5-TB Drugs

Question 1

Causative agent of TB & transmission

Answer 1

Mycobacterium tuburculosis; inhalation of aerosolized droplets that reach the lung

Question 2

Populations at risk of TB infection

Answer 2

Homeless, disadvantaged, residents of high-density institutions (jail, nursing home, military), HIV-infected, health care workers
*Patients on TNF-a inhibitors

Question 3

TB screening

Answer 3

PPD: tuberculin Purified Protein Derivative measured in mm 48-72 hours post-placement
*Positive does not distinguish active vs. latent

Question 4

Latent (LTBI) vs. active TB

Answer 4

LTBI: inhalation -> lymphatic uptake of infected macrophages -> hematogenous spread contained by host cell-mediated immunity
Active: progressive multiplication of organisms and inflammation

Question 5

What about known TB with PPD reactions smaller than prescribed cutoff?

Answer 5

Insignificant reaction d/t exposure to non-tuberculous mycobacteria or prior BCG vaccination

Question 6

Blood test for TB

Answer 6

Interferon gamma release assy (IGRA) like QuantiFERON-TB Gold, measures IFN-y production in response to TB antigen

Question 7

Isoniazid (INH) MOA and uses

Answer 7

Inhibits synthesis of mycolic acid (cell wall, provides acid-fast stain)
DOC for LTBI & in combination with others for active infection

Question 8

Isoniazid adverse effects

Answer 8

Increase in liver enzymes in 10-20% people (stop if levels 5x nrl)
Hepatitis rare, increases with age & alcohol use
Peripheral neuropathy - esp. in poor acetylators; always prescribe with B6!

Question 9

Isoniazid drug interactions

Answer 9

Inhibits CYP 2C9 and 2C19, increasing serum levels of warfarin, phenytoin, benzodiazepines
Monitor with periodic serum transaminase levels

Question 10

Isoniazid metabolism

Answer 10

Metabolized by conjugation with acetyl-CoA by acetyltransferase enzyme
Genetically determined rate, slow acetylation is AR trait (50% US population)

Question 11

Rifampin MOA and uses

Answer 11

Inhibits bacterial RNA polymerase

Alternative single tx for LTBI, or in combination therapy for active infection (never alone because may -> resistance)

Question 12

Rifampin adverse effects

Answer 12

Flu-like illness (up to 5% intermittent users)
Potential hepatic toxicity (esp w/ EtOH)
Red-orange color of urine, tears, saliva, contact lens

Question 13

Rifampin drug interactions

Answer 13

Potent inducer of multiple CYP450 enzymes, increases metabolism of many drugs (inc HIV drugs) - monitor with liver function tests, thrombocytopenia, acute renal failure
*Biggest drawback to using this drug is the interactions

Question 14

Rifabutin

Answer 14

Newer rifamycin derivative of rifampin with same MOA/ADR; least potent CYP450 inducer of rifamycin class
Preferential use in HIV patients

Question 15

Rifapentine

Answer 15

Newer rifamycin derivative of rifampin with same MOA/ADR; intermediate drug interaction potential (between rifampin, rifabutin)
Given once weekly in selected patients

Question 16

Pyrazinamide MOA & uses

Answer 16

MOA unknown

Used in combo therapy for active infections to allow reduction of tx duration

Question 17

Pyrazinamide ADR & drug reactions

Answer 17

ADR: hepatotoxicity (esp w/ rifampin), hyperuricemia, gout
DI: blocks hypouricemic action of allopurinol
*Monitor w liver fxn tests, uric acid

Question 18

Ethambutol MOA & uses

Answer 18

Impairs bacterial metabolism

In combo therapy for active infections

Question 19

Ethambutol ADR & drug rxns

Answer 19

ADR: optic neuritis at high doses; red-green color blindness (monitor acuity and color vision before start of therapy and each month)
DI: none

Question 20

Recommended tx of LTBI

Answer 20

1st line: INH 5 mg/kg/day for 9 months
OR INH 15 mg/kg twice weekly with DOT (directly observed therapy) for 9 months
OR INH 15 mg/kg + rifapentine 300-900 mg weekly for 12 wk with DOT (only pts >12)
2nd line: rifampin 600mg/d for 4 mo if INH-resistant strain suspected or confirmed

Question 21

Confirming an active TB infection

Answer 21

High index of suspicion -> positive AFB smear and/or positive sputum cultures for M. tuberculosis

Question 22

Recommended tx for active drug-susceptible TB

Answer 22

1st phase: INH + rifampin + pyrazinamide + ethambutol for 2 mos

2nd: INH + rifampin for 4-7 mos (depends on initial presentation)
* Completion = # doses taken, not duration

Question 23

Recommended tx for active drug-resistant TB

Answer 23

Clinical specialist referral

Possible: aminoglycosides, FQs, capreomycin, aminosalicylic acid, cycloserine, ethionamide

Question 24

Multi-drug resistant TB (MDRTB) resistance and tx

Answer 24

Res to INH & rifampin

Tx with 5-7 drugs

Question 25

Extensively drug-resistant TB (XDRTB) resistance and tx

Answer 25

Res to INH, rifampin, FQs, & one of: capreomycin, kanamycin, or amikacin *Tx with 6 drugs continues for 18-24 months or 12-18 months after negative culture

Question 26

Drug regimen for XDRTB

Answer 26

Pyrazinamide &/or ethambutol + 1 FQ (gati-, levo-, moxi-floxacin) + 1 injectable (amikacin, capreo-, strepto-, kana-mycin) + oral second line (cycloserine, ethionamide, para-aminosalicylic acid) + if needed, one or more 3rd line (clofazimine, linezolid, amoxacillin-clavulanate, imipenem, macrolide, high-dose INH)

Question 27

Adverse effects of anti-TB treatment

Answer 27

GI upset (take with food), drug interactions (esp rifampin), drug-induced hepatitis (INH, RIF, PZA; esp in hx of hep or EtOH abuse), and others (rifampin: thrombocytopenia, acute renal failure; ethambutol: optic neuritis)

Question 28

Risk category C drugs

Answer 28

INH, rifampin, ethambutol, pyrazinamide, capreomycin

Question 29

Risk category D drugs

Answer 29

Streptomycin