Respiratory Bridges Drugs For Tuberculosis

Front 1

what organism causes tuberculosis?
How long is Tx generally?
How is preventative tx different from tx of active organism

Back 1

mycobacterium tuberculosis
6-24 months
preventative - single drug
active-combination

Front 2

List the 1st line drugs for tuberculosis

Back 2

RRIPEs
Rifabutin
Rifampin
Isoniazid
pyrazinamide
ethambutol
streptomycin

Front 3

why are mycobacteria hard to treat? 4

Back 3

1. grow slowly
2. infective material can reside in host cell
3. thick lipid-rich cell wall
4. can lay dormant - and be resistant or killed very slowly

Front 4

why must combination therapy be used in TB?

Back 4

Tb is known to create drug resistant strains - so we hit them double hard if a strain resistant to oen drug emerges

Front 5

what drugs do we use in asymptomatic or latent TB infection?

Back 5

isoniazid ALONE

alternative - rifampin

Front 6

what is 1st line tx for active TB infection

Back 6

Isoniazid and Rifampin

Front 7

MOA of isoniazid

bacteriocidal or bacteriostatic

Back 7

INH is a prodrug - and acive metabolite is formed by mycobacterial enzyme

inhibits synthesis of mycolic acid - which is a fatty acid in the cell wall

It is bacteriocidal!!!

Front 8

pharmacokinetics of isoniazid
cleared by?
excreted by?
what is distribution of isoniazid?

Back 8

cleared by liver - there is a bimodal distribution of clearance based on genetic polymorphism
Excreted in urine - mostly as metabolites - so renal dosing not required
WIDE distribution - including CSF and macrophages - penetrate caseous TB lesions

Front 9

what does isoniazid inhibit, as far as side effects
other side effects...

Back 9

Cyp3A4, among others -
can inhibit the metabolism of other drugs

inhibits neurons and HEPATOCYTES!!!! (most freq)
drug induced hepatits
peripheral neuropathy and CNS toxicity

Front 10

most important Side effect of isoniazid.
and most important risk factor for this side effect

Back 10

drug induced hepatitis
AGE
clinical hepatitis - loss of appetie, NV, jaundice may show a spike in ALT, which is ok, but >5x is bad - occurs in 20%
CONTINUE therapy if subclinical
discontinue if showing signs of hepatitis or ALT >5x ULN

Front 11

how is peripheral neuropathy and CNS toxicity caused in isoniazid?

how do we prevent

Back 11

causes vit b6 deficiency

more frequent in slow acetylators, malnourished, ALCOHLICs or DIABETICS

Give pyridoxine concurrently (pyridoxine=vit B6)

Front 12

when is rifampin used?

Back 12

prophylactic tx of Tb - Can be used alone

in tx of active Tb infection- NEVER used alone - combo thx

Front 13

MOA of rifampin?
distribution?
drug drug interactions?

Back 13

inhibit bacterial DNA dependent RNA polymerase
selective toxicity - doesnt bind well to human RNA pol
WIDE distribution - CSF and Macrphages
POTENT CYP 3A4 inducer!!!!!!!!

Front 14

when using rifampin and isoniazid, what are cross-interacting?
what happens

Back 14

CYP 3A4 inhibitor vs inducer

inducer predominates

Front 15

side effects of rifampin

Back 15

RASH, fever, NVD, abdomen pain
Hepatitis - Rare but increase risk with alcoholism, chronic liver dz and old age

Flu like syndrome
stuff turns RED!!! urine, tears, sweat

Front 16

4R's of rifampin

Back 16

RNA polymerase inhibitor
Red/orange fluids
Rev up CYP3A4
Rapid resistance if used alone!

Front 17

when do we use rifabutin?

how is it different than rifampin

Back 17

in HIV px's
less potent inducer of CYPs
MORE EXPENSIVE

Front 18

pyrazinamide MOA and what environment does it work best

Back 18

bacteriocidal agent
Unclear MOA
works best in acidic environment - active against mycobacteria residing in acidic phagosomes

Front 19

pyrazinamide - how do we treat with?

Back 19

never given alone!! another 1st line drug

Front 20

pyrazinamide side effects

Back 20

hepatotoxicity - MOST hepatotoxic of all 1st line drugs (must monitor liver function during use)

AND Hyperuricemia - contra in gout pxs

Front 21

what is the RIP pneumonic for?

Back 21

Rifampin, isoniazide and pyrazinamide all kill the liver

All three are CIDAL!!!!

Front 22

ethambutol MOA?

Back 22

Inhibits arabinosyl transferase - Inh cell wall biosynthesis!!

Bacteriostatic!! only 1st line drug

not as effective as other 1st line - helps with decreasing emergence of resistance

Front 23

ethambutol side effects?

Back 23

Optic neuritis!

hyperuricemia - by decreasing uric acid excretin

Front 24

which TB drugs cause hepatotoxicity?

Back 24

Rifampin
isoniazid
pyrizanimide

Front 25

which Tb drugs cause hyperuricemia

Back 25

pyrizanimide
ethambutol

Front 26

when in streptomycin used in TB?

Back 26

only reserved for more serious TB infections - life threatening

Front 27

MOA of streptomycin,
what class of drugs is it?
how is it administered?
distribution?

Back 27

-Protein synth inhibitor -
aminoglycoside class of ABX
-bacteriocidal
-Given IM only!
- limited dist - penetrates cells/CNS porrly, acts mainly against extracellular bacilli
BUT it does penetrate caseous tissue

Front 28

streptomycin side effects

Back 28

ototoxicity - vertigo/hearing loss (maybe permanent)
nephrotoxicity
toxicity is dose related

Front 29

Dose for general population with TB - without any risk factor for resistance

Back 29

Initial tx - INH+RIF+PYR+(ETB) for 2 months
continuation tx - INH + RIF for 4 months
total 6 months

Front 30

Dosing for HIV patient with TB - without any risk factor for resistance

Back 30

initial - INH+RFB+PYR+ETB for 2 months
continutation - INH + RFB for 7 months

Front 31

Dosing for general population with TB - with a INH resistant strain

Back 31

initial - RIF+PZA+ETB for 6 months
continuation - none

Front 32

dosing for HIV patient with TB - in a Rifampin resistant strain

Back 32

initial - INH+ETB+PZA+FQ(fluroquinolone) for 2 months
continue - INH+ETB+FQ for 10-16