반복적인 경련을 동반한 아이소니아지드(Isoniazid) 중독환자의 치험 1례

이환,오동렬,정시경,김영민,이운정,김세경,이원재,최경호 大韓應急醫學會 1999 대한응급의학회지 Vol.10 No.2

Isoniazid(Isonicotinic acid hydrazide) is an antimicrobial drug used since 1952 as a first line agent for the prophylaxis and treatment of tuberculosis. Isoniazid is well known for problems in population having a high prevalence of isoniazid use for prophylaxis or treatment of tuberculosis. But intentional or accidental isoniazid overdose is uncommon. The ingestion of toxic amounts of isoniazid causes recurrent seizures, profound metabolic acidosis, coma and even death. In adults, toxicity can occur with the acute ingestion of as little as 1.5g of isoniazid. Doses larger than 30mg per kg often produce seizures. When ingested in amounts of 80-150mg per kg or more, isoniazid can be rapid fatal. 40-year-old woman having previous pulmonary tuberculosis ingested 7gram of isoniazid(140mg/kg) to attempt suicide approximately 30 minutes prior to visit to our emergency medical center. She had recurrent generalized tonicclonic seizures and metabolic acidosis. We report one patient treated with pyridoxine, which was equivalent to the amount of isoniazid ingested and administered as a intravenous dose and oral dose

Isoniazid에 의한 가성용종을 동반한 급성췌장염

차병효 ( Byung Hyo Cha ),이상협 ( Sang Hyub Lee ),황진혁 ( Jin Hyeok Hwang ),김장언 ( Jang Eon Kim ),이상진 ( Sang Jin Lee ),이충식 ( Chung Sik Lee ),김현 ( Hyun Kim ) 대한내과학회 2012 대한내과학회지 Vol.82 No.5

Numerous medications have the potential to induce acute pancreatitis. However, isoniazid-induced acute pancreatitis is extremely rare. Drug-induced acute pancreatitis can be diagnosed by improvement after stopping the drug and recurrence of pancreatitis when rechallenged. We present a case of severe acute pancreatitis accompanied by multiple large pseudocysts after isoniazid treatment for pulmonary tuberculosis. We confirmed that isoniazid induced pancreatitis by rechallenging after treatment cessation. Most previous reports of isoniazid-induced pancreatitis have been clinically mild forms, and the patient fully recovered with supportive management. However, this case presents severe and permanent pancreatic damage that developed with 5 weeks of isoniazid treatment. When a patient presents with manifestations of pancreatitis during treatment of tuberculosis that includes isoniazid, the physician should consider isoniazid-induced pancreatitis. (Korean J Med 2012;82:594-598)

Pyrosequencing 분석법을 이용한 Rifampicin과 Isoniazid 결핵약제내성의 빠른 검사법

오서영 ( Seo Young Oh ),김효빈 ( Hyo Bin Kim ),신민식 ( Min Sik Shin ),김진욱 ( Jin Wook Kim ),박성휘 ( Sung Hwuy Park ) 대한임상검사과학회 2009 대한임상검사과학회지(KJCLS) Vol.41 No.1

Rifampicin (RIF) and isoniazid (INH) are the most important drug for the treatment of Mycobacterium tuberculosis. Mutations correlated to rifampicin and isoniazid-resistance have been detected in rpoB gene and katG gene, respectively. Of the rifampicin-resistant isolates, 90% showed mutations in rpoB gene at codon 507 to 533. Isoniazid-resistant isolates analysed had a mutation in katG at codon 315. The aim of this study is to develop a pyrosequencing-based approach for rapid detection of ripampin or isoniazid resistant M. tuberculosis based on characterization of all possible mutation in the target region. For this study, the DNA selected from 35 cases of MTB PCR positive clinical sample such as bronchial washing, sputum, and pleural fluid. RIF or INH resistant was analyzed by pyrosequencing data of rpoB and katG gene. 28 (80%) and 7 (20%) of 35 MTB PCR positive DNAs were occured rifampicin-sensitivity and resistant, respectively. For INH, 30 (85.7%) and 5 (14.5%) cases were detected isoniazid-sensitivity and resistant, respectively. When pyrosequencing analysis was compared with ABI sequencing analysis, both analysis were presented same result, but pyrosequencing analysis was more rapid than ABI sequencing analysis. In conclusion, we found that pyrosequencing technology offers high accuracy, specificity, short turn around time and a high throughput in detection of rifampicin or isoniazid resistance in M. tuberculosis.

