinical relationship may have important influences on these results. Additional work on further definition of "toxic" digoxin levels needs to be performed.
Asunto(s)
Antiarrítmicos/efectos adversos , Antiarrítmicos/sangre , Cardiotónicos/efectos adversos , Cardiotónicos/sangre , Digoxina/efectos adversos , Digoxina/sangre , Adulto , Anciano , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Náusea/inducido químicamente , Estudios Retrospectivos , Vómitos/inducido químicamenteRESUMEN
The ability of a nicotine vaccine to protect against nicotine-induced seizures was studied in rats. Groups of 10 rats were vaccinated with 3 doses of either a nicotine conjugate vaccine over 6 weeks to elicit high titers of nicotine-specific antibodies or with a control vaccine. Rats were then pretreated with a 1-week subcutaneous infusion of either nicotine 1 mg/kg/day or saline and then received a single 2 mg/kg ip dose of nicotine to provoke seizures. Vaccination reduced the incidence of seizures. The combination of vaccination and pretreatment with nicotine infusion was more effective than either treatment alone. These data suggest that vaccination is protective against this toxic effect of nicotine and that combining vaccination and chronic nicotine administration may provide a novel strategy for blocking some effects of nicotine.
Asunto(s)
Nicotina/inmunología , Nicotina/farmacología , Agonistas Nicotínicos/inmunología , Agonistas Nicotínicos/farmacología , Antagonistas Nicotínicos/farmacología , Convulsiones/inducido químicamente , Convulsiones/prevención & control , Vacunación , Animales , Encéfalo/metabolismo , Proteínas Portadoras , Ensayo de Inmunoadsorción Enzimática , Haptenos/inmunología , Inmunoglobulina E/sangre , Infusiones Intravenosas , Masculino , Nicotina/administración & dosificación , Agonistas Nicotínicos/administración & dosificación , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: We investigated both the effects of the endothelin type B (ETB) receptor antagonist, BQ-788, on amitriptyline-induced cardiotoxicity and the role of ETB receptors on amitriptyline-induced cardiovascular depression. METHODS: Male Wistar rats were anaesthetized with urethane/chloralose. Mean arterial pressure (MAP), heart rate (HR) and QRS duration were recorded. Toxicity was induced by amitriptyline infusion (0.94 mg/kg per min) until the 50% inhibition of MAP. In the first protocol, 5% dextrose or BQ-788 bolus was administered to control or experimental group animals, respectively. In the second protocol, after incubation with BQ-788 or 5% dextrose, amitriptyline was infused. RESULTS: Amitriptyline caused a significant decrease in MAP, prolonged QRS duration and decreased HR for both the groups. BQ-788 administration improved MAP (5, 10 and 15 min), shortened the prolonged QRS (5 and 10 minutes) and increased HR (5, 10 and 15 min) compared with dextrose group. While all the amitriptyline-infused rats survived in BQ-788 group, all the amitriptyline-infused rats died within 20 min in dextrose group. In the second protocol, BQ-788 incubation did not cause any statistically significant change in amitriptyline-induced cardiovascular depression. CONCLUSION: BQ-788 may have beneficial effects in amitriptyline-induced cardiovascular changes via a physiologic antagonism. ETB receptor antagonists may be the promising antidotes for the cardiovascular toxicity with hypotension and bradycardia.
Asunto(s)
Antídotos/uso terapéutico , Enfermedades Cardiovasculares/tratamiento farmacológico , Antagonistas de los Receptores de la Endotelina B , Oligopéptidos/uso terapéutico , Piperidinas/uso terapéutico , Amitriptilina , Animales , Antídotos/farmacología , Presión Arterial/efectos de los fármacos , Enfermedades Cardiovasculares/inducido químicamente , Enfermedades Cardiovasculares/fisiopatología , Frecuencia Cardíaca/efectos de los fármacos , Masculino , Oligopéptidos/farmacología , Piperidinas/farmacología , Ratas , Ratas WistarRESUMEN
OBJECTIVE: The aim of this study was to analyse the caustic and household detergent exposure cases were admitted to the Department of Emergency Medicine at Dokuz Eylul University Hospital (EMDEU) between 1993 and 2008. METHODS: Age, sex, reason of exposure, clinical signs, rate of endoscopy in oral exposures, treatment attempts, length of hospital stay and outcome were evaluated. A chi-square test was used to analyse statistical differences. RESULTS: Caustic exposures accounted for 8.5% (1160 cases) and 4.1% (1988 cases) of all poisonings in children and adults, respectively. Female/male ratio of caustic exposure poisonings was 0.8. Most of the exposures were unintentional (158, 86.8%). Intentional exposures were common in cases between 19 and 29 years old (χ(2) = 25.685, p < 0.001). The most common caustic substance was alkaline (106, 58.3%) followed by acidic (47, 25.8%) and other household detergents (28, 15.4%). Vomiting (35.7%), nausea (14.8%) and sore throat (13.1%) were the most common clinical signs. The patients who had endoscopy, the most frequent finding was first-degree damage (58.7%). A 48-year-old man died from intentional hydrochloric acid ingestion. CONCLUSION: Because of the large number of unintentional caustic exposures, parent education is very important to decrease the caustic exposures in children.
