Antituberculosis medications
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Antituberculosis medications
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Antimetabolites: Sulfonamides and trimethoprim
Antituberculosis medications
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Protein synthesis inhibitors: Tetracyclines
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Antituberculosis medications
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Antituberculosis medications
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Ethambutol p. 193, 194
Transcript
Antituberculosis medications are agents used to treat tuberculosis, a disease caused by the bacteria Mycobacterium tuberculosis.
Mycobacteria are an interesting bunch, they’re slender, rod-shaped, and need oxygen to survive, in other words, they’re “strict aerobes.”
They’ve got an unusually waxy cell wall, which is mainly a result of the production of mycolic acid.
This waxy cell wall makes them incredibly hardy, and allows them to resist weak disinfectants and survive on dry surfaces for months at a time.
Antituberculosis medications act mainly by preventing the production of mycolic acid and the synthesis of this cell wall.
Although about two billion people worldwide are infected with tuberculosis, or simply ‘TB, the vast majority, about 90-95%, don’t develop symptoms. And this is because usually the immune system can contain it.
So Mycobacterium tuberculosis is usually transmitted via inhalation, which is how they gain entry into the lungs.
TB can avoid the mucus traps and make its way to the deep airways and alveoli where we have macrophages which eat up foreign cells, digest, and destroy them.
With TB, they recognize foreign proteins on their cell surface, and phagocytize them, or essentially package them into a space called a phagosome.
With most cases, the macrophage then fuses the phagosome with a lysosome, which has hydrolytic enzymes that can pretty much break down any biochemical molecule.
TB’s tricky though, and once inside the macrophage, they produce a protein that inhibits this fusion, which allows the mycobacterium to survive.
It doesn’t just survive, though, it proliferates, and creates a localized infection.
Three weeks after initial infection, cell-mediated immunity kicks in, and immune cells surround the site of TB infection, creating a granuloma.
The tissue inside the middle dies as a result, a process referred to as caseous necrosis. This area is known as a “Ghon focus”.
In some cases, the mycobacteria is killed off by the immune system, and that’s the end of that.
Summary
Anti-tuberculosis (TB) medications are drugs used to treat tuberculosis. Common TB medications include Isoniazid (INH), Rifampin (RIF) Pyrazinamide (PZA), and Ethambutol (EMB). Other TB drugs include Streptomycin, Capreomycin, Amikacin, and Levofloxacin. TB drugs are typically administered in combination, which helps minimize resistance to one of the drugs.
Side effects of TB drugs include vitamin B6 deficiency for isoniazid. This is prevented by taking isoniazid with vitamin B6 supplements (pyridoxine). Other side effects include hepatotoxicity for isoniazid, ethambutol, and pyrazinamide; and thrombocytopenia and neutropenia for Rifampin.
Sources
- "Katzung & Trevor's Pharmacology Examination and Board Review,12th Edition" McGraw-Hill Education / Medical (2018)
- "Rang and Dale's Pharmacology" Elsevier (2019)
- "Goodman and Gilman's The Pharmacological Basis of Therapeutics, 13th Edition" McGraw-Hill Education / Medical (2017)
- "Treatment of Latent Tuberculosis Infection" Annals of Internal Medicine (2017)
- "Multidrug-Resistant Tuberculosis and Extensively Drug-Resistant Tuberculosis" Cold Spring Harbor Perspectives in Medicine (2015)
- "Molecular mechanism of the synergistic activity of ethambutol and isoniazid against Mycobacterium tuberculosis" Journal of Biological Chemistry (2018)
- "WHO consolidated guidelines on tuberculosis. Module 4" World Health Organization (2020)
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