Antituberculous Drugs and Drugs for Leprosy

• What is the current global infection rate of tuberculosis?

  1/3 of the world population is currently infected
• What is the second commonest cause of death from infectious disease?

  Tuberculosis is the second commonest cause of death from infectious disease
• How many cases of tuberculosis were reported in 2008?

  There were 9 million cases reported in 2008
• How many deaths from tuberculosis occurred in 2008?

  1.8 million deaths occurred from tuberculosis in 2008
• Why is tuberculosis treatment considered difficult?

  Because of its slow growth, dormancy, and difficult penetration by drugs
• What characteristic of the tuberculosis bacterium contributes to its resistance to drugs?

  The bacterium has a 'waxy' lipid-rich impermeable cell wall
• How does tuberculosis survive inside the body after phagocytosis?

  It has the ability to survive inside macrophages
• What is caseation and fibrosis in the context of tuberculosis?

  It refers to the blockade of blood vessels supplying the necrotic area
• What is the standard therapy for tuberculosis?

  Standard therapy involves combinations of drugs
• How long is tuberculosis treatment typically administered?

  Treatment is administered for months to years
• What are the main differences between Gram-positive and Gram-negative bacterial cell walls?

  • Gram-positive bacteria:
  • Thick murein layer
  • Lipoteichoic acids in outer leaflet
  • Gram-negative bacteria:
  • Two lipid bilayers
  • Thinner murein layer
  • Lipopolysaccharide (LPS) in outer membrane
• What is the composition of the bacterial cell wall?

  The bacterial cell wall is made of peptidoglycan/murein
• What role do lipoteichoic acids play in Gram-positive bacteria?

  They intercalate through the cell wall to the outer surface and are involved in adherence and evasion of the host immune system
• How do hydrophilic molecules cross the outer membrane of Gram-negative bacteria?


  They cross through channels called porins
• What is the function of lipopolysaccharide (LPS) in Gram-negative bacteria?

  LPS protects bacteria from disruption by hydrophilic host molecules and is important in adherence to host cells
• What are the main components of the mycobacterial cell wall?

  • Arabinogalactan
  • Mycolic acids
  • Peptidoglycan
  • Unique lipids (mycolic acids, etc.)
• What are the first-line anti-TB drugs that are bactericidal?

  Isoniazid, Rifampicin, Pyrazinamide, and Streptomycin
• What are the first-line anti-TB drugs that are bacteriostatic?

  Ethambutol and Thiacetazone
• What are the second-line anti-TB drugs that are bactericidal?

  Amikacin, Kapreomycin, Kanamycin, and Fluoroquinolones
• What are the second-line anti-TB drugs that are bacteriostatic?

  Ethionamide, Cycloserine, and Clofazimine
• What is the principle of tuberculosis treatment?

  A single drug should never be used
• What is Isoniazid derived from?

  Isoniazid is an isonicotinic acid derivative
• How is Isoniazid activated in the body?

  It undergoes activation by MTB enzymes (catalase-peroxidase)
• What is the mechanism of action of Isoniazid?

  It inhibits mycolic acid synthesis by forming a covalent complex with inhA and KasA
• What is the main metabolism pathway of Isoniazid?

  Acetylation is the main metabolism pathway
• How does genetic polymorphism affect Isoniazid metabolism?

  Slow acetylators are at higher risk of developing neuritis
• What are the adverse effects of Isoniazid?

  Rash, increased liver function tests, and peripheral neuropathy
• What is the mechanism of action of Rifampicin?

  It binds to and inhibits DNA-dependent RNA polymerase in prokaryotic cells
• What is a significant side effect of Rifampicin?

  Hepatotoxicity is a main side effect
• What is the role of Rifabutine in tuberculosis treatment?

  It is a rifampicin derivative used in HIV/TB patients treated concurrently with protease inhibitors
• What is the mode of action of Ethambutol?

  It inhibits arabinosyl transferase, disrupting arabinogalactan synthesis
• What are the adverse effects of Ethambutol?

  Optic neuritis and red-green color blindness
• What is the suggested mode of action of Pyrazinamide?

  It converts to pyrazinoic acid, which decreases the pH and retards MTB growth
• What are the first-line and second-line anti-TB drugs?

  First-line anti-TB drugs:

  • Bactericidal: Isoniazid, Rifampicin, Pyrazinamide, Streptomycin
  • Bacteriostatic: Ethambutol, Thiacetazone

  
  

  Second-line anti-TB drugs:

  • Bactericidal: Amikacin, Kapreomycin, Kanamycin, Fluoroquinolones
  • Bacteriostatic: Ethionamide, Cycloserine, Clofazimine
• What are the mechanisms of action for Isoniazid and Rifampicin?

  Isoniazid:

  • Inhibits mycolic acid synthesis
  • Forms a covalent complex with inhA and KasA

  
  

  Rifampicin:

  • Binds to and inhibits DNA-dependent RNA polymerase
• What is a characteristic side effect of interior uveitis?

  Interior uveitis is a characteristic side effect.
• How does the half-life of Rifapentine compare to that of rifampicin and rifabutine?

  Rifapentine has a longer half-life than rifampicin and rifabutine.
• Why is Rifapentine preferred for once-weekly dosing?

  Because it has a longer half-life.
• What is the effect of Ethambutol on organisms other than MTB?

  Ethambutol has no effect on organisms other than MTB.
• What type of effect does Ethambutol exert against actively growing MTB?

  Ethambutol exerts a bacteriostatic effect against actively growing MTB.