JAL L1 TB

Question 1

What organism is the cause of TB?

Answer 1

Mycobacterium tuberculosis

Question 2

TB is a major opportunistic infection in whom?

Answer 2

AIDs patients, children

Question 3

What caused the most dramatic decrease in TB numbers so far?

Answer 3

improvements in living conditions

Question 4

what sort of thing is Mycobacterium tuberculosis

Answer 4

a slow growing bacillus

Question 5

why is M. TB resistant to weak disinfectants?

Answer 5

cell wall is rich in lipids - very hydrophobic which prevents it drying out

Question 6

There are 3 other strains that can cause TB:

Answer 6

M. bovis
M. africanum
M. microti

Question 7

What happens when bacilli droplets are inhaled?

Answer 7

They are phagocytosed by macrophages, but this DOES NOT destroy them

Question 8

Why can’t macrophages destroy TB?

Answer 8

It never fuses with the lysosome - we don’t know why, something to do with the bacterial cell wall

Question 9

How long does TB sit in the macrophage? What is it doing there?
What happens next?

Answer 9

7-21 days
it’s MULTIPLYING.

The macrophage bursts

Question 10

Macrophages are doing a terrible job of controlling the TB so who do we call?

Answer 10

GHOSTBUSTERS!

but actually T and B cells

Question 11

What do T and B cells do to the TB?

Answer 11

form tubercles

Question 12

How are tubercules formed?

Answer 12

fibroblasts come and lay down collagen fibres to contain the disease, macrophage dies off and you get a fatty deposit inside

Question 13

Can you get rid of the tubercules?

Answer 13

no they stay for ever even if you no longer have the disease

Question 14

What are the things that can happen once you get tubercules?

Answer 14

50% people clear the infection
some have latent infection - (dormant)
some get the progressive disease

Question 15

How do we go from tubercle to infection?

Answer 15

Bacteria multiply in the macrophage - uncontrolled lysis releases them.

Question 16

Bacteria does what to destroy tissues?

Answer 16

release enzymes

Question 17

5 symptoms of TB

Answer 17

night sweats
cough
blood in sputum
weight loss
afternoon fever

Question 18

How to diagnose (4)

Answer 18

chest xray
tuberculin skin test
sputum test - culture takes weeks
DNA probe

Question 19

can you use a gram stain?

Answer 19

no

Question 20

Can we immunise against TB?

Answer 20

yes- BCG vaccine for high risk groups

Question 21

criteria for anti-TB drugs?

Answer 21

• intracellular activity
• combination therapy
• interaction with other anti-TB
• prolonged therapy (so min s/e and low tox)
• should treat distinct TB populations

Question 22

What are the 4 first line anti-TB drugs?

Answer 22

Rifampicin
Isoniazid
Pyrazinamide
Ethambutol

Question 23

is Rifamicin bacteriostatic or cidal?

Answer 23

Cidal

Question 24

is Rifampicin orally fully absorbed?

Answer 24

yes - but less with food

Question 25

s/e of rifampicin

Answer 25

liver damage hypersensitivity reduced activity of other drugs (e.g. COC) red colour in bodily fluids

Question 26

is isoniazid bacteriostatic or cidal?

Answer 26

cidal or static prodrug

Question 27

how does isoniazid work?

Answer 27

reduces synthesis of mycolic acid (cell wall)

Question 28

is isoniazid given orally

Answer 28

usually yes but parenteral also available

Question 29

isoniazid well distributed?

Answer 29

yes - especially in the CSF

Question 30

where is isoniazid cleared

Answer 30

met in the liver, excret in the kid

Question 31

s/e of isoniazid

Answer 31

liver damage hypersensitivity reduced activity of other drugs (e.g. COC) peripheral neuropathy

Question 32

is pyrazinamide bacteriostatic or cidal?

Answer 32

cidal (prodrug)

Question 33

how does pyrazinamide work?

Answer 33

reduces synthesis of mycolic acid/damages bacterial memebrane

Question 34

PK of pyrazinamide?

Answer 34

Oral well absorbed | met in the liver, excret in the kid

Question 35

s/e of pyrazinamide?

Answer 35

joint pain liver damage hypersensitivity

Question 36

Which is the only drug that can actually kill off dormant bacteria

Answer 36

pyrazinamide

Question 37

Is ethambutol static or cidal?

Answer 37

static

Question 38

how does ethambutol work?

Answer 38

increases permeability of the cell wall

Question 39

PK of ethambutol

Answer 39

orally well absorbed and 50% excreted unchanged into the urine

Question 40

s/e of ethambutol?

Answer 40

not for under 5s joint pain optic neuritis - reversible

Question 41

5 2nd line treatments

Answer 41

``` streptomycin capreomycin cycloserine ciprofloxacin azithromycin ```

Question 42

What is the treatment schedule for active TB?

Answer 42

Rif & Isoniazid (6-9 months) | Pyrazin (2 months) & Ethan

Question 43

What is the treatment schedule for latent TB?

Answer 43

Treat pt on immunosupressants | Rif (6months) or Rif & Isoniazid (3 months)

Question 44

why long drug therapy?

Answer 44

dificult for drugs to penetrate tuburcules rupture of legions causes renewed infection Anti TB drugs only bacteriocidal against growing organisms

Question 45

Where does resistance come from?

Answer 45

poorly manage TB care