Pharmacological Basis of treatment

Tuberculosis treatment and its different regimens have scientific backgrounds for their formulations. To understand this, we need to know about the mode of action of each anti-TB drug first.

Mode of Action of Anti-TB Drugs

Anti-TB drugs have the following three actions:

1. Early bactericidal activity: Killing of actively growing bacilli (in the phase of rapid multiplication and uninhibited metabolic activity).
2. Sterilizing activity of persisting bacilli, i.e., metabolically inhibited organisms in a quasi-dormant state.
3. Ability to prevent the emergence of drug resistance.

The ranking of first-line drugs with respect to their type of activity is indicated in Table 1 below.

Table 1: Ranking of first-line anti-TB drugs used in the treatment of drug-sensitive TB, based on the mode of action and activity

Thus, each drug has unique characteristics and drug combinations will make the regimen more effective.

Need for Long Duration of Treatment of TB

• Anti-TB drugs mostly kill actively multiplying tubercle bacilli.
• When bacilli have low metabolic activity, i.e., when bacterial growth has almost come to a standstill and the organisms are “dormant”, they are not killed by otherwise bactericidal drugs. Such organisms are referred to as persisters*.
• Though they may survive in the presence of drugs, behaving as if they were drug-resistant, they are in fact susceptible to the drugs.
• Thus, if for some reason these organisms regain their ability to multiply freely, they would be killed by the very drugs that had not harmed them before.
• When dormant bacilli again become metabolically active and start multiplying during effective chemotherapy, they are soon killed.
• Once chemotherapy has been completed, the revived bacilli may continue to multiply and thus cause relapse.
• This explains why conventional chemotherapy needs to be of long duration.

Resources

• Training Modules (1-4) for Programme Managers and Medical Officers, 2020.
• Tuberculosis Case-finding and Chemotherapy: Questions and Answers, K. Toman.

 Assessment