TB

Question 1

Bedaquiline (TMC-207)

MOA?

Treatment?

Answer 1

Question 2

Properties of Rifampin?

DMPK

Metabolism

Excretion?

Answer 2

Question 3

Ethambutol

Only used for?

Static or Cidal?

MOA?

Resistance?

DMPK?

Major Toxicity?

Answer 3

Question 4

How resistant is Restistant TB?

TB

MDR TB

Definition and second line

XDR TB

Answer 4

Question 5

First line treatment of TB needs to do what?

Answer 5

• Block the synthesis of Mycolic Acid and arabinogalactans

Question 6

Standard TB Tx

TB exists in 3 portions:

Six month treatment (___)

7 points

Rationale for Therapeutic Combos

Multiple Targets?

Resistance

Toxicities

Answer 6

• At cell wall mycolic acid and arabanogalactan layer, transcription and translation
• High levels of resistance 3 to 4 durgs to overcome this
• Puts stress on the liver

Question 7

Isoniazide (INH)

DMPK: Administration?

Distributes on an empty?

Toxicity?

MOA?

Resistance?

Answer 7

Question 8

Pyrazinamide (PZN)

Static or cidal?

DMPK

MOA?

3 things

Toxicity?

Resistance?

Answer 8

Question 9

TB drugs in development

Answer 9

Question 10

Rifabutin and Rifaximin?

___ Macrolides?

Treatment of?

Rifaximin absorption admin, treats, alternative for?

Answer 10

Question 11

Clinical properties of Rifampin

Usage

Prophylactic usage?

Toxicities?

Interactions?

Answer 11

Question 12

Second line and alternative therapies for TB

Answer 12

• Unique second line
  
  • Ethionamide, Cycloserine, PAS, Capremycin, Bedquiline
• Antibiotic classes already discussed
  
  • FQs (levo, oflo, Moxi)
  • AGs (kanamycin, amikacin, streptomycin)
  • COmbo therapy needs (INH, Pyrazinamide, ethambutol)

Question 13

INH is a ____ that gets converted by ____ then it can inhibit ___

Resistance is common with?

Answer 13

• Prodrug that eventually gets coverted by KatG then it can inhibit INHa
• Mutations in both of these sites pose problems

Question 14

Schematic Diagram of Mycobacterial Cell wall

Or at least the parts that are targeted for TB

8 parts

Answer 14

Question 15

Rifampin

Color?

Sensitive to?

MOA?

Static or Cidal?

Spectrum?

Resistance?

Answer 15

Question 16

Second line agents cycloserine and p-aminosalicylic acid (PAS)

Cycloserine MOA, resistance, spectrum

Pamino- Inhibits?, Resistance?

Answer 16

Question 17

Ethionamide

Answer 17

• Similar MOA to INH (mycolic acid synthesis inhibition)
• Only effective against mycobacterium
• Resistance is fast

Question 18

Second line Capreomycin

MOA

static or cidal?

Admin?

Resistance?

Toxicity?

Answer 18

Question 19

Mechanism of action of PZN

Answer 19

• Mechanism of action of pyrazinamide (PZA). PZA enters the bacilli by passive diffusion and is then converted by the nicotinamidase PncA into pyrazinoic acid (POA). POA exits the cell by passive diffusion, as well as by an efflux mechanism, which is not yet well characterized. In their revised mechanism, Zhang and co‐workers show that POA binds RpsA and blocks trans‐translation. Note: for simplicity, only the inner membrane of the mycobacterial cell envelope is depicted.