TB Tx: Buzz Words and Basics

Question 1

Anti-TB drug cocktail?

Answer 1

Isoniazid
Rifampin
Pyrazinamide
Ethambutol

(Rifabutin and Rifapentine are alternatives to Rifampin)

Question 2

What is a common second-line anti-TB drug?

Answer 2

Streptomycin

Question 3

Where is INH metabolized?

Answer 3

Liver, via acetylation - be aware of fast acetylators, who will have lower concentration of INH in the plasma and a shorter half-life

Question 4

What is a consideration when giving INH to a patient on dialysis?

Answer 4

Give it after dialysis, because it will be removed by dialysis

Question 5

INH adverse effects?

Answer 5

Hepatotoxicity
(bigger risk for pregnant/recent post-partum, EtOH, geriatric, liver dz patients)

Increases AST/ALT

Neuropathy: supplement with B6/pyridoxine to avoid optic neuritis/peripheral neuropathy

Question 6

Orange secretions are associated with which drug?

Answer 6

Rifampin

Question 7

Adverse effects/special considerations with rifampin?

Answer 7

**Potent CYP450 inducer!

Orange secretions

Hepatotoxicity (not as bad as INH)

Flu-like syndromes also possible + rash, fever, n/v; mitigated by intermittent dosing.

Question 8

What drug would warfarin be impacted by, and how?

Answer 8

Rifampin: it is a CYP450 inducer, meaning that it increases the rate of elimination of drugs like warfarin.

INR would decrease (clots more likely) when rate of elimination of warfarin increases during rifampin use.

It goes DOWN, Jules.

Question 9

Patient has Mycobacterium avium complex. Which drug in the cocktail would you switch?

Answer 9

Rifampin –> Rifabutin

Question 10

Adverse effects of ethambutol?

Answer 10

Possible optic neuritis/red-green color blindness (avoid in kids);

hyperurecemia –> gout

Question 11

Adverse effects associated with pyrazinamide

Answer 11

Hepatotoxicity; hyperurecemia –> gout

Question 12

Pharmacokinetic basics of streptomycin

Answer 12

Given IM (not PO)

Mostly renal elimination (maybe better in pt with reduced hepatic function)

Question 13

Adverse effects/considerations with streptomycin?

Answer 13

Nephrotoxicity

Ototoxicity

Hypersensitivity

Congenital deafness (don’t use in pregnancy)

Monotherapy = resistance

Question 14

Preferred LTBI Regimens

Answer 14

Rifampin daily x 4 months
Easiest, caution for drug interactions
Only for HIV neg

2 alternative regimens:

Rifapentine + Isoniazid once/week for 3 months with required DOT
Better completion, but higher cost; ok for HIV+

OR

Rifampin + Isoniazid daily for 3 months
Caution for AE/drug interactions

Question 15

TB Disease Regimen

Answer 15

All 4 drugs (Rif, Inh, Pza, Emb) for 8 weeks (induction period)

Then

Continue just Rif and Inh for 18 weeks, if bacteria is found to be susceptible

Question 16

A patient with afib is stable on warfarin and starts LBTI therapy. What needs to be monitored and why?

Answer 16

Patient’s INR may decrease and be more prone to clots due to the rifampin’s effect as a CYP inducer.

Question 17

Which drug can cause decreased visual acuity and color discrimination?

Answer 17

Ethambutol

Question 18

List 4 factors that could increase risk for INH-induced hepatotoxicity

Answer 18

Alcoholic hepatitis
Concurrent rifampin therapy
Age > 65 YO
Pregnancy/post-partum

Question 19

Which drug is associated with increase serum uric acid?

Answer 19

Ethambutol

Question 20

Which drug is associated with peripheral neuropathy?

Answer 20

Isoniazid

Question 21

Which drug is associated with ototoxicity?

Answer 21

Rifampin and streptomycin

Question 22

Which drug is activated by KatG enzymes in the bacillus?

Answer 22

Isoniazid

Question 23

What should be supplemented when a patient begins 4-drug TB treatment?

Answer 23

Pyridoxine/B6 (to prevent peripheral neuropathy due to INH)

Question 24

Which two TB drugs affect cell wall synthesis, and how do they differ?

Answer 24

Isoniazid inhibits mycolic acid synthesis

Ethambutol inhibits arabinogalactan synthesis

Question 25

What is the MOA of rifampin?

Answer 25

Targets RNA polymerase, inhibits transcription

Question 26

What is the MOA of pryrazinamide?

Answer 26

Targets S1 of 30S ribosomal subunit; works via multiple mechanisms (we’re not totally sure how)

Question 27

What is the MOA and class of streptomycin?

Answer 27

Aminoglycoside: Inhibits protein synthesis

Question 28

Some of the second/third line agents for TB end in -floxacin; what class are they and what is their MOA?

Answer 28

Quinolones: inhibit DNA supercoiling