Current Overview of Anti-Tuberculosis Drugs: Metabolism and Toxicities

Sarkar, Susmita; Ganguly, Advaita

doi:10.4172/2161-1068.1000209

Cited by 38 publications

(44 citation statements)

References 27 publications

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“…Further evidence supporting this is that EMB is an excellent chelating agent, which is able to form stable complexes with essential trace metals such as copper, zinc, and iron, and hence it is proposed that EMB administration could affect the normal functioning of various metal requiring enzymes, such as ADH, for example (Sarkar et al, 2016). The effect of EMB on ADH will consequently also influence the metabolism of other alcohols, including ethanol, which is discussed in more detail in the following section.…”

Section: Discussionmentioning

confidence: 99%

Time-Dependent Changes in Urinary Metabolome Before and After Intensive Phase Tuberculosis Therapy: A Pharmacometabolomics Study

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Preez

Ronacher

et al. 2019

OMICS: A Journal of Integrative Biology

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Pharmacometabolomics is a rapidly emerging omics science signaling the convergence of clinical pharmacology, metabolomics, precision medicine, and biomarker research. Tuberculosis (TB) treatment outcomes have complex biological, environmental, and social determinants and thus, represent a promising application of pharmacometabolomics. In samples of 23 patients undergoing intensive phase TB therapy for 4 weeks, we identified drug-induced host-metabolome variations before and at repeated time intervals post-treatment: (1) an overall reduction in the oxidative stress levels over the course of TB treatment; (2) a time-dependent induction and inhibition of several enzymes in response to the drugs (CYP2E1, CYP3A4, alcohol dehydrogenase, and aminocarboxymuconate-semialdehyde decarboxylase), and altered oxidative stress levels (aconitase, formylglycinegenerating enzyme, a-ketoglutarate dehydrogenase, and succinate-semialdehyde dehydrogenase); (3) an upregulated urea cycle; and (4) altered insulin production. This is the first study of its kind to indicate changes to the host metabolome in response to intensive TB treatment, at different time intervals during the course of treatment. These results provide new insights into the mechanisms of TB drug metabolism, drug action, and drugrelated side effects, thereby paving the way for the development of improved therapeutic approaches for the disease, and perhaps more importantly, also for monitoring treatment progression.

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Section: Discussionmentioning

confidence: 99%

Time-Dependent Changes in Urinary Metabolome Before and After Intensive Phase Tuberculosis Therapy: A Pharmacometabolomics Study

Combrink

Preez

Ronacher

et al. 2019

OMICS: A Journal of Integrative Biology

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“…Paradoxical TB-IRIS is a worsening or progress of new tuberculosis disease in patients taking ATD after initiating HAART. [11][12][13][14] Paradoxical reactions mostly occur within 4-12 weeks of treatment initiation. 8 This case occured 12 weeks after taking HAART.…”

Section: Discussionmentioning

confidence: 99%

“…The "paradoxical IRIS" diagnosis requires a diagnosis of TB and an underlying reaction to ATD, along with at least one of four major or two of three minor clinical criteria and exclusion of alternative explanations (International Network for the Study of HIV-associated IRIS/INSHI). 8,14,[20][21][22] Definition case of paradoxical TB-IRIS for use in resource settings: 8 In this case the diagnosis of TB (fulfill WHO criteria) is made before starting HAART. He is treated by giving ATD (450 mg rifampicin; 400 mg isoniazid; 1000 mg pyrazinamide; 750 mg ethambutol; 25 mg pyridoxin); all of the regimens are given once a day orally.…”

Section: Discussionmentioning

confidence: 99%

<p>A Challenge in Diagnosis of Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome (TB-IRIS)</p>

Suryana¹

2020

HIV

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Tuberculosis immune reconstitution inflammatory syndrome (TB-IRIS) in HIVinfected patients is the sign and symptom of exacerbation, or radiological manifestation of Mycobacterium tuberculosis (Mtb) infection, can describe the improvement of the immune system after initiating highly active antiretroviral therapy (HAART). No approved or explicit symptomatic tests for TB-IRIS exist, the diagnosis depends on the clinical manifestations. Here we report a TB-IRIS case with diagnostic challenges.

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“…The explanation for this is uncertain, and could involve a degree of survivorship bias or increased tolerance of side effects, but may relate to the presence of pyrazinamide in all three regimens. Pyrazinamide is a drug with a well-recognised toxicity profile [ 11 ], while ethambutol (the other drug only present for the intensive phase) has few reported side effects [ 27 ]. Additionally, hepatotoxicity and arthralgia were among the most common events and these are frequently reported side effects of pyrazinamide [ 28 , 29 ].…”

Section: Discussionmentioning

confidence: 99%

Toxicity associated with tuberculosis chemotherapy in the REMoxTB study

Tweed

Crook

Amukoye³

et al. 2018

BMC Infect Dis

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BackgroundThe incidence and severity of tuberculosis chemotherapy toxicity is poorly characterised. We used data available from patients in the REMoxTB trial to provide an assessment of the risks associated with the standard regimen and two experimental regimens containing moxifloxacin.MethodsAll grade 3 & 4 adverse events (AEs) and their relationship to treatment for patients who had taken at least one dose of therapy in the REMoxTB clinical trial were recorded. Univariable logistic regression was used to test the relationship of baseline characteristics to the incidence of grade 3 & 4 AEs and significant characteristics (p < 0.10) were incorporated into a multivariable model. The timing of AEs during therapy was analysed in standard therapy and the experimental arms. Logistic regression was used to investigate the relationship between AEs (total and related-only) and microbiological cure on treatment.ResultsIn the standard therapy arm 57 (8.9%) of 639 patients experienced ≥1 related AEs with 80 of the total 113 related events (70.8%) occurring in the intensive phase of treatment. Both four-month experimental arms (“isoniazid arm” with moxifloxacin substituted for ethambutol & “ethambutol arm” with moxifloxacin substituted for isoniazid) had a lower total of related grade 3 & 4 AEs than standard therapy (63 & 65 vs 113 AEs). Female gender (adjOR 1.97, 95% CI 0.91–1.83) and HIV-positive status (adjOR 3.33, 95% CI 1.55–7.14) were significantly associated with experiencing ≥1 related AE (p < 0.05) on standard therapy. The most common adverse events on standard therapy related to hepatobiliary, musculoskeletal and metabolic disorders. Patients who experienced ≥1 related AE were more likely to fail treatment or relapse (adjOR 3.11, 95% CI 1.59–6.10, p < 0.001).ConclusionsMost AEs considered related to standard therapy occurred in the intensive phase of treatment with female patients and HIV-positive patients demonstrating a significantly higher risk of AEs during treatment. Almost a tenth of standard therapy patients had a significant side effect, whereas both experimental arms recorded a lower incidence of toxicity. That patients with one or more AE are more likely to fail treatment suggests that treatment outcomes could be improved by identifying such patients through targeted monitoring.

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Current Overview of Anti-Tuberculosis Drugs: Metabolism and Toxicities

Cited by 38 publications

References 27 publications

Time-Dependent Changes in Urinary Metabolome Before and After Intensive Phase Tuberculosis Therapy: A Pharmacometabolomics Study

Time-Dependent Changes in Urinary Metabolome Before and After Intensive Phase Tuberculosis Therapy: A Pharmacometabolomics Study

<p>A Challenge in Diagnosis of Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome (TB-IRIS)</p>

Toxicity associated with tuberculosis chemotherapy in the REMoxTB study

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