Drogas antituberculose: interações medicamentosas, efeitos adversos e utilização em situações especiais - parte 2: fármacos de segunda linha

Arbex, Marcos Abdo; Varella, Marília de Castro Lima; Siqueira, Helio Ribeiro de; Mello, Fernando Augusto Fiúza de

doi:10.1590/s1806-37132010000500017

Cited by 114 publications

(34 citation statements)

References 39 publications

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“…In contrast, the absorption of ETH from the GI tract of the guinea pig appears to be slightly delayed (Tmax = 0.39 h), limited and variable. Despite limited reports of rapid and complete ETH absorption when administered to humans 36 , a larger number of studies describe the pattern of ETH absorption as “erratic” and that delayed absorption is typically common 23, 25, 37 . The Tmax in healthy volunteers is reported to be between 1.02 h and 2.6 h depending on the formulation (film or enteric coated tablet) and co-administration of food or antacids 23, 38–40 .…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of Ethionamide Delivered in Spray-Dried Microparticles to the Lungs of Guinea Pigs

García-Contreras

Padilla-Carlin

Sung

et al. 2017

Journal of Pharmaceutical Sciences

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The use of ethionamide (ETH) in treating multi-drug resistant tuberculosis is limited by severe side effects. ETH disposition after pulmonary administration in spray dried particles might minimize systemic exposure and side effects. Methods Spray dried ETH particles were optimized for performance in a dry powder aerosol generator (DPAG) and exposure chamber. ETH particles were administered by the IV, oral, or pulmonary routes to guinea pigs. ETH appearance in plasma, bronchoalveolar lavage and lung tissues were measured and subjected to non-compartmental pharmacokinetic analysis. Results DPAG dispersion of 20% ETH particles gave the highest dose at the exposure chamber ports and fine particle fraction of 72.3%. Pulmonary ETH was absorbed more rapidly and to a greater extent than orally administered drug. At Tmax, ETH concentrations were significantly higher in plasma than lungs from IV dosing, whereas, following insufflation lung concentrations were 5-fold higher than in plasma. AUC(0-t), and CL were similar after IV administration and insufflation. AUC(0-t) after oral administration was 6–7-fold smaller and CL was 6-fold faster. Notably, ETH bioavailability after pulmonary administration was significantly higher (85%) than after oral administration (17%). Conclusion Pulmonary ETH delivery would potentially enhance efficacy for TB treatment given the high lung concentrations and bioavailability

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of Ethionamide Delivered in Spray-Dried Microparticles to the Lungs of Guinea Pigs

García-Contreras

Padilla-Carlin

Sung

et al. 2017

Journal of Pharmaceutical Sciences

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“…Others studies have found high prevalences (more than 50%) of adverse drug reactions among MDR-TB patients [26], [27] compared to the expected prevalence of mild reactions in those using first-line therapy (around 5–20%) [19]. In general, drugs for treating MDR-TB strains have greater toxicity effects and involve a long-term exposure (18 to 24 months), all in great contrast with the treatment of a sensitive strain of TB [28].…”

Section: Discussionmentioning

confidence: 99%

Factors Associated with Anti-Tuberculosis Medication Adverse Effects: A Case-Control Study in Lima, Peru

et al. 2011

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BackgroundLong-term exposure to anti-tuberculosis medication increases risk of adverse drug reactions and toxicity. The objective of this investigation was to determine factors associated with anti-tuberculosis adverse drug reactions in Lima, Peru, with special emphasis on MDR-TB medication, HIV infection, diabetes, age and tobacco use.Methodology and ResultsA case-control study was performed using information from Peruvian TB Programme. A case was defined as having reported an anti-TB adverse drug reaction during 2005–2010 with appropriate notification on clinical records. Controls were defined as not having reported a side effect, receiving anti-TB therapy during the same time that the case had appeared. Crude, and age- and sex-adjusted models were calculated using odds ratios (OR) and 95% confidence intervals (95%CI). A multivariable model was created to look for independent factors associated with side effect from anti-TB therapy. A total of 720 patients (144 cases and 576 controls) were analyzed. In our multivariable model, age, especially those over 40 years (OR = 3.93; 95%CI: 1.65–9.35), overweight/obesity (OR = 2.13; 95%CI: 1.17–3.89), anemia (OR = 2.10; IC95%: 1.13–3.92), MDR-TB medication (OR = 11.1; 95%CI: 6.29–19.6), and smoking (OR = 2.00; 95%CI: 1.03–3.87) were independently associated with adverse drug reactions.ConclusionsOld age, anemia, MDR-TB medication, overweight/obesity status, and smoking history are independent risk factors associated with anti-tuberculosis adverse drug reactions. Patients with these risk factors should be monitored during the anti-TB therapy. A comprehensive clinical history and additional medical exams, including hematocrit and HIV-ELISA, might be useful to identify these patients.

