Antituberculosis Drugs

Capreomycin and viomycin show activity against M. tuberculosis and may be regarded as being second-line antituberculosis drugs. 

Vannelli TA, A Dykman, PR Ortiz de Montellano (2002) The antituberculosis drug ethionamide is activated by a flavin monooxygenase. J Biol Chem 277 12824-12829. 

TABLE 72-4. Antituberculosis Drugs for Adults and Children332 (Continued)... 

N,A -bis(2-phyidylmethyl)pyrazine-2,3-dicarboxamide was crystallized in two orthorhombic forms, which differ from each other in the conformational arrangements of the compound [44], A new polymorph of 2-bromo-5-hydroxybenzaldehyde has been reported where a pair of hydrogen bonds linked molecules related by a center of inversion [45], One of the intermediates important in the synthesis of an antituberculosis drug, methyl p-aminobenzoate, was found to crystallize in a new monoclinic polymorph where molecules were arranged in head-to-tail linear ribbon arrays [46]. 

Tuberculosis remains a major global public health problem. The World Health Organization estimates that there are 8 million new cases of tuberculosis and 3 million deaths directly attributable to tuberculosis each year [22], Drug resistance is a serious problem worldwide. In a study in New York City, 33% of patients with tuberculosis were infected by organisms resistant to at least one antituberculosis drug, and 19% were infected by organisms resistant... 

Several reports are available on the biological activities of thioamide derivatives. The thioamide derivatives have shown significant activities, such as antituberculosis drug, anti-influenza virus activity, antitumor activity, anthelmintic activity, opioid receptor binding property, etc.94 101... 

Table 49-4 lists options for treatment of culture-positive pulmonary TB caused by drug-susceptible organisms. Doses of antituberculosis drugs are given in Table 49-5. The standard TB treatment regimen INH, RIF, pyrazinamide, and ethambutol for 2 months followed by INH and RIF for 4 months. 

In all Mycobacterium spp. two conserved PPTases are found an AcpS that activates two FASs and another PPTase that acts on NRPSs and PKSs that are involved in the biosynthesis of virulence factors. The essential role of both PPTases was demonstrated for the survival of Mycobacterium smegmatis, making them promising targets for the development of new antituberculosis drugs. 

Espinal MA, Laszlo A, Simonsen L, et al. Global trends in resistance to antituberculosis drugs. N Engl J Med 2001 344 1294-303. 

It is used to treat sepsis, meningitis, osteomyelitis, peritonitis, pneumonia, pyelonephritis, pyelocystitis, infected wounds, and post-operational, purulent complications that are caused by microorganisms sensitive to this drug. Kanamycin is used to treat tuberculosis of the lungs and other organs upon resistance to other antituberculosis drugs. Synonyms of this drug are karmycin, kamaxin, resistomycin, and many others. 

Multidrug resistance The most recent cultures should undergo susceptibility testing to all antituberculosis drugs if cultures remain positive after 3 to 4 months of treatment. 

Pulmonary tuberculosis Use in conjunction with at least 1 other antituberculosis drug(s). 

Retreatment In patients who have received previous antituberculosis therapy, administer 25 mg/kg (11 mg/lb) as a single oral dose once every 24 hours. Concurrently administer at least 1 other antituberculosis drug(s) to which the organisms have been demonstrated to be susceptible by in vitro tests. Suitable drugs usually include those not previously used in the treatment of the patient. After 60 days of administration, decrease the dose to 15 mg/kg and administer as a single oral dose once every 24 hours. 

Administer pyrazinamide with other effective antituberculosis drugs. It is administered for the initial 2 months of a 6-month or longer treatment regimen for drug... 

Hypersensitivity reactions Has occurred when capreomycin and other antituberculosis drugs were given concomitantly. 

Tuberculosis For the treatment of pulmonary tuberculosis (TB). Rifapentine must always be used in conjunction with at least 1 other antituberculosis drug(s) to which the isolate is susceptible. 

Aziz MA, Wright A, Laszlo A, De Muynck A, Por-taels F, Van Deun A et al. Epidemiology of antituberculosis drug resistance (the Global Project on Antituberculosis Drug Resistance Surveillance) an updated analysis. Lancet 2006 368(9553) 2142-54. 

Pyrrolopyridinone 32 has been proposed as a possible precursor of simplified analogues of the isoniazid-NAD adduct, 33. The compound may have potential use as an antituberculosis drug <20050BC666>. 

Problem 20.32 From picolines prepare (a) the vitamin niacin (3-pyridinecarboxylic acid), (b) the antituberculosis drug isoniazide (4-pyridinecarboxylic acid hydrazide). 

The effectiveness of progestin-only pills is reduced by hepatic enz5me-inducing drugs such as the anticonvulsants, phenytoin, carbamazepine barbiturates the antituberculosis drug rifampin protease inhibitors and herbal preparations containing St. John s wort (H. perforatum)... 

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