RESUMEN
Since six decades, Isoniazid and Rifampicin are used as first line drugs for treatment of tuberculosis. The minimum acute lethal or toxic dose of Rifampicin is not well established. However, non-fatal acute overdoses in adults have been reported with doses ranging from 9 to 12 gm and fatal acute overdoses with doses ranging from 14 to 60 gm. Isoniazid, if acutely ingested, even 1.5 to 2 gram may cause toxicity in adults. We report a case of Pott's spine on ATT, who took massive overdose of Rifampicin (>18 gm) and Isoniazid (>12 gm) and reported late (almost 36 hours) after ingestion. He was treated successfully with pyridoxine, hemodialysis and supportive care.
Asunto(s)
Antituberculosos/envenenamiento , Sobredosis de Droga/complicaciones , Isoniazida/envenenamiento , Rifampin/envenenamiento , Tuberculosis de la Columna Vertebral/tratamiento farmacológico , Adulto , Humanos , Masculino , Índice de Severidad de la EnfermedadAsunto(s)
Antituberculosos/envenenamiento , Isoniazida/envenenamiento , Piridoxina/administración & dosificación , Convulsiones/tratamiento farmacológico , Complejo Vitamínico B/administración & dosificación , Administración Intravenosa , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Centros de Control de Intoxicaciones/estadística & datos numéricos , Estudios Retrospectivos , Convulsiones/inducido químicamente , Factores de Tiempo , Adulto JovenRESUMEN
A 19-years old, previously healthy male, ingested the higher amount of rifampicin, isoniazyd, pyrazinamide, ketoprofene and alcohol. Within less than 20 hours he developed dyspnoe, pruritus, red man syndrome, and ECG changes suggesting acute coronary syndrome appeared - ST interval elevation. In the next few hours chest pain appeared and troponin I concentration was elevated (13.54 ng/ml). The performed echocardiography revealed global hypokinesis with the decreased left ventricular ejection fraction (approx. 30%). There was no significant pathological changes in coronarography, except for slowed blood flow. Further patient developed cardiogenic shock, pulmonary oedema and died within 32 hours from medication overdose.
Asunto(s)
Síndrome Coronario Agudo/inducido químicamente , Síndrome Coronario Agudo/diagnóstico , Antituberculosos/envenenamiento , Sobredosis de Droga/complicaciones , Sobredosis de Droga/diagnóstico , Suicidio , Ecocardiografía , Etanol/envenenamiento , Resultado Fatal , Humanos , Isoniazida/envenenamiento , Cetoprofeno/envenenamiento , Masculino , Pirazinamida/envenenamiento , Rifampin/envenenamiento , Choque Cardiogénico/inducido químicamente , Choque Cardiogénico/diagnóstico , Adulto JovenRESUMEN
Ethambutol is a commonly used first-line anti-tuberculosis agent, and its most important potential side-effect is ethambutol-induced optic neuropathy (EON). Understanding of the incidence,clinical characteristics, risk factors, prognosis and mechanism of EON is of practical significance in the diagnosis and treatment of this disorder. This article reviews the present status of these aspects.