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“…Reports have shown that there is alteration in thyroid hormone levels in patients with non-thyroid illnesses such as TB. This alteration has been attributed to anti-TB drugs especially, the secondline anti-TB drugs which cause more adverse effects than the first-line anti-TB drugs used for the treatment of drug-sensitive TB 9 . The exact mechanism responsible for the alteration is still unknown 8,10 , though the following mechanisms were suggested; viz: decreased T4 to T3 conversion, decreased TSH production and action of drugs such as ethionamide and prothionamide used for the treatment of MDR-TB on the thyroid causing hypothyroidism by inhibiting thyroid hormone synthesis through inhibition of iodine organification [11][12][13] .…”

Section: Management Of Mdr-tb Is Daunting Especially Whenmentioning

confidence: 99%

Thyroid function in multidrug-resistant tuberculosis patients with or without human immunodeficiency virus (HIV) infection before commencement of MDR-TB drug regimen

et al. 2016

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Background: Mycobacterium tuberculosis and human immunodeficiency virus (HIV) are known to cause abnormal thyroid function. There is little information on whether HIV infection aggravates alteration of thyroid function in patients with MDR-TB. Objectives: This study was carried out to determine if HIV co-infection alters serum levels of thyroid hormones (T3, T4) and thyroid stimulating hormone (TSH) in patients with MDR-TB patients and to find out the frequency of subclinical thyroid dysfunction before the commencement of MDR-TB therapy. Methods: This observational and cross-sectional study involved all the newly admitted patients in MDR-TB Referral Centre, University College Hospital, Ibadan, Nigeria between July 2010 and December 2014. Serum levels of thyroid stimulating hormone (TSH), free thyroxine (fT4) and free triiodothyronine (fT3) were determined using ELISA. Results: Enrolled were 115 patients with MDR-TB, out of which 22 (19.13%) had MDR-TB/HIV co-infection. Sick euthyroid syndrome (SES), subclinical hypothyroidism and subclinical hyperthyroidism were observed in 5 (4.35%), 9 (7.83%) and 2 (1.74%) patients respectively. The median level of TSH was insignificantly higher while the median levels of T3 and T4 were insignificantly lower in patients with MDR-TB/HIV co-infection compared with patients with MDRT-TB only. Conclusion: It could be concluded from this study that patients with MDR-TB/HIV co-infection have a similar thyroid function as patients having MDR-TB without HIV infection before commencement of MDR-TB drug regimen. Also, there is a possibility of subclinical thyroid dysfunction in patients with MDR-TB/HIV co-infection even, before the commencement of MDR-TB therapy.

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Drogas antituberculose: interações medicamentosas, efeitos adversos e utilização em situações especiais - parte 2: fármacos de segunda linha

Cited by 114 publications

References 39 publications

Pharmacokinetics of Ethionamide Delivered in Spray-Dried Microparticles to the Lungs of Guinea Pigs

Pharmacokinetics of Ethionamide Delivered in Spray-Dried Microparticles to the Lungs of Guinea Pigs

Factors Associated with Anti-Tuberculosis Medication Adverse Effects: A Case-Control Study in Lima, Peru

Thyroid function in multidrug-resistant tuberculosis patients with or without human immunodeficiency virus (HIV) infection before commencement of MDR-TB drug regimen

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