Lecture 36: Tuberculosis [LaCount] Flashcards
What is Tuberculosis and what are some of the things to know about it?
- Mycobacterium Tuberculosis
- Slow Growing & Dormant
- Acid-Fast Bacteria = dye that CANNOT be wash with acid
What is the way that Tuberculosis into the host defenses?
- Macrophages try to kill it but they fail too
What is the Transmission of Tuberculosis?
- ONLY active Tb can be transmitted
- Spread by Speaking, Coughing, Spitting [Aersol Droplets]
What is important about the Pathology of Tuberculosis?
- Granuloma is formed that surrounds the infected macrophages
when it Decays that what causes reactivation
What are some of the Signs and Symptoms of Tuberculosis?
- Productive cought [bloody?], Chest Pain, Fever, Chills, Night Sweats, Weight Loss
What is the difference between Latent & Active in Tubculosis
- Latent: NO symptoms; CANT spread
- Active: HAS symptoms; CAN spread
What is the most common treatment regimen for Tubculosis?
- Rifampin, Isoniazid, Pyrazinamide, Ethamubol [RIPE]
- Alt: Rifapentine, INH, Pyrazinamide, Moxi
What is important to know about Isoniazid?
- Bactericidal
- Prodrug - activated by KatG
What is the MOA of Isoniazid?
- Activated by KatG; acts wiht NAD+/NADP+; inhibits enzymes [InhA] that use NAD+/NADP+
- InhA is a component of FAS II
- = reduction in fatty acids
What is the way that Isoniazid has resistance?
- NO KatG activiation
- TOO MUCH InhA
What are some of the Toxicities of Isoniazid and how does this happen?
- Hepatitis & Peripheral Neuropathy
- 2E1 converts Acetylhydrazine to Hepatotoxic Metabolites
What is important to know about Pyrazinamide?
- Activity depends on pH [Neutral pH = Inactive & low pH = Active]
- Prodrug - needs pncA
What is the MOA for Pyrazinamide?
- Unknown; NOT active with neutral pH, ACTIVE at pH < 5.5, MUST be activated by pncA
- Inhibition of panD and degradation [PZA will stop the PanD pathway = stoping coA precursors]
What is the resistance for Pyrazinmide?
- Mutation in pncA
What are some of the toxicities for Pyrazinamide?
- Joint Pain
- Hepatitis
What is important to know about Ethamutol?
- Bacteristatic
- Synergistic with Rifampin
- NOT use alone
What is the MOA for Ethambutol?
- Inhibits mycobacterial arabinosyl trransferases [basically inhibits layers & messes up the cell wall; Arabinogalactan]
What is important to know about Rifampin?
- MOST EFFECTIVE first line agent
- Can kill inaccessible Tb
- Bactericidal
What is the MOA for Rifampin?
- Binds to RNA polymerase deep within the DNA/RNA channel; basically blocking the path of RNA elongation
Very similar to NNRTIs
What are some of the Side Effects of Rifampin?
- Colored urine, tears, sweat = ORANGE
- VERY potent inducer of CYPs
What are some of the important thing to note about Fluoroquines in Tubculosis?
MOA?
- MOXI, Gati, Levo are the most common
- MOA: Inhibits Topo IV
- Bactericidal
- Can replace Ethambutol
What is the PBaL Regimen?
- Bedaquiline, Pretomanid, Linezolid
- Treats: Extensively Drug-Resistant Tb & Treatment-Tolerant or Non-Responsive Multidrug-Resistant Tb
What is the MOA for Bedaquiline?
- Inhibits ATP Synthase
