Mycobacterial Flashcards
M. tuberculosis
rod, lipid rich wall (mycolic acid), poor gram stain (Acid-Fast pink)
Intracellular - drugs must get inside cell
Slow growing; drug resistant is concern
Latent TB
Inactive - contained tubercle bacilli in body TST/blood test positive normal CXR negative sputum No symptoms Not infectious
TB Disease
Active - multiplying tubercle bacilli in body TST/blood test positive abnormal CXR positive sputum Cough, fever, weight loss Infectious before treatment
Preferred Initial Therapy for active TB
Isoniazid, Rifampin, Pyrazinamide, Ethambutol
Preferred Continuation Therapy for active TB
Isoniazid, Rifampin
Latent TB therapy
Isoniazid
MOA of Isoniazid
bactericidal for actively growing bacilli - penetrates into macrophages (intracellular/extracellular)
Inhibits synthesis of mycolic acid (cell wall) - forms bond with proteins in synthesis
Prodrug
RES of Isoniazid
Mutation in Kat G = decreased activation
Overexpression of Inh A protein (mycolic acid synthesis)
Rapid resistance = 2 agents required to treat active
AE Isoniazid
Hepatitis - increased with age and alcohol dependence
Peripheral neuropathy - structurally similar to vitamin B6 - reversed by low dose B6
MOA Rifampin
Inhibits transcription - binds RNA polymerase
Penetrates tissue/phagocytic cells (intracellular)
RES Rifampin
point mutation in bacterial RNA polymerase
Use in combination
AE Rifampin
induces cytochrome p450 = increases elimination of drugs
Impacts metabolism of anti-retrovirals
What to give HIV patient with TB?
Rifabutin instead of Rifampin
MOA Pyrazinamide
Potential inhibitor of mycolic acid - dependent on acidic environment
Used ONLY in active TB
Prodrug
RES Pyrazinamide
mutation in enzyme for activation