TB drugs

Question 1

MOA: binds to the beta subunit (rpoB) of DNA-dependent RNA polymerase suppressing chain formation in RNA synthesis
Inhibits most gram-positive bacteria as well as E coli, Pseudomonas, Proteus & Klebsiella; very active against S aureus; Legionella, N meningitidis and H flu

Answer 1

Rifamycins

1. Rifampin
2. Rifabutin -> induces CYP less & is used in HIV pts
3. Rifapentine -> long-acting & taken with food

Interactions: CYP induction

Adverse: red-man syndrome

Question 2

MOA: Targets mycobacterial fatty acid synthase I gene in mycolic acid biosynthesis & shortens course of TB treatment; activated by acidic conditions; kills within mycobacterium protected areas (within macrophages)

Answer 2

pyrazinamide

Resistance: PZase gene mutation

Adverse: inhibits urate secretion -> gout

Question 3

MOA: enters by passive diffusion and is activated by KatG (catalase-peroxidase) to produce NAD isomer which prevents activation of enzymes in the synthesis of mycolic acid (InhA and KasA)

Answer 3

isoniazid

Adverse: peripheral neuropathy (give pyridoxine (B6)); hepatitis

Ethionamide is like this but activated by a different enzyme so not affected by KatG mutations

Question 4

MOA: inhibits arabinosyl transferase III, disrupting arabinose into arabinogalactan biosynthesis, disrupting assembly of cell wall (linker for mycolic acid to peptidoglycan)
Use: isoniazid-resistant TB

Answer 4

Ethambutol

Adverse: red-green colorblindness

Note: replace Streptomycin with Ethambutol if it isn’t working

Question 5

MOA: structural analog of d-alanine

used as second-line TB tx

Answer 5

Cycloserine

Adverse: “psych-serine”

Question 6

MOA: structural analog to PABA

second-line for TB tx

Answer 6

Aminosalicylic acid (PAS)

Question 7

MOA: inhibition of protein synthesis by binding to 30s ribosomal subunit

Use: multidrug resistant TB

Answer 7

Capreomycin

Adverse: deafness