Antimycobacterials Flashcards
Which two drugs are the most powerful bactericidal drugs active against all TB bacilli?
Rifampicin
Isoniazid
Ethambutol is bactericidal/bacteriostatic
Bacteriostatic
Pyrazinamide is bactericidal/bacteriostatic
Bactericidal
Give the 1st line treatment for TB
2 months RIPE
4 months RI
Why does TB have combination therapy?
To decrease resistance
To kill intracellular AND extracellular forms
Comment on the properties of isoniazid
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
Comment on the properties of rifampicin
Bactericidal against
- actively growing TB
- intracellular slowly replicating bacilli
- nearly dormant organisms (some activity)
MOA: disrupts RNA synthesis
Well absorbed orally
Penetrates CSF
Comment on the properties of ethambutol
Bacteriostatic in vitro/within macrophages
MOA: interferes with cell wall biosynthesis
Comment on the properties of pyrazinamide
Bactericidal against semi-dormant organisms in acid pH environment (phagolysosome)
MOA: inhibits cell wall synthesis
Well absorbed orally
Liver metabolism
Name 2nd line TB agents
Para-aminosalicylic acid Cycloserine Terizidone Ethionamide Clofazimine Linezolid Fluoroquinolones
What is the target site of para-aminosalicylic acid?
Folate synthesis
What is the target site of cycloserine?
Cell wall synthesis
What is the target site of terizidone?
Cell wall synthesis
What is the target site of ethionamide?
Mycolic acid synthesis
What is the target site of clofazimine?
Cell wall synthesis
What is the target site of linezolid?
Protein synthesis
What is the target site of fluoroquinolones
DNA gyrase
What was bedaquiline previously known as?
TMC207
What is the target site of bedaquiline?
Proton pump inhibition of mycobacterial ATP synthase
Name the main side effect of bedaquiline
Prolonged QT interval
What was delamanid previously known as?
Deltyba
OPC-67683
What is the target site of delamanid?
Mycobacterial cell wall synthesis
Name the main side effect of delamanid
QT prolongation
Which two drugs must not be included in the treatment of MDR TB?
Kanamycin
Capreomycin
Discuss the MDR TB treatment regimen options
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
Discuss the initiation phase of modified short MDR TB treatment regimen
Bedaquiline Levofloxacin LZD Ethambutol PZA Clofazimine High dose INH
Discuss the continuation phase of modified short MDR TB treatment regimen
5months Clofazimine Levofloxacin Ethambutol PZA
Which new treatment drug is used for XDR TB?
Pretomanid
