ANTITUBERCULAR AGENTS (antituberculous agents) are used to treat tuberculosis (TB), which is a disease caused by Mycobacter tuberculosis. In the past, tuberculosis was a major killer, but mortality rates in developing countries showed a steady decline with increasing affluence, and there were dramatic falls in the rates in the 20th Century with the introduction of the BCG vaccination, which was then followed with the development of effective chemotherapy for treat tuberculosis. However, the incidence of treat tuberculosis is now rising and WHO regards treatment as a ‘global emergency’. The problem, identified several decades ago, is that of drug resistance. Traditionally, three drugs were combined, usually including isoniazid and streptomycin. The main drugs currently used include ethambutol, isoniazid, pyrazinamide and rifampicin, with capreomycin, cycloserine and streptomycin held in reserve. Compound therapy normally involved a first phase using isoniazid, rifampicin, pyrazinamide (and ethambutol if the organism is thought to be resistant). This is followed after two months by a second phase where two drugs are used, usually isoniazid and rifampicin. This is normally successful so long as patients continue the therapy until the disease is truly in remission. Isoniazid is a bacteriostatic antibacterial that is effective only against Mycobacteria. Its mechanism of action is not clear, though it is thought to inhibit bacterial cell wall synthesis. Cross-resistance with other antitubercular drugs does not occur. Rifampicin is an antibacterial and ANTIBIOTIC which is also used in leprosy. Chemically, it is an unusual antibiotic with a complex macrocyclic structure that works by inhibiting DNA-dependant RNA polymerase in prokaryotic, but not eukaryotic, cells. Ethambutol is active only against Mycobacteria. It is rapidly taken up by bacteria and immediately affects their growth. Resistance develops rapidly if the drug is used on its own. Pyrazinamide is active against the tubercular bacillus only at acid pH, and consequently is active against intracellular organisms in macrophages. Resistance develops readily, but it does not show cross-resistance to isoniazid. Capreomycin is an injected peptide antibiotic that shows some cross-resistance with the aminoglycoside antibiotic kanamycin. Cycloserine is a broad-spectrum antibiotic that inhibits many bacteria by interfering with cell wall synthesis. Its use is limited to tuberculosis resistant to other drugs.