Antimycobacterial Drugs

Question 1

Drugs for tuberculosis

Answer 1

• Isoniazid
• Rifampin
• Ethambutol
• Pyrazinamide
• Streptomycin

Question 2

Isoniazid (INH)

Answer 2

• Inhibit enzymes required for the synthesis of mycolic acids and mycobacterial cell walls.
• High-level resistance –> deletion of katG gene that codes for a catalase involved in the bioactivation of INH
• Low-level resistance –> deletions in inhA gene that codes for the “target”, an acyl carrier protein synthesis
• Single most important drug used in tuberculosis and is a component of most drug combination regimens.
• Given as the sole drug in prophylaxis (treatment of latent infection)

Question 3

Rifampin

Answer 3

• Bactericidal
• Inhibits DNA-dependent RNA polymerase (rpo gene) in M. tuberculosis and many other microorganisms
• Eliminated in feces - orange colored
• Always used in combination with other drugs against tuberculosis
• Used against latent tuberculosis in INH-intolerant patients
• Used in meningococcal and staphylococcal carrier state
• Cause proteinuria

Question 4

Ethambutol

Answer 4

• Inhibits arabinosyl transferase (embCAB operon) involved in synthesis of arabinogalactan, a component of mycobacterial cell walls
• Used mainly in tuberculosis, always in combination with other drugs
• Causes visual disturbances

Question 5

Pyrazinamide

Answer 5

• Bacteriostatic
• Not known mechanism, but its action requires metabolic conversion via pyrazinamidases (pncA gene) present in M. tuberculosis
• Used in “short-course” treatment regimens in combination with other antituberculous drugs

Question 6

Streptomycin

Answer 6

• Used principally in drug combinations for the treatment of life-threatening tuberculous disease, including meningitis, military dissemination, and severe organ tuberculosis

Question 7

Second-line tuberculous drugs

Answer 7

• Amikacin
• Ciprofloxacin
• Ofloxacin
• Ethionamide
• p-Aminosalicylic acid (PAS)

Question 8

Amikacin

Answer 8

• Treatment of tuberculosis caused by streptomycin-resistant or multi-drug-resistant mycobacterial strains
• Always used in combination regimens
• Cause loss of equilibrium and auditory damage

Question 9

Ciprofloxacin, Ofloxacin

Answer 9

• Active against M. tuberculosis strains that are resistant to first-line drugs.

Question 10

Drugs for leprosy

Answer 10

• Dapsone
• Acedapsone
• Clofzimine

Question 11

Dapsone

Answer 11

• Most active drugs against M. leprae

- Inhibit folic acid synthesis

Question 12

Acedapsone

Answer 12

• Provides inhibitory plasma concentrations for several months
• Used in leprosy
• Alternative drug for the treatment of Pneumocystis carinii pneumonia in AIDS patients.