Asunto(s)
Antituberculosos/envenenamiento , Etambutol/envenenamiento , Enfermedades del Nervio Óptico/inducido químicamente , HumanosRESUMEN
BACKGROUND: Isoniazid (INH) is an effective treatment for tuberculosis and among the most common causes of drug-induced seizures in the United States. Isoniazid intoxication produces a characteristic clinical syndrome including seizures, metabolic acidosis, and, in severe cases, respiratory depression and coma. CASE: A 10-month-old male infant was presented after being found with his father's INH. The patient was brought to a local hospital where he had a witnessed generalized seizure and was given 650 mg pyridoxine intravenously, which was based on a 70 mg/kg recommendation. Five hours after the time of ingestion, the patient developed recurrent generalized seizures. He was given diazepam and then loaded with phenobarbital 20 mg/kg, while awaiting more pyridoxine from the pharmacy. He received an additional 2 g pyridoxine for a suspected ingestion of approximately 2.7 g INH (290 mg/kg total dose), and his seizures subsequently resolved. DISCUSSION: Treatment of INH toxicity must address correction of gamma-aminobutyric acid deficiency with pyridoxine replacement and management of life-threatening events. For poisonings in which the amount of INH ingested is known, pyridoxine is dosed on a gram-for-gram basis. Several reference textbooks recommend pyridoxine dosing in children to be 70 mg/kg. This was the justification for the initial pyridoxine dose administered in our case. However, after review of the referenced literature, the rationale supporting this recommendation remains unclear. Benzodiazepines should also be given with pyridoxine as they have been shown to have a synergistic effect in terminating seizures in animal models. CONCLUSIONS: As soon as possible after INH overdose is suspected or diagnosed, pyridoxine should be administered in a dose approximately equal to the estimated amount of INH ingested regardless of the age of the patient.
Asunto(s)
Antituberculosos/envenenamiento , Isoniazida/envenenamiento , Piridoxina/administración & dosificación , Estado Epiléptico/inducido químicamente , Complejo Vitamínico B/administración & dosificación , Diagnóstico Diferencial , Relación Dosis-Respuesta a Droga , Sobredosis de Droga , Humanos , Lactante , Infusiones Intravenosas , Masculino , Piridoxina/efectos adversos , Estado Epiléptico/diagnóstico , Estado Epiléptico/tratamiento farmacológico , Complejo Vitamínico B/efectos adversosRESUMEN
Accidental or intentional Isoniazid poisoning may manifest within half to three hours as intractable seizure, acidosis, and coma. Single high dose of pyridoxine was used as an antidote with good response as reported earlier. Ingestion of more than 80 mg/kg body weight produces severe central nervous system symptoms and a dose of 125 mg/kg is potentially lethal if not promptly treated. We report a case of suicidal attempt with use of Isoniazid, who developed grand mal seizures and was controlled with diazepam and symptomatic treatment.
Asunto(s)
Antituberculosos/envenenamiento , Sobredosis de Droga/tratamiento farmacológico , Isoniazida/envenenamiento , Intento de Suicidio , Adulto , Antieméticos/uso terapéutico , Diazepam/uso terapéutico , Epilepsia Tónico-Clónica/tratamiento farmacológico , Epilepsia Tónico-Clónica/etiología , Femenino , Humanos , Piridoxina/uso terapéutico , Complejo Vitamínico B/uso terapéuticoRESUMEN
We present a case report describing outcomes in a 21 year old HIV-negative man who received treatment with bedaquiline. Due to error, dosage received comprised 4 pills of 100 mg every second day in the 60 days following the first two weeks of 4 pills of 100 mg every day. On detection, treatment was continued as per standard dosing of 200 mg given three times per week, with enhanced monitoring of ECG and liver function. The man was asymptomatic, with no signs of jaundice, abdominal pain, or abnormal heart rhythm. Toxic effects at this dosage were therefore not observed.
Asunto(s)
Antituberculosos/envenenamiento , Diarilquinolinas/envenenamiento , Sobredosis de Droga , Humanos , Masculino , Adulto JovenRESUMEN
Isoniazid is widely used to treat tuberculosis. In populations with a high prevalence rate of tuberculosis, acute ingestion of isoniazid has been reported as a potential cause of coma. In this study, we present the diagnosis and treatment of isoniazid poisoning in a case with acute coma as the major clinical presentation.A 32-year-old male who ingested 12 g isoniazid (2 hours prior to medical attention) was brought to the emergency department while in a coma and experiencing frequent seizures. Initial treatment with large doses of pyridoxine (for 6 hours) failed to awaken this patient. The patient was then given hemodialysis and pyridoxine; after 3 days he awoke from coma, with no further reported seizures.Isoniazid poisoning should be suspected in patients whose major symptoms are coma and seizure, especially those who have access to isoniazid. Monitoring the blood level of isoniazid will establish the diagnosis and help clinical management. A combination of hemodialysis and pyridoxine is effective in treating isoniazid poisoning.
