Drugs Used To Treat Tb

Front 1

What is indicative of a positive PPD test?

Back 1

Induration of the tissue mediated by a type IV delayed hypersensitivity reaction

Front 2

What is the IFN-gamma test to diagnose TB?

Back 2

Test quantifies the synthesis of IFN-gamma by sensitized T-cells in response to challenge with PPD

Front 3

Does a positive PPD mean the patient has latent TB?

Back 3

No, it just means that the patient has TB --> test does not differentiate latent from active disease

Front 4

What is the MOA of Isoniazid?

Back 4

INH is a prodrug which is converted to its active form by the mycobacterial catalase-peroixdase

Active INH prevents the synthesis of Mycolic acid
(component of mycobacterium cell wall)

Front 5

How does the active INH metabolite prevent the synthesis of mycolic aicd?

Back 5

Binds covalently to the acyl carrier protein and the b-ketoacyl carrier protein synthetase

Front 6

INH is ______________ for latent (non-dividing) Mycobacterium, but it kills bacilli which are dividing rapidly

Back 6

Bacteriostatic

Front 7

Why is INH NEVER used as a single agent in the treatment of ACTIVE TB?

Back 7

Rapid development of bacterial resistance

Front 8

In healthy patients with a positive PPD, how many months of Isoniazid treatment is required?

Back 8

9 months

Front 9

Can INH be used as a single agent to treat patients who have a positive PPD and a negative chest X-ray?

Back 9

Yes

Front 10

What percent of patients with a positive PPD and a negative CXR that don't receive INH will develop tubercular disease at some time in their life?

Back 10

5-15%

Front 11

INH for 9 months reduces the probability of PPD+ converters from developing active disease by ______

Back 11

50%

Front 12

INH is metabolized by hepatic ______________ and _______ acetylators are thought to be at increased risk for hepato- and neurotoxicity?

Back 12

N-acetylation

Slow

Front 13

Should a patient discontinue INH if they exhibit a 3-4X increase in ALT and AST?

Back 13

No

Front 14

What drug should be used if a patient is 35+ y.o. & the date of seroconversion (TB) is unknown?

Back 14

Rifampin

Front 15

Intake of ___________ increases hepatotoxicity caused by INH?

Back 15

ChaCho's margaritas

Front 16

INH antagonizes the enzymatic reactions which use ____________ as a cofactor?

Back 16

Pyridoxine (vitamin B6)

Front 17

What is the effect of INH antagonism of the reactions that use Pyridoxine as a co-factor?

How is this condition treated?

Back 17

Peripheral neuropathy

Daily dose of Vitamin B6 prevents and reverses this neuropathy

Front 18

What kind of patients do you give B6 to that are taking INH b/c of a positive PPD and negative CXR?

Back 18

Patients predisposed to neuropathy:

-pregnant women, patients w/ diabetes mellitus, uremia, malnutrition, HIV or seizures

Front 19

What is the MOA of Rifampin and Rifabutin?

Back 19

Inhibit mRNA synthesis by binding to the beta-subunit of the bacterial DNA-dependent-RNA polymerase

*drugs do not bind to human RNA pol

Front 20

Are Rifampin & Rifabutin bactericidal or bacteriostatic?

Back 20

Bactericidal --> easily penetrate tissues to kill intracellular mycobacteria and bugs in abscesses

Front 21

Why is Rifampin never used as a single agent in the treatment of active TB?

Back 21

b/c of the development of bacterial resistance

Front 22

Rifampin is a strong inducer of ____________ and enhances the clearance of drugs used to treat _____ infections

Back 22

CYP450

HIV

*protease inhibitors and NNRTIs

Front 23

What drug is used in HIV + patients with TB due to a 50% reduction of CYP induction compared to Rifampin?

Back 23

Rifabutin

Front 24

Drug regimens with Rifampin clear the sputum of mycobacteria about ______ weeks faster than those w/o Rifampin

Back 24

Two

Front 25

Rifampin can be used as an alternative for INH prophylaxis of TB. How long is treatment required for?

Back 25

Four months

Front 26

What other activities does Rifampin have?

Back 26

1. Meningococci (elimination of carrier state)

2. Pneumococci (PCN resistant)

3. Staph (MRSA)

Front 27

What are the toxicities of Rifampin?

Back 27

1. Urine, skin saliva, tears, and skin turn orange
2. Flu-like syndrome
3. Hepatitis w/ elevated LFT's
4. Drug-Drug interactions--increase the hepatic clearance of other drugs

Front 28

What pregnancy category are INH and Rifampin?

Back 28

Catergory C

*benefits should exceed the risk to the fetus

Front 29

What are the S/E of Rifabutin?

Back 29

Yellow discoloration of the skin
Polymyalgias
Uveitis

Front 30

What is the MOA of Pyrazinamide?

Back 30

Unknown--but kills semi-dormant, intracellular bacilli in macrophages

Front 31

What is the therapeutic use of Pyrazinamide?

Back 31

Part of the RIPE combination for active TB treatment

Front 32

What % of the isolates resistant to INH-Rifampin are resistant to PZA?

Back 32

50%

Front 33

What are the toxicities of PZA?

Back 33

N/V
Hepatotoxicity (1-5%)
No drug-drug interactions

Front 34

What is the MOA of Ethambutol?

Back 34

Bacteriostatic against actively growing TB bacilli via inhibition of arabinosyl transferase--an enzyme which polymerizes arabinoglycan

Arabinoglycan is a component of the mycobacterial cell wall, so ethambutol inhibits cell wall synthesis

Front 35

What are the therapeutic uses of Ethambutol?

Back 35

Part of the RIPE combination for active TB treatment

Front 36

What % of the isolates resistant to INH-Rifampin are resistant to Ethambutol?

Back 36

80%

Front 37

What are the toxicities associated with Ethambutol?

Back 37

1. Ocular damage--retrobulbuar neuritis
(impaired vision abnormal red/green vision; get vision exam b4 therapy_

2. No drug-drug interactions

Front 38

What is the MOA of Streptomycin?

Back 38

Aminoglycoside drug that inhibits bacterial protein synthesis

Acts primarily against extracellular bacteria

Front 39

What are the Clinical uses of Streptomycin?

Back 39

1. i.m. or i.v. to treat patients w/ mycobacterial meningitis or disseminated infection

2. 80% of isolates resistant to INH-rifampin are resistant to streptomycin

3.Sometimes replaces EMB in the INH-rifampin-PZA regimen

Front 40

What are the toxicities of Streptomycin?

Back 40

Greater VESTIBULAR toxicity
(in comparison to other aminoglycosides)

LESS auditory and renal toxicity

Front 41

What drugs are used to treat MDR TB?

Back 41

Ciprofloxacin & Levofloxacin

Moxifloxacin shows the greatest activity against TV