TB Tx

Question 1

Most effective and compliant latent TB Tx

Answer 1

Best: Isoniazid and Rifapentine w/ directly observed therapy for 3 months

Not recommended:
age under 2, pregnant, HIV on anti-virals

Question 2

Latent TB Tx Regimens

Answer 2

Isoniazid
6 months - daily or twice weekly*
9 months - daily or twice weekly*

Isoniazid & Rifapentine
3 months - once weekly*

Rifampin
4 months - daily

Question 3

Active TB Regimen

Answer 3

Initial: RIPE daily for 8 weeks
Rifampin
Isoniazid
Pyrazinamide
Ethambutol

Continuation: Rifampin/Isoniazid daily or twice weekly for 18 weeks
- HIV pts: Rifapentine/Isoniazid once a week
must have no cavities on CXR and have - AFB smears

Question 4

Isoniazid

Answer 4

MOA: interrupts mycolic acid synthesis of cell wall
- bactericidal: rapidly dividing organisms
- bacteriostatic: organisms within close caseous lesions
Resistance: decreased uptake, alteration/overproduction of target enzyme
- never use as a single agent in active dx!
PK/PD: induces CYP, can impact concurrent CYP substrate therapy
AE: peripheral neuropathy (vitamin B6 supplementation), hepatotoxicity (esp. w/ rifampin) , joint pain, photosensitivity, facial rash
Interactions: antacids, take 1 hr before
**induces CYP2E1 to produce more toxic metabolite from tylenol

Question 5

Rifampin

Answer 5

MOA: bind beta subunit of RNA polymerase to inhibit RNA synthesis
- bactericidal
Resistance: alteration of beta subunit of RNA poly, drug can no longer bind
- never use a single agent
PK/PD: penetrates CSF, no adjustment needed for renal insufficiency
AE: orange-red body fluids, hepatotoxicity (w/ predisposed risk factors), induces CYP450 (reduces half-life of prednisone, propanodol, sulfonamides. dapsone, ketoconazole, HIV protease inhibitors, NNRTIs), decreased effectiveness of oral contraceptives and anticoagulants

Other uses: MRSA, S. epidermidis, meningitis, staph fron nasal carriers, antileprosy

Question 6

HIV-alternative drugs

Answer 6

Use rifabutin instead of rifampin

- less effect on metabolism of HIV pts on protease inhibitors

Question 7

Ethambutol

Answer 7

MOA: disrupts cell wall synthesis
- inhibit arabinosyl transferase
Resistance: slow development
PK/PD: significantly excreted through kidneys, reduce dose with renal insufficiency
AE: optic neuritis = decreased visual acuity and loss of color discrimination (test for visual disturbances prior to and during therapy)

Question 8

pyrazinamide

Answer 8

MOA: decreases pH below threshold for growth, active against tubercle bacilli in macrophage
PK/PD: adjust dose with severe renal insufficiency
AE: arthalgia (pain in joints), acute gout, hepatotoxicity