Asunto(s)
Antituberculosos/envenenamiento , Coma/etiología , Isoniazida/envenenamiento , Piridoxina/uso terapéutico , Complejo Vitamínico B/uso terapéutico , Adulto , Coma/terapia , Humanos , Masculino , Diálisis Renal , Intento de SuicidioRESUMEN
BACKGROUND: Fixed drug combination of isoniazid and rifampicin is a rare cause of poisoning even in endemic countries for tuberculosis infection. Severe poisoning can cause severe morbidity and mortality if not treated promptly. Though intravenous pyridoxine is the preferred antidote for severe standard isoniazid poisoning it is not freely available even in best of care centers. We describe a case of severe poisoning with fixed drug combination of isoniazid and rifampicin successfully managed with oral pyridoxine at national hospital of Sri Lanka. CASE PRESENTATION: A 22 year old, Sri Lankan female presented to a local hospital 1 h after self-ingestion of 28 tablets of fixed drug combination of isoniazid and rifampicin which contained 4.2 g of standard isoniazid and 7.2 g of rifampicin. One and half hours after ingestion she developed generalized tonic-clonic seizure with loss of consciousness. She was given intravenous diazepam 5 mg immediately and transferred to national hospital of Sri Lanka, for further care. Upon arrival to tertiary care hospital in 3.5 h of poisoning she had persistent vomiting, dizziness and headache. On examination, she was drowsy but arousable, orange-red discoloration of the body was noted even with the dark skin complexion. She also had orange-red colour urine and vomitus. Pulse rate was 104 beats/min, blood pressure 130/80 mmHg, respiratory rate was 20 breaths/min. The arterial blood gas analysis revealed compensated metabolic acidosis and mildly elevated lactic acid level. Considering the clinical presentation with neurological toxicity and the large amount of isoniazid dose ingested, crushed oral tablets of pyridoxine 4.2 g (equal to standard isoniazid dose ingested) administered immediately via a nasogastric tube since intravenous preparation was not available in the hospital. Simultaneously forced diuresis using intravenous 0.9% saline was commenced in order to enhance excretion of toxic metabolites via kidneys. She had no recurrence of seizures but had acute liver injury subsequently which gradually improved with supportive care. Her liver functions found to be completely normal 1 week after the discharge. CONCLUSIONS: Poisoning with fixed drug combination of isoniazid and rifampicin tablets is rare but can cause severe morbidity and mortality if not treated promptly. Oral pyridoxine can substitute for intravenous pyridoxine with almost similar efficacy at a low cost in managing patients with acute severe standard isoniazid poisoning in resource poor setting.
Asunto(s)
Antídotos/administración & dosificación , Antituberculosos/envenenamiento , Isoniazida/envenenamiento , Piridoxina/administración & dosificación , Rifampin/envenenamiento , Convulsiones/prevención & control , Inconsciencia/tratamiento farmacológico , Administración Oral , Diazepam/administración & dosificación , Combinación de Medicamentos , Femenino , Humanos , Convulsiones/inducido químicamente , Convulsiones/metabolismo , Convulsiones/fisiopatología , Sri Lanka , Intento de Suicidio , Comprimidos , Resultado del Tratamiento , Inconsciencia/inducido químicamente , Inconsciencia/metabolismo , Inconsciencia/fisiopatología , Adulto JovenRESUMEN
A 25-year-old, 54-kg Hispanic man who had recently started multidrug therapy for pulmonary tuberculosis presented in status epilepticus after ingesting 9 g of isoniazid in a suicide attempt. Successful management of this patient required collaboration between several institutions to provide the large amount of necessary intravenous pyridoxine. Ultimately, this single overdose depleted the supply of intravenous pyridoxine for a significant region of the state of Nebraska. Isoniazid is commonly used to treat tuberculosis, but it is encountered relatively infrequently as the cause of an acute overdose. Severe isoniazid overdoses may present as seizure activity that is refractory to conventional antiepileptic therapy. Although intravenous pyridoxine is an effective antidote for isoniazid overdoses in patients presenting with status epilepticus, this agent has few indications and is typically stocked in limited quantities. In regions with large populations of patients who receive antituberculosis therapy, collaborative networks must be created to ensure that adequate supplies of intravenous pyridoxine (> or = 20 g) are available for effective treatment of isoniazid poisonings.
