Role of Reactive Metabolites in Drug-Induced Hepatotoxicity

Srivastava, Abhishek; Maggs, James L.; Antoine, Daniel J.; Williams, Dominic P.; Smith, Dennis A.; Park, B. K.

doi:10.1007/978-3-642-00663-0_7

Cited by 132 publications

(120 citation statements)

References 179 publications

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“…The half-life of isoniazid is approximately 1 h (range: 0.5-1.6 h) in patients with the rapid acetylator phenotype and 2-5 h in those with the slow acetylator phenotype; in patients with liver disease or kidney failure, the half-life of isoniazid can be even longer. (16,18) …”

Section: Metabolization and Excretionmentioning

confidence: 99%

Drogas antituberculose: interações medicamentosas, efeitos adversos e utilização em situações especiais - parte 1: fármacos de primeira linha

et al. 2010

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The main objectives of tuberculosis therapy are to cure the patients and to minimize the possibility of transmission of the bacillus to healthy subjects. Adverse effects of antituberculosis drugs or drug interactions (among antituberculosis drugs or between antituberculosis drugs and other drugs) can make it necessary to modify or discontinue treatment. We briefly review the new guidelines for the pharmacological treatment of tuberculosis, introduced by the Brazilian National Ministry of Health in 2009, and describe the general mechanism of action, absorption, metabolization, and excretion of the first-line drugs used in the basic regimen. We describe adverse drug reactions and interactions (with other drugs, food, and antacids), as well as the most appropriate approach to special situations, such as pregnancy, breastfeeding, liver failure, and kidney failure. We also describe the mechanisms by which the interactions among the antituberculosis drugs used in the basic regimen can cause druginduced hepatitis, and we discuss the alternatives in this situation.Keywords: Tuberculosis; Drug interactions; Antibiotics, antitubercular; Pharmacologic actions; Drug toxicity; Drug-induced liver injury. ResumoOs objetivos principais do tratamento da tuberculose são curar o paciente e minimizar a possibilidade de transmissão do bacilo para indivíduos saudáveis. Reações adversas ou interações das drogas antituberculose entre si e com outros fármacos podem causar modificação ou descontinuação da terapêutica. Revisamos sucintamente o novo tratamento farmacológico da tuberculose introduzido pelo Ministério da Saúde do Brasil em 2009 e mostramos os mecanismos gerais de ação, absorção, metabolização e excreção dos medicamentos utilizados no esquema básico. Descrevemos as reações adversas e as interações (com medicamentos, alimentos e antiácidos) assim como a abordagem mais adequada para situações especiais, como gravidez, amamentação, insuficiência hepática e renal. Também descrevemos os mecanismos pelos quais as interações das drogas antituberculose do esquema básico podem causar hepatite medicamentosa e as possíveis alternativas nessa situação.Descritores: Tuberculose; Interações de medicamentos; Antibióticos antituberculose; Ações farmacológicas; Toxicidade de drogas; Doença hepática induzida por drogas.

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Section: Metabolization and Excretionmentioning

confidence: 99%

Drogas antituberculose: interações medicamentosas, efeitos adversos e utilização em situações especiais - parte 1: fármacos de primeira linha

et al. 2010

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“…N-Acetylcysteine (NAC) is the antidote for acetaminophen poisoning because of its ability to increase the available glutathione for conjugation with NAPQI (Tucker, 1998). On the other hand, in clinical and experimental studies, many compounds have been investigated for their ability to protect against paracetamol-induced hepatotoxicity, and those possessing some useful features such as antioxidant, anticytokine, and anti-inflammatory properties were of particular interest (Chun et al, 2009;Jaeschke et al, 2011;Srivastava et al, 2010). However, the need for new treatment protocols remains high.…”

Section: Introductionmentioning

confidence: 99%

Protective effect of Panax ginseng against N-acetyl-p-aminophenol-induced hepatotoxicity in rats

Uzkeser¹

2012

Afr. J. Pharm. Pharmacol.

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Panax ginseng (PG) has been commonly used as medicinal herb for the treatment of various diseases in Eastern Asia for thousands of years. This study was designed to investigate the protective effect of PG against paracetamol-(N-acetyl-p-aminophenol; APAP)-induced liver damage in rats. Thirty-two albino Wistar rats were divided into four groups: Group C (control); Group APAP (gavaged orally with APAP (APAP, 2 g/kg, single dose); Group PG 100 mg/kg + APAP or 200 mg/kg + APAP (these two groups were treated by gavaging with PG (100 or 200 mg/kg) for 30 days following a single dose of APAP). APAP treatment alone induced hepatotoxicity, evidenced by significant increases in malondialdehyde (MDA) level and serum activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and tumor necrosis factor-α (TNF-α). In addition, the level of GSH in the liver was significantly reduced, as were the activities of superoxide dismutase (SOD) and catalase (CAT). Liver histopathological examination showed that APAP administration induced centrilobular necrosis and infiltration of lymphocytes. However, these biochemical and histological changes were prevented by PG pretreatment. In conclusion, our results suggest that PG may be considered a protective medicinal herb against APAP-induced liver injury.

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“…However, other risk factors and patient characteristics such as genetic polymorphism also play an important role in the event of drug toxicity. 23 HIV infection itself has been shown to affect the drug metabolic pathway as it is associated with a glutathione (GSH) depleted state. Glutathione plays an important role in the conjugation and metabolism of drugs and hence, in HIV infection, this typical detoxification pathway is hampered.…”

Section: Discussionmentioning

confidence: 99%

Selecting patients who can be re-challenged with Nevirapine in case of skin rash with Efavirenz – A Study

Dutta

Modak

et al. 2017

Sri Lankan J Infec Dis

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Introduction and Objectives: A common adverse effect of Efavirenz (EFV) -a first line drug used in treatment of patients with HIV infections is skin rash. In case of EFV-induced skin rash, the usual practice is to switch to a Protease Inhibitor (PI), as another nonnucleoside reverse transcriptase inhibitor (NNRTI) might have cross-reactivity with a higher incidence of skin rash which is often severe. The aim of the study was therefore to determine whether with careful evaluation and stratification, using predefined criteria of patients who developed rash with EFV, it might be possible to find a subset of patients among whom Nevirapine (NVP) may be safely used, sparing PIs for second-line treatment.

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Role of Reactive Metabolites in Drug-Induced Hepatotoxicity

Cited by 132 publications

References 179 publications

Drogas antituberculose: interações medicamentosas, efeitos adversos e utilização em situações especiais - parte 1: fármacos de primeira linha

Drogas antituberculose: interações medicamentosas, efeitos adversos e utilização em situações especiais - parte 1: fármacos de primeira linha

Protective effect of Panax ginseng against N-acetyl-p-aminophenol-induced hepatotoxicity in rats

Selecting patients who can be re-challenged with Nevirapine in case of skin rash with Efavirenz – A Study

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