Lecture 36: Tuberculosis [LaCount]

Question 1

What is Tuberculosis and what are some of the things to know about it?

Answer 1

• Mycobacterium Tuberculosis
• Slow Growing & Dormant
• Acid-Fast Bacteria = dye that CANNOT be wash with acid

Question 2

What is the way that Tuberculosis into the host defenses?

Answer 2

• Macrophages try to kill it but they fail too

Question 3

What is the Transmission of Tuberculosis?

Answer 3

• ONLY active Tb can be transmitted
• Spread by Speaking, Coughing, Spitting [Aersol Droplets]

Question 4

What is important about the Pathology of Tuberculosis?

Answer 4

• Granuloma is formed that surrounds the infected macrophages

when it Decays that what causes reactivation

Question 5

What are some of the Signs and Symptoms of Tuberculosis?

Answer 5

• Productive cought [bloody?], Chest Pain, Fever, Chills, Night Sweats, Weight Loss

Question 6

What is the difference between Latent & Active in Tubculosis

Answer 6

• Latent: NO symptoms; CANT spread
• Active: HAS symptoms; CAN spread

Question 7

What is the most common treatment regimen for Tubculosis?

Answer 7

• Rifampin, Isoniazid, Pyrazinamide, Ethamubol [RIPE]
• Alt: Rifapentine, INH, Pyrazinamide, Moxi

Question 8

What is important to know about Isoniazid?

Answer 8

• Bactericidal
• Prodrug - activated by KatG

Question 9

What is the MOA of Isoniazid?

Answer 9

• 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

Question 10

What is the way that Isoniazid has resistance?

Answer 10

• NO KatG activiation
• TOO MUCH InhA

Question 11

What are some of the Toxicities of Isoniazid and how does this happen?

Answer 11

• Hepatitis & Peripheral Neuropathy
• 2E1 converts Acetylhydrazine to Hepatotoxic Metabolites

Question 12

What is important to know about Pyrazinamide?

Answer 12

• Activity depends on pH [Neutral pH = Inactive & low pH = Active]
• Prodrug - needs pncA

Question 13

What is the MOA for Pyrazinamide?

Answer 13

• 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]

Question 14

What is the resistance for Pyrazinmide?

Answer 14

• Mutation in pncA

Question 15

What are some of the toxicities for Pyrazinamide?

Answer 15

• Joint Pain
• Hepatitis

Question 16

What is important to know about Ethamutol?

Answer 16

• Bacteristatic
• Synergistic with Rifampin
• NOT use alone

Question 17

What is the MOA for Ethambutol?

Answer 17

• Inhibits mycobacterial arabinosyl trransferases [basically inhibits layers & messes up the cell wall; Arabinogalactan]

Question 18

What is important to know about Rifampin?

Answer 18

• MOST EFFECTIVE first line agent
• Can kill inaccessible Tb
• Bactericidal

Question 19

What is the MOA for Rifampin?

Answer 19

• Binds to RNA polymerase deep within the DNA/RNA channel; basically blocking the path of RNA elongation

Very similar to NNRTIs

Question 20

What are some of the Side Effects of Rifampin?

Answer 20

• Colored urine, tears, sweat = ORANGE
• VERY potent inducer of CYPs

Question 21

What are some of the important thing to note about Fluoroquines in Tubculosis?

MOA?

Answer 21

• MOXI, Gati, Levo are the most common
• MOA: Inhibits Topo IV
• Bactericidal
• Can replace Ethambutol

Question 22

What is the PBaL Regimen?

Answer 22

• Bedaquiline, Pretomanid, Linezolid
• Treats: Extensively Drug-Resistant Tb & Treatment-Tolerant or Non-Responsive Multidrug-Resistant Tb

Question 23

What is the MOA for Bedaquiline?

Answer 23

• Inhibits ATP Synthase