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TB Drugs - Coggle Diagram

- - - - resistance
        
        Mutations in the rpoB gene that encodes the ß subunit of RNA
      - Mechanism of action
        
        Inhibits RNA polymerase (RNAP), preventing mycobacterial RNA synthesis
    - - Mech
        
        bactericidal prodrug activated by the mycobacterial catalase-peroxidase KatG. The active form of the drug inhibits mycobacterial production of cell wall mycolic acids
      - inhibits hepatic CYP450.
      - for patients predisposed to neuropathy, supplemental pyridoxine is provided during INH therapy (reacts w/ B6 during metabolism & product is excreted)
  - - - Mech
        
        decreases macrophage intracellular pH to slow the growth of M. tuberculosis.
        
        inhibits the fatty acid synthetase I enzyme of M. tuberculosis to impede production of mycolic acid (TB cell wall)
        
        Inhibits bacterial translation & stops the rescue of blocked ribosomes by inhibiting interaction between RpsA & trans-translational pathway
        
        Inhibits aspartate decarboxylase, preventing the conversion of β-alanine to l-aspartate and thus hurting the downstream of CoA. CoA is an important cofactor in metabolism of fats, carbs, & protiens
      - resistance
        
        r mechanism of resistance to PZA arises from mutations in the pncA gene encoding PZase. Ribosomal protein S1 gene (rpsA) and asparate decarboxylase gene (panD) mutations are also associated with PZA resistance
  - - - inhibits mycobacterial arabinosyl transferases for bacterial cell wall
    - - Mutations in the embB gene can result in excessive production of arabinosyl transferase
- - - - Mech
        
        Delamanid → activated by Ddn (within F420 system) → forms reactive metabolites → block mycolic acid synthesis + generate nitrous oxide → cell wall destruction → bacterial death.