Antimycobacterials

Question 1

Which two drugs are the most powerful bactericidal drugs active against all TB bacilli?

Answer 1

Rifampicin

Isoniazid

Question 2

Ethambutol is bactericidal/bacteriostatic

Answer 2

Bacteriostatic

Question 3

Pyrazinamide is bactericidal/bacteriostatic

Answer 3

Bactericidal

Question 4

Give the 1st line treatment for TB

Answer 4

2 months RIPE

4 months RI

Question 5

Why does TB have combination therapy?

Answer 5

To decrease resistance

To kill intracellular AND extracellular forms

Question 6

Comment on the properties of isoniazid

Answer 6

Bactericidal against actively growing TB
Bacteriostatic against non-replicating organisms
MOA: inhibits synthetic pathways of mycolic acid + activate by catalase peroxidase
Well absorbed orally
Liver metabolism

Question 7

Comment on the properties of rifampicin

Answer 7

Bactericidal against
- actively growing TB
- intracellular slowly replicating bacilli
- nearly dormant organisms (some activity)
MOA: disrupts RNA synthesis
Well absorbed orally
Penetrates CSF

Question 8

Comment on the properties of ethambutol

Answer 8

Bacteriostatic in vitro/within macrophages

MOA: interferes with cell wall biosynthesis

Question 9

Comment on the properties of pyrazinamide

Answer 9

Bactericidal against semi-dormant organisms in acid pH environment (phagolysosome)
MOA: inhibits cell wall synthesis
Well absorbed orally
Liver metabolism

Question 10

Name 2nd line TB agents

Answer 10

Para-aminosalicylic acid
Cycloserine
Terizidone
Ethionamide
Clofazimine
Linezolid
Fluoroquinolones

Question 11

What is the target site of para-aminosalicylic acid?

Answer 11

Folate synthesis

Question 12

What is the target site of cycloserine?

Answer 12

Cell wall synthesis

Question 13

What is the target site of terizidone?

Answer 13

Cell wall synthesis

Question 14

What is the target site of ethionamide?

Answer 14

Mycolic acid synthesis

Question 15

What is the target site of clofazimine?

Answer 15

Cell wall synthesis

Question 16

What is the target site of linezolid?

Answer 16

Protein synthesis

Question 17

What is the target site of fluoroquinolones

Answer 17

DNA gyrase

Question 18

What was bedaquiline previously known as?

Answer 18

TMC207

Question 19

What is the target site of bedaquiline?

Answer 19

Proton pump inhibition of mycobacterial ATP synthase

Question 20

Name the main side effect of bedaquiline

Answer 20

Prolonged QT interval

Question 21

What was delamanid previously known as?

Answer 21

Deltyba

OPC-67683

Question 22

What is the target site of delamanid?

Answer 22

Mycobacterial cell wall synthesis

Question 23

Name the main side effect of delamanid

Answer 23

QT prolongation

Question 24

Which two drugs must not be included in the treatment of MDR TB?

Answer 24

Kanamycin

Capreomycin

Question 25

Discuss the MDR TB treatment regimen options

Answer 25

``` Group A - levofloxacin/moxifloxacin - bedaquiline - linezolid Group B - clofazimine - cycloserine/terizidone Group C - ethambutol - delamanid - pyrazinamide - imipenem-cilastatin/meropenem - amikacin/streptomycin - ethionamide/prothionamide - p-aminosalicylic acid ```

Question 26

Discuss the initiation phase of modified short MDR TB treatment regimen

Answer 26

``` Bedaquiline Levofloxacin LZD Ethambutol PZA Clofazimine High dose INH ```

Question 27

Discuss the continuation phase of modified short MDR TB treatment regimen

Answer 27

``` 5months Clofazimine Levofloxacin Ethambutol PZA ```

Question 28

Which new treatment drug is used for XDR TB?

Answer 28

Pretomanid