Pyrosequencing 분석법을 이용한 rifampin and isoniazid 항 결핵약제내성의 빠른 검사법

오서영,김효빈,신민식,김진욱,박성휘 대한임상병리사협회 2007 조직세포검사학회 발표자료집 Vol.2007 No.-

결핵 치료의 기본은 항 결핵제를 사용하는 화학요법이다. Rifampin(RIF)과 isoniazid(INH)은 결핵치료를 위한 중요한 약제 중에 하나이며 이 약제의 내성은 결핵균이 가지고 있는 rpoB gene과 katG gene에 돌연변이(mutation)가 나타난다. rifampin(RIF) 약제내성 은 rpoB gene의 amino acid 507-533 region에서 90% 이상의 돌연변이가 일어나며 isoniazid(INH) 약제 내성은 katG gene의 amino acid 315에서 대부분 Ser315Thr 돌연변이가 나타나고 있다. 최근 결핵관리 지침서에는 약제 내성 환자들이 늘어 항 결핵약제 치료시 초기에 약제 내성 검사를 실시하여 효과적인 결핵 약제를 사용하여 조기에 치료하는 것이 좋다고 밝혔다. 이번 연구에서는 Pyrosequencing 법은 20bp-70bp정도의 짧은 서열을 빠른 방법으로 정확하게 서열을 분석 할 수 있다는 장점을 이용하여 Rifampin(RIF)과 isoniazid(INH) 약제 결핵 내성에 관련되는 돌연변이를 빨리 검출 할 수 있는 검사 방법에 대해 연구하였다. 본 연구는 건국대학교병원 호흡기 알레르기 내과에서 의뢰한 검체로 TB PCR 양성을 보인 35명의 환자DNA를 이용하여 결핵약제 내성에 맞는 primer를 제작하고 PCR로 증폭 시킨 후 pyrosequencing을 이용하여 분석하였다. 35명의 항 결핵약제내성 검사에서 rifampin약제에 감수성을 나타낸 환자가 80%로 가장 많고 그 중 ripampin약제 내성으로 나온 환자는 35명 중 7명으로 20% 의 약제내성이 나타나는 것을 확인 할 수 있었고 isoniazid약제내성 검사에서는 isoniazid약제 감수성을 나타낸 환자가 85.7%로 가장 많고 isoniazid약제 내성으로 나온 환자는 35명 중 5명으로 14.3% 의 약제내성이 나타나는 것을 확인 할 수 있었으며 pyrosequencing을 이용한 분석이 다른 결핵약제 내성 검사보다 빠르고 정확한 결과를 나타내었다. 이번 연구에 따르면, pyrosequencing 분석방법을 항 결핵약제내성 검사에 활용이 된다면 결핵환자에게 투여 할 약제의 선택이 용이해지고 보다 정확하고 신속한 항생제 치료를 함으로써 결핵환자에게는 항생제에 대한 고통을 덜어주며 항생제 과잉처방을 줄일 수 있는 계기가 될 것으로 기대되고 있다.

Isoniazid를 포함한 항결핵약제 투여 후 발생한 여성형 유방 증례

허은영 ( Eun Young Heo ),정인아 ( In A Jeong ),이재석 ( Jae Seok Lee ),이창훈 ( Chang Hoon Lee ),정희순 ( Hee Soon Chung ),김덕겸 ( Deog Kyeom Kim ) 대한결핵 및 호흡기학회 2008 Tuberculosis and Respiratory Diseases Vol.65 No.4

Gynecomastia is a benign enlargement of the male breast attributable to proliferation of the ductal elements. Gynecomastia has been rarely reported as an adverse effect of isoniazid therapy. We report the case of a 35-year-old man who was prescribed with isoniazid, rifampicin, ethambutol and pyrazinamide to treat pulmonary and lymphatic tuberculosis. After five months of treatment, the patient complained of painful engorgement in the bilateral breasts and the presence of male gynecomastia was confirmed with a physical examination and radiographical methods. The serum level of estradiol was also increased. Common causes of male gynecomastia were excluded through history taking and the laboratory findings. The anti-TB drugs were changed to a second line regimen due to radiographical progression and the intolerance of the patient to gynecomastia. Gynecomastia was relieved very slowly and a tender subareolar palpable mass decreased in size and consistency over five-month period after stopping the probable causative drug, isoniazid. From a review of the literature, gynecomastia has been shown to be a side effect of treatment with first line anti-tuberculosis drugs, and especially with isoniazid. We report the rare case. (Tuberc Respir Dis 2008;65:308-312)

Isoniazid와 Nitrofurantoin으로 유발되는 간 세포독성에 대한 식물추출물의 보호효과

변에리사,정길생,리빈,양숙현,범진선,이동성,려혜자,안인파,김윤철 한국생약학회 2009 생약학회지 Vol.40 No.2

Isoniazid was discovered in 1950’s and since then it has been widely used as a synthetic bactericidal agent in the treatment of tuberculosis. However, the adverse effect of isoniazid has been reported to show significant hepatotoxicity in approximately 1-2% of patients. Nitrofurantoin {1-(5-nitro-2-furfurylideneamino)-hydantoin} is a synthetic nitrofuran that is commonly used for the treatment and prophylaxis of urinary tract infections, but its use is associated with liver cirrhosis and fatal liver necrosis. Therefore, studies for natural products with protective effect on the isoniazid- and/or nitrofurantoin-in duced hepatotoxcity would be valuable as the potential therapeutic use. 107 plants sources were collected at Mt. Baekdu, and extracte d with methanol. These extracts had been screened for the protective effects against isoniazid- and/or nitrofurantoin-induced cyt otoxicity in HepG2 cells at the both 100 and 300 µg/ml. Five methanolic extracts, Acanthopanax senticosus, Acer mono, Asparagus schoberioides, Fagopyrum tataricum, Potentilla centigrana, showed significant protective effects against isoniazidinduced hepatotoxicity. Two methanolic extracts, Acer mono and Leonurus artemisia, showed significant protective effects against nitrofurantoin-induced cytotoxicity in HepG2 cells.