Asunto(s)
Quemaduras Químicas/epidemiología , Cáusticos/toxicidad , Detergentes/toxicidad , Servicios Médicos de Urgencia/estadística & datos numéricos , Esófago/lesiones , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Quemaduras Químicas/etiología , Niño , Preescolar , Femenino , Humanos , Ácido Clorhídrico/envenenamiento , Lactante , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Turquía/epidemiología , Adulto JovenRESUMEN
Latrodectism is considered dangerous for human beings. Acute renal failure after envenomation is not common and usually results from prerenal failure. We report a 59-y-o man with acute oliguric renal failure due to a combination of prerenal and renal causes after being bitten by a black Latrodectus spider. He had the characteristic anxiety, severe hypertension, tremor, facial edema, and generalized diaphoresis. The patient recovered within a week without sequelae. Clinicians should not overlook the possibility of acute renal failure in latrodectism.
Asunto(s)
Lesión Renal Aguda/etiología , Araña Viuda Negra , Picaduras de Arañas/complicaciones , Venenos de Araña/envenenamiento , Lesión Renal Aguda/patología , Animales , Pruebas de Química Clínica , Pruebas Hematológicas , Humanos , Masculino , Persona de Mediana Edad , Picaduras de Arañas/patologíaRESUMEN
Midazolam is known to cause a dose-dependent increase and decrease in the contractile force of the myocardium. Whether flumazenil can reverse these effects of midazolam remains unclear. In this study, we determined the cardiac effects of midazolam and the counter effect of flumazenil on midazolam-induced myocardial depression in isolated rabbit hearts. Rabbit hearts were isolated and perfused using the Langendorff technique, and left ventricle pressure and heart rate were measured by a pressure transducer in the left ventricle. One set of hearts were perfused with increasing concentrations of midazolam for 10 min, another set were perfused with concomitant midazolam and flumazenil. Concentrations of 5, 10, 20 and 50 microM midazolam decreased left ventricle pressure significantly (P < 0.01, P < 0.05, P < 0.01, P < 0.01, respectively). Heart rates decreased with concentrations of 10, 20 and 50 microM midazolam (P < 0.01, P < 0.01, P < 0.05, respectively). Flumazenil had no effect on the midazolam-induced decrease in left ventricle pressure and heart rate. Midazolam decreased the cardiac contractile force and heart rate of isolated rabbit hearts in a concentration-dependent manner. The failure of flumazenil to reverse these effects suggest that this cardiac depressant effect of midazolam is not mediated through peripheral benzodiazepine receptors.
Asunto(s)
Anestésicos Intravenosos/farmacología , Flumazenil/farmacología , Moduladores del GABA/farmacología , Corazón/efectos de los fármacos , Midazolam/farmacología , Animales , Depresión Química , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Corazón/fisiología , Frecuencia Cardíaca/efectos de los fármacos , Técnicas In Vitro , Masculino , Conejos , Función Ventricular Izquierda/efectos de los fármacos , Presión Ventricular/efectos de los fármacosRESUMEN
A 55 year-old female ingested two bulbs of Urginea maritime (squill) plant as a folk remedy for her arthritic pains. Her past history was significant for Hashimoto thyroiditis and she was hypothyroid upon presentation. Subsequent effects resembling those seen with cardiac glycoside intoxication included nausea, vomiting, seizures, hyperkalemia, atrioventricular block and ventricular arrhythmias resembling digitalis toxicity. A serum digoxin level by an enzyme immunoassay method was 1.59 ng/mL. Despite supportive treatment and pacing, the patient expired from ventricular arrhythmias 30 h after ingestion. Squill has been recognized since antiquity for the clinical toxicity of its cardiac glycosides, but this appears to be the first report of a fatality since 1966.
Asunto(s)
Intoxicación por Plantas/fisiopatología , Plantas Medicinales , Digoxina/sangre , Electrocardiografía , Resultado Fatal , Femenino , Inmunoensayo de Polarización Fluorescente , Lavado Gástrico , Humanos , Medicina Tradicional , Persona de Mediana Edad , Intoxicación por Plantas/terapia , Taquicardia Ventricular/etiología , TurquíaRESUMEN
STUDY OBJECTIVE: To determine whether immediate treatment with oral activated charcoal (AC) products of differing surface areas prevents clinical toxicity of a lethal oral dose of dichlorvos in mice. DESIGN: An in vivo, prospective, randomized, placebo-controlled study using 75 male albino mice. INTERVENTIONS: Fasting mice were administered 57.5 mg/kg of a 0.55% dichlorvos solution via feeding tube. One minute later, groups of 15 mice each received 1 or 2 g/kg of Actidose-Aqua AC or 1 or 2 g/kg of Sigma AC or sterile water by feeding tube. In this way, all mice received 15 mL/kg of an AC suspension or sterile water. The animals were observed for 24 hours for seizures or death. RESULTS: In all treatment groups, mice were found to have significantly fewer seizures and deaths (P < .05) than the control group when compared by chi 2 and Fisher's exact tests. No statistical difference was found between the death and seizure rates when treatment groups were compared with each other. The group sizes were too small, however, to rule out significant type II error (beta > .2). CONCLUSION: In this in vivo mouse model, all AC products tested decreased the incidence of seizures and death. Further studies should be done to investigate the clinical effects of AC products with different surface areas.
