Tuberculosis pharmacology/therapeutics

Question 1

how is tuberculosis spread

Answer 1

through the air in droplets

Question 2

extrapulmonary tuberculosis

Answer 2

• tuberculosis infection that spreads beyond the lungs

- makes up about 15% of cases

Question 3

mycobacterium tuberculosis features

Answer 3

• gm+
• mycolic acids make up outer membrane
• slow growing
• resides in macrophages
• rapidly develop resistance

Question 4

what do drugs target in TB

Answer 4

cell wall/FAS

Question 5

symptoms of active TB

Answer 5

• productive prolonged cough
• coughing up blood
• chest pain
• fever
• night sweats
• easily fatigued
• unexplained weight loss

Question 6

symptoms of latent TB

Answer 6

• no obvious symptoms

- granulomatous lesions in lung

Question 7

positive TST(PPD) for HIV infected/immunocompromised

Answer 7

> 5 mm

Question 8

positive TST(PPD) for high risk or injection drug user

Answer 8

> 10 mm

Question 9

positive TST(PPD) for person with no risk factors

Answer 9

> 15 mm

Question 10

TB vaccine

Answer 10

BCG

lasts 10-20 years

Question 11

drug susceptibility test

Answer 11

MODS assay using sputum samples grows faster than normal cultures

Question 12

1st line regimen for active TB infection

Answer 12

2 months: rifampin, isoniazid, pyrazinamide, ethambutol

then 4 months of: rifampin, isoniazid

Question 13

isoniazid moa

Answer 13

inhibits biosynthesis of mycolic acids by binding to NAD to prevent elongation

Question 14

isoniazid ADME

Answer 14

• rapidly absorbed
• t1/2 depends on fast or slow acetylators (1-3 hours)
• inhibits hepatic enzymes

Question 15

isoniazid adverse effects

Answer 15

• peripheral neuropathy due to interference with pyridoxine (B6) metabolism, can be averted by Vit B6 supplements
• rarely hepatitis
• inhibits hepatic enzymes

Question 16

rifampin moa

Answer 16

binds to beta-subunit of bacterial DNA dependent RNA polymerase preventing synthesis

Question 17

rifampin ADME

Answer 17

• lipid-soluble
• t1/2 of 2-3 hours
• induces and inhibits 3A4

Question 18

rifampin adverse effects

Answer 18

• reddish coloration of urine, tears, saliva
• flu like symptoms
• thrombocytopenia

Question 19

rifampin drug interactions

Answer 19

• oral anticoagulants
• oral contraceptives
• methadone
• will need dosage changes*

Question 20

ethambutol moa

Answer 20

inhibits cell wall by preventing mycolic acids from attaching to arabinogalactan

Question 21

ethambutol ADME

Answer 21

t1/2 = 3-4

Question 22

ethambutol adverse effects

Answer 22

optic neuritis that can lead to blindness if drug isn’t stopped

Question 23

pyrazinamide moa

Answer 23

binds ribosomal protein

only in pH

Question 24

pyrazinamide ADME

Answer 24

half life of 10 hours

Question 25

pyrazinamide adverse effects

Answer 25

- GI intolerance | - occasionally gout

Question 26

multidrug resistant TB treatment

Answer 26

at least 4 effective drugs for 18-24 months

Question 27

risk that a person will have active TB in life time

Answer 27

10%

Question 28

how does PPD test work

Answer 28

tuberculin is injected and if the body has been exposed to TB the T cells are sensitized and mount a response

Question 29

recent converter

Answer 29

based on reading 2 years ago: for <35 PPD increases by more than 10 mm for >35 PPD increases by >15 mm

Question 30

who is at greatest risk of converting latent TB to active

Answer 30

- weak immune systems | - starting steroid use

Question 31

isoniazid prophylactic dose in none HIV

Answer 31

300 mg qd for 9 months

Question 32

isoniazid prophylactic dose in HIV patients

Answer 32

300 mg qd for at least 12 months

Question 33

rifampin prophylactc dose

Answer 33

600 mg qd for 4 months

Question 34

what needs to be added to regimen in isoniazid based regimens for those at risk for neuropathy

Answer 34

pyridoxine (B6) 25 mg qd

Question 35

workup for active TB

Answer 35

- signs and symptoms - chest xray - 3 morning sputum samples - PPD

Question 36

stain to see mycobacteria

Answer 36

acid fast bacilli stain of sputum, not culture

Question 37

treatment regimen for active TB initial phase

Answer 37

always 4 drugs for 8 weeks with pyridoxine

Question 38

if after initial treatment phase cavitation OR AFB positive

Answer 38

begin continuation phase as isoniazid and rifampin for 4 months

Question 39

if after initial treatment phase cavitation AND culture positive

Answer 39

isoniazid and rifampin for 7 months

Question 40

overall active TB treatment timing

Answer 40

-initial phase 2 months -continuation phase 4-7 months total = 6-9 months

Question 41

those at highest risk for neuropathy when taking isoniazid

Answer 41

``` DM alcoholics malnourished HIV pregnancy seizures ```

Question 42

isoniazid INH

Answer 42

- inhibit hepatic enzyme - neuropathy - hepatitis

Question 43

drug that can cause thrombocytopenia

Answer 43

rifampin

Question 44

what to do if hepatitis occurs

Answer 44

- stop isoniazid, rifampin, pyrazinamide - regimen with ethambutol and other abx - restart 1st lines when AST <2x upper limit of normal

Question 45

2nd line agents

Answer 45

``` kanamycin viomycin capreomycin amikacin streptomycin levofloxacin cycloserine ethionamide ```

Question 46

former 1st line agent that is now 2nd line

Answer 46

streptomycin due to ototoxicity

Question 47

what to do if resistant bugs are resistant to a drug

Answer 47

replace with at least 2 drugs it is susceptible to

Question 48

how to deal with GI distress

Answer 48

- take with food or change dosing hour | - DO NOT split dosing (cutting tablets)