Asunto(s)
Antituberculosos/envenenamiento , Sobredosis de Droga , Isoniazida/envenenamiento , Piridoxina/uso terapéutico , Estado Epiléptico/tratamiento farmacológico , Intento de Suicidio , Enfermedad Aguda , Adulto , Antídotos/provisión & distribución , Medicamentos Esenciales/administración & dosificación , Medicamentos Esenciales/provisión & distribución , Humanos , Infusiones Intravenosas , Masculino , Nebraska , Piridoxina/administración & dosificación , Piridoxina/provisión & distribución , Estado Epiléptico/inducido químicamente , Tuberculosis Pulmonar/tratamiento farmacológicoRESUMEN
BACKGROUND: Because increased hepatotoxicity was observed with first line antituberculous agents using four drug standard induction therapy in orthotopic liver transplant patients, we evaluated the efficacy and adverse effects of a novel continuation regimen for the treatment of tuberculosis in orthotopic liver transplant patients at a University Hospital in New York City. METHODS: The hospital records of all patients who were referred to Mount Sinai Hospital (n=924) and who underwent orthotopic liver transplant between September 1988 and May 1998 were reviewed. Data were collected from patient records. Nine orthotopic liver transplant patients (0.97%) developed tuberculosis over a 9.5-year period. A total of seven of nine (78%) patients had disseminated tuberculosis including two patients with meningitis. All mycobacterial isolates were sensitive to isoniazid, rifampin, pyrazinamide, and ethambutol. Standard induction therapy with three or four drugs was given for 2 months (mean). Hepatotoxicity related to the standard induction regimen developed in five of six (83.3%) patients. Liver biopsy during induction therapy revealed drug induced hepatitis in five of six (88%) patients and rejection in three of six (50%) patients. Continuation regimens consisted mainly of ethambutol and ofloxacin; mean length of therapy 9 months. RESULTS: Overall mortality was 33.3% (three of nine patients) over a 4.5-year follow-up period. Tuberculosis associated mortality was 22.2%. One patient died before therapy, another died with concomitant bacterial sepsis during induction therapy. Six of seven patients are alive and disease free. One patient died of recurrent hepatitis C and graft failure without evidence of tuberculous infection at death. Another patient retransplanted for chronic rejection, remains disease free at 1 year. The mean follow-up for six patients that completed treatment was 3.75 years (2.5-5.3 years). Six patients are free of tuberculosis. CONCLUSIONS: Our experience reveals that orthotopic liver transplant patients have poor tolerance for conventional therapy due to inherent toxicity of these agents and their concomitant bouts of organ rejection. Our nonconventional therapy yielded remarkably good results in that six patients, all with disseminated disease, were well after mean 3.5 years of follow-up. Consideration should be given to this novel follow-up therapy in patients without cavitary pulmonary disease who develop hepatotoxicity during induction.
