Anti-mycobacteria drugs (Fan)

Question 1

First line anti-TBS drugs

Answer 1

Isoniazid (INH)
Rifampin (RIF), Rifabutin, Rifapentine
Pyrazinamide (PZA)
Ethambutol (EMB)

Question 2

2nd line anti-TBS drugs (drugs, when to use, characteristics)

Answer 2

Ethionamide (ETA)
p-Aminosalicylic acid (PAS)
Cycloserine
Streptomycin, Amikacin, Kanamycin, Capreomycin
Levafloxacin, mofloxacin, gatifloxacin (fluoroquinalones)
Bedaquilline

• Use for multi-resistant TB (resist INH and RIF) or extensively drug resistant TB (resist INH, RIF, fluoroquinolone, aminoglycoside)
• less effective, toxic side effects, expensive

Question 3

Mycobacteria characteristics

Answer 3

Lipid heavy cell wall containing mycolate, arabinogalactan

• ethambutol attacks arabinogalactan synthesis
• INH, ETA, PAS inhibit mycolic acid synthesis

Question 4

Isoniazid (class, treatment, mechanism, side effects)

Answer 4

1st line anti-TB
-used in combo with others except if prophylactic
-INH activated by bacterial KatG to active form (INH-NAD). Inhibits fab1 of FAS-II (bacterial lipid synthesis) to inhibit mycolic acid synthesis by being incorporated in place of NAD
Side effects: hepatitis, peripheral neuropathy (INH looks like pyridoxine, B6, so treat by giving more B6), fever, rash

Question 5

Rifampin (mechanism, spectrum

Answer 5

-1st line antiTB
Also called rifampicin
-inhibits RNA synthesis by binding ß-subunit of RNA polymerase, preventing elongation
-bactericidal for gram +/-, mycobacteria, chlamydia
-Used vs. mycobacteria (TB, leprosy)
-side effects: chills, fever, anemia, tubular necrosis (allergy), hepatitis, nephritis. Induces CYP3A, so excrete other drugs faster.
-PURPLE URINE/SWEAT/TEARS (harmless)

Question 6

Rifabutin/Rifapentine (class, improvements)

Answer 6

derivatives of RIF

-more potent, longer 1/2 lives, better membrane permeability, less CYP3A interaction so less drug interactions

Question 7

Pyrazinamide (PZA) (class, mechanism, spectrum)

Answer 7

• 1st line antiTB
• prodrug converted to active by PcnA
• synergistic with RIF
• bactericidal vs. dormant Mtb by inhibiting transtranslation (tmRNA tags stalled ribosome peptide for degradation to free ribosome, PZA prevents tmRNA binding, so no free ribosomes and defective proteins accumulate, killing dormant bacteria)
• cheap, half life 8-11 hours
• side effects: hepatotoxicity, hyperuricemia, nausea, vomiting

Question 8

Ethambutol (class, mechanism, spectrum)

Answer 8

1st line anti TB
-blocks EmbA/B arabinosyl transferase that incorporate arabinogalactin to Mtb cell wall, weakening wall.
-good vs active Mtb
Side effects: optic neuritis, red-green colorblindness

Question 9

Treatment of TB in HIV patient

Answer 9

• longer, more aggressive dosages

- rifambutin>RIF due to adverse reaction of RIF with antivirals

Question 10

MAC Treatment (m. avium, paratuberculosis, intracellulare)

Answer 10

less susceptible to anti-TB treatment

-azithromycin, clarithromycin, ciprofloxacin, ethambutol, rifabutin