Protective Effects of White Tea (Camellia Sinensis) on Metabolic Functions and Oxidative Stress in Isoniazid-Induced Hepatotoxic Rat Model

( Rahul Kumar ),( Sagar Verma ) 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: Oxidative stress and hyperlipidemia are associated risk factors for developing liver disease. White tea (WT) is very similar to green tea (GT) but it is exceptionally prepared only from the buds and young tea leaves of Camelia sinensis plant while GT is prepared from the matured tea leaves. Camellia sinensis is a well-known medicinal plant that has been used for its anti-cancer, neuroprotective, and hepatoprotective effects. This study aimed at investigating the hepatoprotective role of ethanolic extract of WT against isoniazid-induced hepatotoxicity in female albino rats. Methods: Wistar rats (n=8 per group)were divided into four groups: saline-treated control, saline-treated control with WT extract (200 mg/kg), isoniazid treatment alone (100 mg/kg, intraperitoneal [i.p.]), and isoniazid-WT extract (200mg/kg) administered orally as cotreatment. Animals were treated for 28 days and euthanized 1 h after the last drug administration. Evaluated body weight, serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, g-glutamyl transferase, total protein, albumin, hepatic malondialdehyde content, superoxide dismutase, catalase, cytochrome P450 2E1 (CYP2E1)activity and glutathione (GSH). Results: WT extract prevented isoniazid-induced hepatotoxicity, indicated by both diagnostic indicators of liver damage, liver functional profile, significantly inhibited CYP2E1 activity, markedly attenuated oxidative stress by improved enzymatic, non-enzymatic antioxidants levels and mitigate malondialdehyde, lipid hydroperoxide significantly. Conclusions: These results suggest that WT extract exerts its hepatoprotective activity by inhibiting the production of free radicals and acts as a scavenger, reducing the free radical generation via inhibition of hepatic CYP2E1 activity, increasing the removal of free radicals through the induction of antioxidant enzymes and improving non-enzymatic thiol antioxidant GSH.

약물대사효소 CYP2D6와 N-acetyltransferase 활성의 고령화에 따른 변화에 관한 연구

배균섭,장인진,임형석,이경훈,임동석,신상구 大韓臨床藥理學會 2002 臨床藥理學會誌 Vol.10 No.2

Alopecia as uncommon side-effect of anti-tuberculosis drugs

( Si Young Yang ),( Joon Ki Kim ),( Kang Su Kim ),( Ji Eun Hahm ),( Chul Woo Kim ),( Sang Seok Kim ) 대한피부과학회 2019 대한피부과학회 학술발표대회집 Vol.71 No.1

Alopecia is very common condition in clinical practice with various etiologies. Drugs are common causes of alopecia. Among them, anti-mitotic drugs frequently induce alopecia. However, alopecia due to anti-tuberculosis drugs has rarely been reported in literature. It has been reported with only isoniazid, thiacetazone and ethionamide. A 64-year-old woman presented with indurated erythematous patches on her right lower leg. Based on histological and laboratory examinations, the lesions were suspected as cutaneous tuberculosis infection. She was started on anti-tuberculosis therapy initially with isoniazid, ethambutol, rifampicin, pyrazinamide and vitamin B6. After 1 month of medication, the cutaneous lesion was gradually improved. However, she complained of alopecia after 3 months of medication that became worsening. On physical examination, there was no sign of inflammation or nutritional deficiencies. Skin biopsy revealed numerous eosinophils on periappendageal areas. Therefore, drug-induced alopecia was considered. Because the regimen didn’t include thioacetazone or ethionamide, the causative agent was considered as isoniazid. Since then, isoniazid was stopped. The hair regrowth was observed after 4 weeks with complete recovery after 8 weeks from the cessation of isoniazid.

이소니아지드와 리팜핀 복합 치료에 의하여 발생한속섬유막뒤다리의 양측성 병변

박민원,노진홍,임서준,김민옥,김영수,김도형,권오영 대한신경과학회 2018 대한신경과학회지 Vol.36 No.4

Transient isoniazid-induced brain lesions have rarely been reported. The lesions were in the dentate nucleus of cerebellum and thalamus. Meanwhile, the neurotoxicity of rifampin has not been reported evidently. We observed bilateral lesions in the internal capsule in a young woman after taking a combination of isoniazid and rifampin. She transiently suffered numbness in both hands, dysarthria, and left side motor weakness while taking the medication. Isoniazid may induce structural lesions in various brain areas including the internal capsule.