Asunto(s)
Antituberculosos/envenenamiento , Antituberculosos/uso terapéutico , Trasplante de Hígado , Hígado/efectos de los fármacos , Complicaciones Posoperatorias , Tuberculosis/tratamiento farmacológico , Tuberculosis/etiología , Adulto , Anciano , Enfermedad Hepática Inducida por Sustancias y Drogas , Quimioterapia Combinada , Etambutol/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ofloxacino/uso terapéutico , Retratamiento , Resultado del Tratamiento , Tuberculosis/mortalidadRESUMEN
OBJECTIVES: To review the pathophysiology, presentation and treatment of isoniazid (INH) intoxication. DATA SOURCES: Human, animal and modeling studies published since 1940 identified through MEDLINE and a review of the bibliographies of relevant articles. STUDY SELECTION AND DATA EXTRACTION: The studies identified were reviewed with emphasis on the most recent. Earlier studies were selected for their historical value and relevance to the clinical setting. DATA SYNTHESIS: Isoniazid overdose is a potentially fatal intoxication. The incidence of tuberculosis has recently increased in the United States and therefore the frequency of INH overdose may also increase. Patients with INH overdose may present with nausea, vomiting, ataxia, symptoms reminiscent of atropine intoxication, coma and grand mal seizures. Lactic acidosis is revealed by laboratory evaluation. Treatment requires admission to the ICU for ventilatory support, and management of seizures and acid-base abnormalities. Pyridoxine, in a dose equivalent to the amount of INH ingested, is the only effective antidote. CONCLUSIONS: INH overdose should be suspected in any patient presenting with seizures and metabolic acidosis. Prognosis is good when treatment is instituted early.
Asunto(s)
Antituberculosos/envenenamiento , Isoniazida/envenenamiento , Acidosis/etiología , Acidosis/metabolismo , Adolescente , Adulto , Antituberculosos/farmacología , Sobredosis de Droga , Femenino , Humanos , Isoniazida/farmacología , Masculino , Pronóstico , Piridoxina/administración & dosificación , Piridoxina/efectos adversos , Piridoxina/uso terapéutico , Convulsiones/tratamiento farmacológico , Convulsiones/etiologíaRESUMEN
A previously healthy 2-year-old girl was admitted with generalized convulsive status epilepticus. She was in a stupor and could respond only to painful stimuli. She also had severe metabolic acidosis. Although initial liver function tests were normal, they were found to be moderately high on the fifth day of admission; however, they dropped to their normal ranges on the twelfth day of admission. Initially, the patient was diagnosed as having idiopathic status epilepticus, and classic anticonvulsant agents, including diazepam, phenytoin, and then phenobarbital, were given. However, her seizures did not subside, and diazepam infusion was initiated. After initiation of diazepam infusion, the seizures were completely controlled. On the fourth day of admission, her parents said that she had accidentally received 20 tablets (a total dose of 2000 mg) of isoniazid just before admission to our hospital. Later, we injected 200 mg of pyridoxine intravenously. During follow-up, her general condition improved, and anticonvulsant agents were discontinued because an electroencephalogram was found to be norma. She was discharged from the hospital on the twelfth day of admission. At the fourth month of follow-up, she was seizure free. Because of this case, we would like to re-emphasize that acute isoniazid poisoning should also be considered in a child with unexplained status epilepticus.
Asunto(s)
Antituberculosos/envenenamiento , Isoniazida/envenenamiento , Estado Epiléptico/inducido químicamente , Acidosis/inducido químicamente , Preescolar , Diagnóstico Diferencial , Diazepam/uso terapéutico , Sobredosis de Droga/diagnóstico , Electroencefalografía , Femenino , Humanos , Piridoxina/uso terapéutico , Estado Epiléptico/tratamiento farmacológico , Resultado del TratamientoRESUMEN
We identified 41 New York City residents who had been hospitalized at least overnight between January 1992 and September 1993 because of a toxic isoniazid (INH) exposure. Review of the available medical charts of 33 patients revealed that median age was 19 years, 27 (82%) were females, and 24 (83%) were taking INH chemoprophylaxis for tuberculosis infection. Twenty-two patients had seizures. Twenty-seven (82%) patients had attempted suicide using INH, and another three patients had intentionally misused INH by making up missed doses at one time. All patients survived. Physicians should be aware of the potential for INH toxicity and should assess their patients' current mental and psychosocial status when prescribing it. INH toxicity should be considered when young patients, particularly females, present with unexplained intractable seizures, and treatment with pyridoxine should be given.
