Anti-Tuberculosis Drugs and Mechanisms of Action: Review

Abstract

Tuberculosis is the most important communicable disease in the world caused by the bacillus Mycobacterium tuberculosis. Mycobacterium is intrinsically resistant to most antibiotics and grows more slowly than other bacteria. Antibiotics are only active against rapidly growing bacterial cells. The cell wall of M. tuberculosis made up of lipid-rich polysaccharides, which are impermeable to many antibacterial agents as a result of poor penetration of drugs they develop resistance with increased level of antibiotic efflux and become Multiple Drug Resistance (MDRs). Prevention and quality diagnosis and treatment of MDR- and XDR-TB are part of the crucial interventions included in the new World Health Organization (WHO) End TB Strategy, which is focused on the goal of TB elimination program. Combinations of two or more drugs are used to overcome the obstacles to prevent emergence of resistance during the course of treatment. Based on drugs used for mycobacterial infections, treatment is administered for months to years. Anti-tuberculosis drugs are classified based on clinical response as first-line drugs and second-line drugs. First Line drugs with high anti-tubercular efficacy as well as low toxicity – routinely used Isoniazid (H), Rifampin (R), Pyrazinamide (Z), Isoniazid (H), Rifampin (R), Pyrazinamide (Z), Ethambutol (E), Streptomycin (S) – HRZES. Second Line drugs are with low anti-tubercular efficacy or high toxicity Paraminosalicylic Acid, Cycloserine, Kanamycin, Amikacin, Ciprofloxacin, Olfloxacin, Clarithromycin, and Azithromycin. Modes of action of majority of the anti-mycobacterial drugs either inhibit their cell wall synthesis or their protein synthesis. In spite of the limitations, the evidence accumulated in the last few years suggests that a new classification of the anti-TB drugs is necessary in the near future.