Pharm - tuberculosis part 2

Question 1

SE pyrazinamide

Answer 1

not really specific - malaise, fever, etc

Question 2

spectrum of pyrazinamide

Answer 2

ONLY used for TB

Question 3

in what conditions is pyrazinamide most effective

Answer 3

ACIDIC CONDITIONS

Question 4

explain the tb regimen in which pyrazinamide is administered

Answer 4

either with isoniazid + rifampin or isoniazid + rifampin + ethambutol

ALWAYS at least with both isoniazid and rifampin

Question 5

does pyrazinamide get into cells?

Answer 5

yes - it has to to be active against TB.

it’s a small molecule - can penetrate macrophages and lysosomes by passive diffusion

Question 6

pyrazinamide is preferentially active against what kind of bacilli?

Answer 6

NON REPLICATING

Question 7

Pyrazinamide targets ________, which is important for the synthesis of acetyl CoA

Answer 7

aspartate decarboxylase

Question 8

2 resistance mechanisms against pyrazinamide

Answer 8

-decreased uptake into cells

-mutations that inhibit the conversion of the prodrug into the active form - pyrazinoic acid

Question 9

does pyriazinamide have cross resistance with other tuberculosis agents?

why or why not

Answer 9

NO

has a very unique MOA

Question 10

*****important AE of pyrazinamide

Answer 10

hyperuricemia, which can develop into acute gouty arthritis

this is bc pyrazinamide and uric acid compete for the same transporter, and thus the secretion of uric acid from the body is decreased

Question 11

is pyrazinamide well absorbed? well distributed? can it penetrate BBB?

Answer 11

yes to all

only penetrates CNS when meninges are inflamed tho

Question 12

1-5% of patients on pyrazinamide experience

Answer 12

hepatotoxicity

Question 13

MOA ethambutol

Answer 13

inhibits the synthesis of arabinogalactan - an important component of the m. tb cell wall

does so by competitively inhibiting arabinosyl transferase

Question 14

3 main AE ethambutol*

Answer 14

hyperuricemia
joint pain
optic neuritis (reversible if we discontinue the drug or lower the dose)

Question 15

2 1st line TB agents that can cause hyperuricemia

Answer 15

pyrazinamide
ethambutol

Question 16

what enzyme does ethambutol inhibit

Answer 16

arabinosyl transferase

leads to diruption of arabinogalactan synthesis, and thus increased permeability of the cell wall

Question 17

spectrum ethambutol

Answer 17

m. tuberculosis and other mycobacterial organisms

Question 18

regimen in which ethambutol is given

Answer 18

in combo therapy - w 2 or 3 other 1st lines

Question 19

arabinosyl transferase is encoded by the ______ operon

explain this operon

Answer 19

embCAB operon

EmbA and EmbB are involved in arabinogalactan synthesis

EmbC involved in lipoarabinomannan synthesis (LAM)

Question 20

2 resistance mechanisms for ethambutol

Answer 20

-overproduction of arabinosyl transferase (emb gene products)

-mutate EmbB gene structure mutants – drug may not be able to bind enzyme

Question 21

very important pharmacokinetic situation for ethambutol

Answer 21

it can accumulate in renal failure patients - need to reduce the dose for them

Question 22

can ethambutol be adminstered orally?

Answer 22

YES

well absorbed from GI

Question 23

**very important AE ethambutol

Answer 23

AFFECTS THE EYES:

-retrobulbar neuritis – loss of vision and develop red-green color blindness

Question 24

streptomycin AE

is it 1st line?
do we really use anymore?

Answer 24

it is 1st line but we don;t really use - very toxic and can cause permanent hearing loss

Question 25

kanamycin is _____ line for tuberculosis

Answer 25

SECOND LINE

Question 26

adverse effects kanamycin

Answer 26

hearing loss
kidney damage
contraindicated in pregnancy

Question 27

how is tb diagnosed

Answer 27

THREE THINGS

-chest x ray
-sputum sample
-skin or blood test

Question 28

how is tb treated

Answer 28

with antibiotics

Question 29

3 symptoms of active tb

Answer 29

weight loss
loss of appetite
night sweats

Question 30

how is TB transmittied

Answer 30

ONLY through the air - nothing else

Question 31

what does isoniazid inhibit in mycobacterium tuberculosis

Answer 31

mycolic acids

Question 32

common side effect isoniazid

Answer 32

hepatotoxicity

Question 33

what enzyme in the liver metabolizes isoniazid

Answer 33

NAT2 (n-acetyl transferase)

Question 34

true or false

rifampin causes increased plasma levels of drugs metabolized by the CYP system

Answer 34

FALSE

decreases their serum levels by increasing CYP activity

Question 35

true or false

rifampin is a potent inducer of the CYP system

Answer 35

TRUE