Antituberculosis drugs first line

Recommended for any form of active tuberculosis when treatment with first-line drugs (isoniazid, rifampin) has failed. Use only with other effective antituberculosis... 

Antituberculosis drugs are classified as first-line and second-line. 

As a rule, a regimen of two, three, or four of the five first-line antituberculosis drugs (isoniazid, rifampicin, pyrazinamide, ethambutol, and streptomycin) is used in tuberculosis (1). The 6-month short-course regimen consists of isoniazid, rifampicin, and pyrazinamide for 2 months, followed by isoniazid and rifampicin for 4 months (1). It may be advisable to include ethambutol in the initial phase when isoniazid resistance is suspected or if the prevalence of primary resistance to isoniazid is over 4% in new cases. A 9-month regimen consisting of isoniazid and rifampicin is also highly successful (1). Treatment should always include at least two drugs to which the mycobacteria are susceptible. 

Multidrug-resistant tuberculosis generally results from inadequate therapy or lack of compliance with therapy. A strain of mycobacteria is called resistant when it is insensitive to one of the first-line drugs. It is called multiresistant when it is insensitive to both isoniazid and rifampicin. In this case other antituberculosis drugs may also be ineffective (35). In practice, at least two second-line antituberculosis drugs, selected on the basis of individual drug susceptibility, are given in combination with a fluoroquinolone (36). 

Capreomycin has been abandoned for the treatment of tuberculosis and replaced by first-choice drugs. In rare cases, it has been administered in infections with non-tuberculous mycobacteria when there is multiple drug resistance to the first-line antituberculosis drugs (1). 

Pyrazinamide (PZA) is an important first-line antituberculosis drug and was discovered in 1940. It is used as a main dmg in the treatment of MDR TB (Singh et al., 2006). PZA reduces the TB treatment from 12 months down to 6 months and it is absorbed orally with a dosage of 80 mg/kg body weight (Wade, 2004). It is a derivative of nicotinic acid (Konno et al., 1967 Loeffler et al., 2012) (Figure 11.2). 

Isoniazid (INH) is one of the most effective first-line oral antituberculosis drugs and it was introduced to the treatment since its introduction in 1952 (Bernstein et al., 1952). It is usually consumed orally with a dosage of 5 mg/kg body weight (Hmama, 2013) (Figure 11.3). 

An improved synthesis of mefloquine has been advanced [149]. Also the asymmetric total synthesis of the (+)-enantiomer of mefloquine hydrochloride has been described [150]. Modifications of mefloquine aimed at development of novel biologically active compounds, including antituberculosis drugs, have extensively been performed (Scheme 92) [ 151 ]. Compounds 215,216 were more active than mefloquine against M. tuberculosis (MIC 11.9-33 pM), some of derivatives have a better tuberculostatic activity than the first line tnbercnlostatic agent ethambutol (MIC = 15.9) [151]. 

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