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49 Cards in this Set

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  • Back
how do calcefied legions develop
from TB being latent first
why are pt taking drugs for rheumotoid arthritis more suceptible for TB infections
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
when is extrapulmonary TB usually seen
in those that are immunosuppressed
what is persistence of TB
ability of TB to survive in spite of host defense due to its ability to halt the maturation of phagosome
what is latency of TB
ability of TB to exist in host for years
what is seen in latent TB
positive skin test
calcified legions
what is the mechanism by which TB persists
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
how does the immune response fight a TB infection
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
with a skin test how would the bump of a pt w/ HIV look compared to a immunocompetent pt
the HIV pt would have a smaller bump
what are some results that would indicate a TB infections
more lymphocytes and monocytes instead of neutrophils

elevated WBC count
how does the Elispot test work
antibody mediated test
Streptomycin is a what line drug
2nd line
what are the unique structural features of mycobacterium
mycolic acid, arabinogalactan, lipoarabinose
what are the first line drugs for treatment of TB
isoniazid
ethambutol
rifamycins
pyrazinamide
what are the properties of Isoniazid
prodrug
activated via catalase peroxidase (KatG)
what is the mechanism of action of Isoniazid
inhibits mycolic acid synthesis by inhibiting the enzyme enoyl ACP reductase
what gene encodes for enoyl ACP reductase
inhA
what is the ADME of Isoniazid
accumulates in casseous pockets/granulomas of infection
what are the mechanims of resistance to Isoniazid
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
what must be given a long w/ Isoniazid and why
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
what are the adverse reactions of Isoniazid
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
what populations must be givent pyridoxine
diabetics
HIV (immunocompromised)
pt on high lvl of isoniazid
alcoholics
pregnant women
what are the Rifamycins
rifampin
rifambutin
rifapentine
what are the properties of rifamycines
broad spectrum (gram +/-)
bactericidal
what is the mechanism of action of Rifamycins
binds to DNA dependent RNA polymerase (DDRP) and forms a complex preventing bacterial transcription

may bind to our mitochondrial DDRP at high concentrations
what is the resistance to Rifamycins
mutations in genes that encode bacterial DDRP
what is the adverse effects of rifamycins
may color body fluids, contact lenses w/ a red tint

induces CYPs including CYP3A4

hepatitis may occur (rare)
what are the properties of Rifabutin and Rifapentin
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
what are the properties of Ethambutol
only works on Mycobacteria species
what is the mechanism of action of ethambutol
inhibits arabinosyl transferases that attach arabinosides to cell wall (INHIBITS CELL WALL SYNETHESIS)
what gene encodes arabinosyl transferases
embA
what is the resistance to Ethambutol
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
what is the adverse effect of ethambutol
toxicity of optic nerve, neuritis resulting in changes in vision
what are the properties of pyrazinimide
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
what gene encodes pyrazinimidase
pncA
what is the resistance to pyrazinamides
mutations in pncA gene therefore no active metabolites formed
what is the MOA of pyrazinamides
inhibits cell wall synthesis by inhibiting fatty acid synthase 1 (isoniazide inhibits fatty acid synthase 2) which is critical for mycolic acid synthesis
what are the adverse effects of pyrazinamides
hepatitis in those w/ liver/hepatic dysfunction therefore monitor liver enzymes
what drugs can be used to treat latent TB
isoniazide
rifamycins
how long does it take someone to feel better when on 4 drug regimen
1-2 weeks
why does Tb antibiotic therapy take so long to work
drug persists and becomes latent
what is MDR
Tb resistant to first line anti TB drugs (pyrazinamide, isoniazid, rifamycins, ethambutol)
what is XDR
resistant to MDR and 2nd line anti TB drugs (fluoroquinolones and at least one injectable antibiotic)
what are the 2nd line drugs
ethionamide
aminosalicylic acid
cycloserine
streptomycin
capreomycin
amikacin
fluoroquinolones
linezololid
interferon gamma
what does capreomycin do
inhibit protein synthesis
what does streptomycin do
aminoglycoside that inhibits protein synthesis
what does cyclocerine do
analog of alanine which is a component of peptidoglycan cell wall

interferes w/ cell wall synethesis
what does aminosalicylic acid do
analog of PABA therefore inhibits folate metabolism
what does ethionamide do
inhibit cell wall synthesis same target as isoniazide (enoyl ACP reductase)