unit 13 drugs PBL

• RIPE - R


  Rifampicin

  TARGET: DNA dependent RNA polymerase

  ACTIVITY: Binds to the beta subunit of bacterial DNA-dependent RNA polymerase, a vital enzyme responsible for transcribing DNA into messenger RNA/ Results in reduced RNA synthesis
• RIPE - I


  Isoniazid – Prodrug (Given with pyridoxine)

  Target: InhA (Enoyl Reductase)

  InhA is an enoyl-acyl carrier protein reductase enzyme that is part of the fatty acid synthase II system in Mtb, critical for synthesis of mycolic acids

  Action: Inhibitor of InhA, blocking the synthesis of mycolic acids
• RIPE - P


  Pyrazinamide - Prodrug

  TARGET: Fatty acid synthesis (FAS-1)

  Action: Inhibits the fatty acid synthase I enzyme, which is involved in the synthesis of mycolic acids

  
  

  Converted into its active form, pyrazinoic acid, by the bacterial enzyme pyrazinamidase. This disrupts the membrane potential and interferes with the energy production of the mycobacterial cells.
• RIPE - E


  Ethambutol

  TARGET: L-Arabinosyltransferase

  Action: Inhibition of arabinosyltransferases, enzymes involved in the biosynthesis of arabinogalactan. Reduced arabinogalactan biosynthesis, leading to a weakening of the cell wall integrity
• Ethambutol


  Ethambutol diffuses into Mycobacterium cells. Once inside the cell, ethambutol inhibits the arabinosyltransferases (embA, embB, and embC), preventing formation of the cell wall components arabinogalactan and lipoarabinomannan, and preventing cell division.
• Rifampin works by binding to the beta-subunit of microbial DNA-dependent RNA polymerase (RNAP),6 thereby inhibiting the enzyme and impeding RNA synthesis. It reduces the affinity of RNAP for short RNA transcripts. 
• Isoniazid is a prodrug and must be activated by bacterial catalase. Once activated, isoniazid inhibits the synthesis of mycoloic acids, an essential component of the bacterial cell wall. At therapeutic levels isoniazid is bacteriocidal against actively growing intracellular and extracellular Mycobacterium tuberculosis organisms. Specifically isoniazid inhibits InhA, the enoyl reductase from Mycobacterium tuberculosis, by forming a covalent adduct with the NAD cofactor. It is the INH-NAD adduct that acts as a slow, tight-binding competitive inhibitor of InhA.
• tuberculosis cell walls contain fatty molecules known as mycolic acids, which make the bacteria less susceptible to antibiotics. These molecules also help the bacteria to subvert and then hide from the immune system.