use of isoniazid in treating tb

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The problem:
Tuberculosis has been known to mankind since ancient times. Earlier this disease has been called by numerous names including ‘consumption’ (because of the severe weight loss) and ‘the white plague.’ Mycobacterium tuberculosis (the bacteria that causes TB), existed 15,000 to 20,000 years ago. In the 18th century in Western Europe, tuberculosis reached its peak with a occurrence as high as 900 deaths per 100,000.2

What is tuberculosis (TB disease)?
Tuberculosis is a contagious airborne disease that affects the lungs of humans and some animals i.e. cattle. If tuberculosis is left untreated and allowed to spread, it can then also affect the brain, kidneys, spine or other organ systems. As tuberculosis strikes the lungs a hole can develop which can cause an accumulation of air or fluid between the chest wall and lungs. This causes one of many tuberculosis symptoms: chest pain, and shortness of breath. (See fig.2) Infections can erode a blood vessel and the patient can bleed to death, or they can slowly suffocate as lungs become filled with tubercles.4

Cause of tuberculosis:
Tuberculosis can be caused by one of the four different organisms belonging to the genus mycobacterium: Mycobacterium bovis, Mycobacterium africanum, Mycobacterium microti and Mycobacterium tuberculosis. However, the leading cause of tuberculosis in humans is due to Mycobacterium tuberculosis, 9 which was discovered in 1882 by the German physician Robert Koch.10
Mycobacterium is a bacillus –a rod shaped, cord forming, bacteria. The reason the organism creates problems for its host is due to the fact that its cell wall contains large wax like lipids called mycolic acids. Mycolic acids are strong hydrophobic molecules that form a lipid...

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...otic inhibits the β-subunit of the RNA polymerase. This is an enzyme that transcribes bacterial RNA. Rifampicin does this by binding to RNA polymerase and blocking RNA synthesis, by physically preventing extension of RNA products.27

Pyrazinamide: The enzyme pyrazinamidase, in Mycobacteria, converts pyrazinamide to the active form pyrazinoic acid. Under acidic conditions, the pyrazinoic acid slowly leaks out and is thought to diffuse into the bacilli and gather, preventing mycolic acid synthesis.29

Ethambutol: Obstructs the formation of the cell wall. Mycolic acids attach to the 5'-hydroxyl forming a mycolyl-arabinogalactan-peptidoglycan complex in the cell wall. This inhibits the enzyme arabinosyl transferase. Disruption of the arabinogalactan synthesis, inhibits the formation of this complex and leads to increased permeability of the cell wall.30

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