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Respiratory Infections
Published in Miriam Orcutt, Clare Shortall, Sarah Walpole, Aula Abbara, Sylvia Garry, Rita Issa, Alimuddin Zumla, Ibrahim Abubakar, Handbook of Refugee Health, 2021
Duration of TB treatment depends on the site of TB (6 months for pulmonary, lymphadenitis and gastrointestinal TB; 9 months for spinal TB; 12 months for CNS TB; and >18 months for drug-resistant TB, although 9-month MDR-TB regimens are available for specific cases (see ‘Bangladesh’ regimen).4 Adjunctive steroids should be used in CNS TB. The intensive phase consists of four drugs – rifampicin, isoniazid, pyrazinamide and ethambutol – and the continuation phase involves two drugs, usually rifampicin and isoniazid. If pyrazinamide is not used in the intensive phase (e.g. due to hepatotoxicity or side effects), the continuation phase is increased to 7 months (total treatment 9 months). An all oral 18–20-month treatment regimen for MDR-TB is now recommended by WHO for particular cases5 (reference: Frequently asked questions on the WHO Rapid Communication: key changes to the treatment of multidrug- and rifampicin – resistant TB. https://www.who.int/tb/publications/2018/MDR_RR-TB-TaskForce-FAQs-Updated-June2019.pdf). Recently, a new TB drug, pretomanid, has received approval in the United States of America (USA) in a combination regimen with bedaquiline and linezolid for people with XDR-TB or treatment-intolerant/non-responsive MDR-TB.
Tuberculosis in Childhood and Pregnancy
Published in Lloyd N. Friedman, Martin Dedicoat, Peter D. O. Davies, Clinical Tuberculosis, 2020
Lindsay H. Cameron, Jeffrey R. Starke
The rates of adverse reactions to antituberculosis medications are low enough in children and adolescents that routine baseline and monitoring of hepatic function tests is not necessary. If there is a previous history of hepatitis, obesity (fatty liver) or other chronic illness, it is advisable to obtain a baseline hepatic function panel. If the patient or family reports any symptoms that could be adverse reactions to antituberculosis medications, the child should have a complete physical examination and a hepatic function panel (including bilirubin level determination). Serum liver enzyme elevations of 2 times normal are fairly common and do not necessitate discontinuation of medications if all other findings are normal. Pyrazinamide may cause mild arthralgia or arthritis that is usually transient. Rash and severe pruritus are less common in children. Children receiving ethionamide should have baseline thyroid function testing and monitoring every 6 months to evaluate for hypothyroidism. Rifapentine can cause muscle aches that are generally self-limited and require no intervention. Adverse reactions with fluoroquinolones are uncommon.
Infectious Diseases
Published in Stephan Strobel, Lewis Spitz, Stephen D. Marks, Great Ormond Street Handbook of Paediatrics, 2019
Vas Novelli, Delane Shingadia, Huda Al-Ansari
INH 10 mg/kg/day and rifampicin 10–15 mg/kg/day are given for a total of 1 year. Pyrazinamide 30 mg/kg/day and ethambutol 15 mg/kg/day (streptomycin may be given instead) are also given for the first 2 months. There is some evidence that steroids are beneficial and these should be administered for the first 4–6 weeks. Early surgical intervention, in the form of placement of a ventriculoperitoneal (V-P) shunt or external ventricular drain, may be required for management of hydrocephalus and severe disease.
Evidence of drug-induced hepatotoxicity in the Maghrebian population
Published in Drug and Chemical Toxicology, 2022
Mohammed Bourhia, Riaz Ullah, Ali S. Alqahtani, Samir Ibenmoussa
In the current research, it was reported that anti-tuberculosis drugs were the most incriminated therapeutic class involved in liver damage with the following percentages; Ethambutol 10%, isoniazid 16.3%, rifampicin 14.3%, and pyrazinamide 14.2%. These drugs were frequently used for the treatment of tuberculosis due to its broader spectrum of effects versus mycobacterial species and therefore were higher in induced liver damage (National Institutes of Health 2017). These findings were in agreement with the earlier reported data which showed that antibacillaries induced hepatotoxicity with 7.4% of total affected patients with drug-induced hepatotoxicity (Nadir et al.2001). These findings were also in accordance with the previous literature which reported that pyrazinamide, isoniazid, and rifampicin are known for their hepatotoxicity effects (Tittarelli et al.2017).
Synthesis of novel, DNA binding heterocyclic dehydroabietylamine derivatives as potential antiproliferative and apoptosis-inducing agents
Published in Drug Delivery, 2020
Fengyi Zhao, Xu Sun, Wen Lu, Li Xu, Jiuzhou Shi, Shilong Yang, Mengyi Zhou, Fan Su, Feng Lin, Fuliang Cao
Recently, nitrogen heterocycles have also been reported to exhibit therapeutics anticancer (Azuine et al., 2004; Lei et al., 2019a,c) and anti-microbial (Nomiya et al., 2000; Mathew et al., 2006) activities. Among them, the pyrazine heterocycles have widespread application in food science, materials, and medicinal chemistry (Mondal et al., 2010; Saito et al., 2010; Badrinarayanan & Sperry, 2011; Zitko et al., 2011). For example, pyrazinamide, a pyrazine derivative, is an antimicrobial agent that is most commonly used for treatment of active tuberculosis during the initial phase of therapy in combination with other agents. Quinoxaline compounds have been reported to possess a wide range of interesting biological properties such as anticancer, antiviral, antimicrobial, antifungal, antitubercular, anti-inflammatory, and anti-angiogenesis agents (Seitz et al., 2002; Smits et al., 2008; Vicente et al., 2009; Lee et al., 2010; Sridevi et al., 2010; Ingle et al., 2013; Aissi et al., 2014; Soozani et al., 2018), containing pyrazine motif. Ahmed et al. (2018) have synthesized several compounds and evaluated anticancer effects against three cancer lines (HCT-116, MCF-7, and HepG2), and the results revealed that pyrazine derivatives were the most active compounds with IC50 value of 1.89 and 2.05 Μm. Another pyrazine derivative, pyrazin-2(1H)-one, has attracted considerable attention due to its biological activities, such as anti-viral, antibacterial, anti-inflammatory, and anticancer (colon cancer therapies) activities (Lindsley et al., 2005).
Berberis aristata Ameliorates Testicular Toxicity Induced by Combination of First-Line Tuberculosis Drugs (Rifampicin + Isoniazid + Pyrazinamide) in Normal Wistar Rats
Published in Journal of Dietary Supplements, 2019
Radhika Sharma, Neha Goyal, Mandakini Singla, Vijay Lakshmi Sharma
As a result of cellular metabolism, reactive oxygen species (ROS) are produced in the body; at low concentration, they do not cause any harm, but at higher concentration they can cause adverse modifications to the cells and their components such as DNA, lipids, and proteins. Increase in production of ROS is a primary factor responsible for testicular toxicity. In our body, isoniazid is metabolized as isoniazid hydrazide or acetyl isoniazid by action of enzyme n-acetyl transferase (NAT-2) that further gets converted into hydrazine, which is a harmful metabolite leading to formation of free radicals (Ebrahimzadeh et al., 2009). Rifampicin in combination with isoniazid catalyzes the hydrolysis of isoniazid with the help of enzyme isoniazid hydrolase. Pyrazinamide metabolizes into 5-hydroxy pyrazinoic acid; the mechanism of action of pyrazinamide is not known, but it is thought to enhance the toxicity.