Pcol Sem 2 Test 2 Tb

Front 1

how do calcefied legions develop

Back 1

from TB being latent first

Front 2

why are pt taking drugs for rheumotoid arthritis more suceptible for TB infections

Back 2

these drugs are anti-TNF alpha and TNF alpha plays a role in keeping the infection walled off therefore it may result in a disseminated disease

Front 3

when is extrapulmonary TB usually seen

Back 3

in those that are immunosuppressed

Front 4

what is persistence of TB

Back 4

ability of TB to survive in spite of host defense due to its ability to halt the maturation of phagosome

Front 5

what is latency of TB

Back 5

ability of TB to exist in host for years

Front 6

what is seen in latent TB

Back 6

positive skin test
calcified legions

Front 7

what is the mechanism by which TB persists

Back 7

TB will block the fusion of the phagosome and endosome and then also prevent the acidification of the late phagosome via ATPase and also prevent the phagosome from fusing w/ a lysosome all of which allow TB to survive and prevent the phagosome from maturing

Front 8

how does the immune response fight a TB infection

Back 8

Th1 cells secrete IFN gamma (typically not given as a treatment) which stimulates the macrophages to finally mature the phagosomes to kill the bug. IFN gamma also stimulates the macrophages to produce TNF alpha which stimulates granuloma formation to help control the spread of TB

Front 9

with a skin test how would the bump of a pt w/ HIV look compared to a immunocompetent pt

Back 9

the HIV pt would have a smaller bump

Front 10

what are some results that would indicate a TB infections

Back 10

more lymphocytes and monocytes instead of neutrophils

elevated WBC count

Front 11

how does the Elispot test work

Back 11

antibody mediated test

Front 12

Streptomycin is a what line drug

Back 12

2nd line

Front 13

what are the unique structural features of mycobacterium

Back 13

mycolic acid, arabinogalactan, lipoarabinose

Front 14

what are the first line drugs for treatment of TB

Back 14

isoniazid
ethambutol
rifamycins
pyrazinamide

Front 15

what are the properties of Isoniazid

Back 15

prodrug
activated via catalase peroxidase (KatG)

Front 16

what is the mechanism of action of Isoniazid

Back 16

inhibits mycolic acid synthesis by inhibiting the enzyme enoyl ACP reductase

Front 17

what gene encodes for enoyl ACP reductase

Back 17

inhA

Front 18

what is the ADME of Isoniazid

Back 18

accumulates in casseous pockets/granulomas of infection

Front 19

what are the mechanims of resistance to Isoniazid

Back 19

mutations in katG (which converts it to active drug)
mutations in nhA (which encodes enoly ACP reductase; the drug target)
mutation in kasA (participates in mycolic acid synthesis)
mutation in ndh

Front 20

what must be given a long w/ Isoniazid and why

Back 20

pyridoxine (vit B6)

it must be given b/c Isoniazid and its metabolites interfers w/ an enzyme reaction that requires pyridoxine therefore we give pyridoxine to compete w/ Isoniazid

Front 21

what are the adverse reactions of Isoniazid

Back 21

seizures/CNS effects due to the accumulation of glutamate due to insufficient pyridoxine (B6)

liver damage leading to non infections hepatitis therefore MUST MONITOR LIVER ENZYMES DURING TREATMENT

Front 22

what populations must be givent pyridoxine

Back 22

diabetics
HIV (immunocompromised)
pt on high lvl of isoniazid
alcoholics
pregnant women

Front 23

what are the Rifamycins

Back 23

rifampin
rifambutin
rifapentine

Front 24

what are the properties of rifamycines

Back 24

broad spectrum (gram +/-)
bactericidal

Front 25

what is the mechanism of action of Rifamycins

Back 25

binds to DNA dependent RNA polymerase (DDRP) and forms a complex preventing bacterial transcription

may bind to our mitochondrial DDRP at high concentrations

Front 26

what is the resistance to Rifamycins

Back 26

mutations in genes that encode bacterial DDRP

Front 27

what is the adverse effects of rifamycins

Back 27

may color body fluids, contact lenses w/ a red tint

induces CYPs including CYP3A4

hepatitis may occur (rare)

Front 28

what are the properties of Rifabutin and Rifapentin

Back 28

Rifabutin has less induction of CYPs so better for HIV patients

Rifapentin is intermediate b/t Rifampin and Rifabutin as far as CYP induction and has a longer t1/2 so greater distance b/t doses

Front 29

what are the properties of Ethambutol

Back 29

only works on Mycobacteria species

Front 30

what is the mechanism of action of ethambutol

Back 30

inhibits arabinosyl transferases that attach arabinosides to cell wall (INHIBITS CELL WALL SYNETHESIS)

Front 31

what gene encodes arabinosyl transferases

Back 31

embA

Front 32

what is the resistance to Ethambutol

Back 32

mutations in embA gene (encodes for arabinosyl transferase)

target overexpression/gene amplification resulting in a large amount of arabinosyl transferase allowing cell wall synthesis to occur even in the presence of ethambutol

Front 33

what is the adverse effect of ethambutol

Back 33

toxicity of optic nerve, neuritis resulting in changes in vision

Front 34

what are the properties of pyrazinimide

Back 34

prodrug
works on M tuberculosis species only
pyrazinoic acid is the active metabolite converted via pyrazinamidase

best activity of pyrazinoic acid in acidic environments like phagasomes

Front 35

what gene encodes pyrazinimidase

Back 35

pncA

Front 36

what is the resistance to pyrazinamides

Back 36

mutations in pncA gene therefore no active metabolites formed

Front 37

what is the MOA of pyrazinamides

Back 37

inhibits cell wall synthesis by inhibiting fatty acid synthase 1 (isoniazide inhibits fatty acid synthase 2) which is critical for mycolic acid synthesis

Front 38

what are the adverse effects of pyrazinamides

Back 38

hepatitis in those w/ liver/hepatic dysfunction therefore monitor liver enzymes

Front 39

what drugs can be used to treat latent TB

Back 39

isoniazide
rifamycins

Front 40

how long does it take someone to feel better when on 4 drug regimen

Back 40

1-2 weeks

Front 41

why does Tb antibiotic therapy take so long to work

Back 41

drug persists and becomes latent

Front 42

what is MDR

Back 42

Tb resistant to first line anti TB drugs (pyrazinamide, isoniazid, rifamycins, ethambutol)

Front 43

what is XDR

Back 43

resistant to MDR and 2nd line anti TB drugs (fluoroquinolones and at least one injectable antibiotic)

Front 44

what are the 2nd line drugs

Back 44

ethionamide
aminosalicylic acid
cycloserine
streptomycin
capreomycin
amikacin
fluoroquinolones
linezololid
interferon gamma

Front 45

what does capreomycin do

Back 45

inhibit protein synthesis

Front 46

what does streptomycin do

Back 46

aminoglycoside that inhibits protein synthesis

Front 47

what does cyclocerine do

Back 47

analog of alanine which is a component of peptidoglycan cell wall

interferes w/ cell wall synethesis

Front 48

what does aminosalicylic acid do

Back 48

analog of PABA therefore inhibits folate metabolism

Front 49

what does ethionamide do

Back 49

inhibit cell wall synthesis same target as isoniazide (enoyl ACP reductase)