Asunto(s)
Carbón Orgánico/uso terapéutico , Diclorvos/toxicidad , Administración Oral , Animales , Masculino , Ratones , Estudios Prospectivos , Distribución Aleatoria , Resultado del TratamientoRESUMEN
OBJECTIVE: To determine the effects of 4-aminopyridine and Bay K 8644 on mean arterial pressure and heart rate in an anesthetized rat model of verapamil toxicity. METHODS: The study was a randomized, controlled animal study. Rats were anesthetized and the carotid artery was cannulated for mean arterial pressure and heart rate measurements while both jugular veins were cannulated for drug administration. All animals were infused with verapamil (15 mg/kg/h i.v.) until 45-60% reduction of mean arterial pressure and 30% reduction of heart rate were observed. After verapamil, control animals were given normal saline solution and the other groups received 4-aminopyridine (1 and 2 mg/kg/h) or Bay K 8644 (0.3 and 0.6 mg/kg/h) for 60 minutes. RESULTS: While 4-aminopyridine (1 mg/kg/h i.v.) did not significantly increase mean arterial pressure (75.9 +/- 5.5%) when compared with the control group (64.3 +/- 5.1%, p > 0.05), 2 mg/kg/h i.v. of 4-aminopyridine improved mean arterial pressure within 40 minutes (87.4 +/- 6.6%, p < 0.05, 95% CI 66.4-108.6%). Because the 2 mg/kg/h 4-aminopyridine produced side effects including seizures, secretions, and fasciculations at 35 +/- 5 minutes, the infusion was stopped at that time. Only the 2 mg/kg/h 4-aminopyridine infusion increased the heart rate at 10 and 20 minutes compared with the control group (p < 0.05, 95% CI 283.2-364.4). Bay K 8644 (0.3 and 0.6 mg/kg/h i.v.) significantly enhanced mean arterial pressure within 5 minutes (68.0 +/- 4.1% and 73.0 +/- 2.9%, respectively, p < 0.05), (95% CI 56.8-78.0% and 95% CI 64.9-81.1%, respectively) but no significant changes in mean arterial pressure were observed after 5 minutes. The 4-aminopyridine (2 mg/kg/h) increased the heart rate at 10 and 20 minutes compared with the control group (p < 0.05, 95% CI 311.3-358.7). Bay K 8644 did not produce a significant effect on heart rate (p > 0.05). CONCLUSIONS: 4-Aminopyridine improved mean arterial pressure and heart rate in a dose-dependent fashion; however, the higher infusion rate (2 mg/kg/h) necessary to improve mean arterial pressure and heart rate resulted in convulsions and excessive secretions. The reversal effects of Bay K 8644 on mean arterial pressure were transient and did not affect heart rate.
Asunto(s)
Ácido 3-piridinacarboxílico, 1,4-dihidro-2,6-dimetil-5-nitro-4-(2-(trifluorometil)fenil)-, Éster Metílico/farmacología , 4-Aminopiridina/farmacología , Agonistas de los Canales de Calcio/farmacología , Bloqueadores de los Canales de Calcio/toxicidad , Sistema Cardiovascular/efectos de los fármacos , Verapamilo/toxicidad , Animales , Presión Sanguínea/efectos de los fármacos , Bradicardia/inducido químicamente , Bradicardia/tratamiento farmacológico , Relación Dosis-Respuesta a Droga , Frecuencia Cardíaca/efectos de los fármacos , Hipotensión/inducido químicamente , Hipotensión/tratamiento farmacológico , Masculino , Distribución Aleatoria , Ratas , Ratas WistarRESUMEN
A 54-y-o woman presented to the Emergency Department with shortness of breath and sore throat after intranasal administration of Ecbalium elaterium as a folk remedy for her sinusitis. The patient's history included nasal aspiration of the juice of the squirting cucumber (Ecbalium elaterium) for acute maxillary sinusitis. An airway obstruction due to severe uvular angioedema was detected and confirmed by airway X-ray. The patient was treated with 100% oxygen with mask, 0.3 mg epinephrine s.c., and 80 mg prednisolone i.v. Renal and hepatic function tests were normal. After a 24-h observation, the patient was discharged in her previous state of health.