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ORGANIZATION OF CLASS

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The mycobacteria that cause tuberculosis and leprosy are very slow growing, so therapy must be continued for relatively long periods of time. To prevent the emergence of resistant strains, it is vital to employ combination therapy with as many as four or five agents to which the organism is sensitive. The current treatment regimen for TB (which is subject to change) is 2 months of isoniazid, rifampin, pyrazinamide, and ethambutol, followed by 4 months of isoniazid and rifampin. Increasing the duration of therapy or changing the choice of drugs depends on culture and sensitivity results and factors that increase risk of treatment failure.

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The drugs for TB are most commonly divided into two groups: first-line drugs and second-line drugs. For most purposes, knowledge of the first-line drugs is adequate. If you decide to specialize in infectious disease or the treatment of tuberculosis, then a working knowledge of the other drugs is important.

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First-Line Drugs Second-Line Drugs
ISONIAZID amikacin
PYRAZINAMIDE aminosalicylic acid
RIFAMPIN capreomycin
ETHAMBUTOL cycloserine
ethionamide
kanamycin
levofloxacin
moxifloxacin
rifabutin
rifapentine
streptomycin

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Streptomycin was covered in more detail in Chapter 27, so we won’t consider it again.

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ISONIAZID

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ISONIAZID inhibits synthesis of mycolic acids.

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Isoniazid has a very simple structure. It works on mycobacteria by inhibiting the synthesis of mycolic acids that are unique to the mycobacteria. The mycolic acids are constituents of the bacterial cell envelope.

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There are patients who are fast and slow acetylators of ISONIAZID.

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You may have already heard mention of fast and slow acetylators. This is a genetically determined trait. Acetylation is a metabolic pathway for many drugs, but this pathway is of particular importance for isoniazid. Isoniazid has a shorter half-life in fast acetylators.

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ISONIAZID is associated with hepatotoxicity and peripheral neuropathy.

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Hepatitis is the most severe side effect of isoniazid. Isoniazid-induced liver dysfunction (as measured by liver function tests) can occur in 10% to 20% of patients, and the incidence increases with age. The liver dysfunction is reversible in most patients.

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The peripheral neuropathy results from pyridoxine deficiency. This deficiency results from a chemical combination of isoniazid and pyridoxine. It can be corrected by pyridoxine supplementation.

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ISONIAZID is the drug of choice for chemoprophylaxis in recent converters.

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If a person has had negative TB tests (purified protein derivative [PPD] test) in the past, and then 1 year later the test is positive, that person is said to be a recent converter. The current recommendations (of course, subject to change) is that the person be placed on isoniazid for 9 months, as long as there is no evidence of clinical disease, such as a positive chest x-ray.

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RIFAMPIN

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