Asunto(s)
Antituberculosos/envenenamiento , Isoniazida/envenenamiento , Intoxicación/epidemiología , Adolescente , Adulto , Distribución por Edad , Niño , Preescolar , Sobredosis de Droga/epidemiología , Sobredosis de Droga/etiología , Servicio de Urgencia en Hospital , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Ciudad de Nueva York/epidemiología , Distribución por Sexo , Intento de Suicidio/estadística & datos numéricos , Tasa de Supervivencia , Tuberculosis/tratamiento farmacológicoRESUMEN
Isoniazid (INH) is widely used in most prophylactic and therapeutic anti-tuberculosis regimens because of its effectiveness and low cost. Yet, INH poisoning appears to be rare. We report the first case of intentional INH overdosage in Singapore. A 26-year-old Filipino male presented with mental obtundation, recurrent seizures, metabolic acidosis and hepatic dysfunction. He was successfully treated with large doses of pyridoxine (vitamin B6). Recommendations for the management of acute INH toxicity are highlighted.
Asunto(s)
Antituberculosos/envenenamiento , Isoniazida/envenenamiento , Intento de Suicidio , Adulto , Antituberculosos/uso terapéutico , Sobredosis de Droga/diagnóstico , Sobredosis de Droga/fisiopatología , Humanos , Isoniazida/uso terapéutico , Masculino , Tuberculosis Pulmonar/tratamiento farmacológicoRESUMEN
A case of young female who was brought in status epilepticus with history of isoniazid poisoning is discussed. Early institution of treatment with pyridoxine saves the patient's life.
Asunto(s)
Antituberculosos/envenenamiento , Isoniazida/envenenamiento , Estado Epiléptico/inducido químicamente , Intento de Suicidio , Adulto , Supervivencia sin Enfermedad , Femenino , Humanos , Tuberculosis/tratamiento farmacológicoRESUMEN
Acute isoniazid (INH) poisoning is uncommon in children. Although most physicians are aware of INH hepatotoxicity, acute INH poisoning and its treatment are not well recognized. INH is increasingly being used to control the spread of tuberculosis, and physicians should know its potentially fatal effects. INH overdose is known to result in rapid onset of seizures, metabolic acidosis and prolonged obtundation. We report two cases of obtundation secondary to INH overdose that was immediately reversed by pyridoxine. Parenteral pyridoxine administration is an effective method in INH intoxication. The intravenous form of pyridoxine must be available in the emergency care units, and INH toxicity should be suspected in any patient with refractory seizures and metabolic acidosis.
Asunto(s)
Antituberculosos/envenenamiento , Epilepsia Tónico-Clónica/inducido químicamente , Isoniazida/envenenamiento , Convulsiones/inducido químicamente , Adolescente , Sobredosis de Droga , Femenino , Humanos , Lactante , Masculino , Piridoxina/uso terapéuticoRESUMEN
A young girl was admitted with generalized tonic clonic seizures and unconsciousness, four hours after ingestion of 12 gm of isoniazid (INH). In the absence of injectable preparation of pyridoxine, she was treated with oral pyridoxine and made a complete recovery.
Asunto(s)
Antituberculosos/envenenamiento , Isoniazida/envenenamiento , Adulto , Femenino , Humanos , Intoxicación/diagnóstico , Intoxicación/terapiaRESUMEN
It has been established in experiments on white rats that prolonged (for 2 weeks) intoxication with antituberculous drugs (isoniazid plus rifampicin plus pyrazinamide) results in cytolytic liver injury. This manifests by hyperaminotransferasemia, initiation of lipid peroxidation, suppression of the antioxidant system and bile production. Daily injections of tocopherol acetate (15 mg/kg) and riboxine (100 mg/kg) together with administration of antituberculous drugs reduce their hepatotoxicity. The combined use of these hepatoprotectors and antioxidants provides a dramatic increase of their efficacy in durable intoxication with antituberculous drugs.