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Year 2 Resp Exam 2 > anti-TB, Linger, CIS/DSA > Flashcards

anti-TB, Linger, CIS/DSA Flashcards

1
Q

most likely anti-TB first line to cause hepatotoxicity

A

pyrazinamide

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2
Q

MOA isoniazid INH

A

mycolic acid synthesis

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3
Q

most active drug for Tx TB

A

isoniazid

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4
Q

mech R isoniazid

A

mutations causing overexpression inhA
mutation deletion of katG gene (katG metabolizes drug and makes it acitve)
promoter mutations causing overexpression ahpC
mutations in kasA(kasA carrienr protein synthesis)

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5
Q

combination of drugs rec for active TB?

A

isoniazid, rifampin, pyrazinamide, ethambutol

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6
Q

when do you use streptomycin for Tx of TB

A

severe forms

because of adverse effects and only IV

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7
Q

MOA ethambutol

A

inhibit mycobacterial arabinosyl transferases which are endoed by the embCAB operon(essential in mycobacterial cell wall)

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8
Q

primary purpose of ethambutol in empirical Tx TB

A

if you were R to isoniazid, pyrazinamide or rifampin

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9
Q

mech of R for ethambutol

A

mutations causing overexpression emb gene

mutations with embB gene

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10
Q

adverse rxn ethambutol

A

retrobulbar neuritis, loss visual acuity and red-green color blindness

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11
Q

why is ehtambutol relatively contraindicated in young patients

A

visual acuity and red-green color discrimination

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12
Q

adverse effects of isoniazid

A

INH induced hepatitis (increased aminotransferases)
clinical hepatitis (depends on age and risk factors)
peripheral neuropathy (B6 deficiency because INH promotes excretion)
CNS toxicity
fever skin rashes, iatrogenic SLE

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13
Q

INH is contraindicated in what

A

people who develop INH induced hepatitis or have had any serious reaction to isoniazid

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14
Q

at what point do you need to stop isoniazid based on aminotrasnferase levels

A

5x maximal level

3x still okay–> monitor very closely

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15
Q

MOA rifampin

A

binds to beta subunit of bacterial DNA dependent RNA polymerase and inhibits RNA synthesis
bactericidal mycobacteria
active in vitro against gram + and - cocci, some enteric bacteria, mycobacteria and chlamydia

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16
Q

R to rifampin occurs how

A

point mutations in rpoB gene that encodes B subunit of RNA polymerase
no cross-resistance to other classes of antimicrobials but cross resistance to other rifamycin derivatives (rifabutin and rifapentine)

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17
Q

mech R pyrazinamide

A

impaired uptake
mutations on pncA that impair biotransformation
no cross R to other anti-TB agents

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18
Q

clinical uses pyrazinamide

A

first line agen in conjucntion with INH and rigampin in short term regimens
wither targets intra or extra cell organisms

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19
Q

adverse effects pyrazinamide

A

Hepatotoxicity (most of first line agents)
GI upset
hyperuricemia
most common cause of drug rash among first line agents

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20
Q

MOA pyrazinamide

A

taken up by macrophages where converted to pyrazinoic acid which is transported via efflux pump and may renter
exact MOA unknown
disrupts mycobacterial cell membrane synthesis and transport functions

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21
Q

What enzymes are involved with biotransformation of INH

A

N acetyltransferase NAT2
CYP450s
NAT2 again

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22
Q

which TBdrug is potent reducer of CYP450s

A

rifampin

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23
Q

clinical uses of isoniazid

A

approved for Tx active TB and latent TB
typically dosed daily sometimes 2x weekly with second anti TB agent
as monoTx, duration 9 mo

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24
Q

clinical uses rifampin

A 
mycobacterial infections
can be given alone for latent TB
meningococcal asymptomatic carrier
prophylaxis in contact of children with H influenza type b
staph carriage
serious staph infections
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25
Q

what can you take prophylactically after contact with child wiht H influenza type b

A

rifampin

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26
Q

adverse rxns rifampin

A

strong p450 inducer (extreme caution in HIB taking protease reverse transcriptase inhibitors)
harmless red urine, feces, saliva, sweat, CSF, tears, contact lenses
rashes, GI distrubances, thrombocytopenia, nephritis
hepatotoxicity can occur but less common
can cause flue like syndrome

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27
Q

what drugs have reduced effects if taken concurrently with rifampin

A

digoxin, propanolol, ketoconazole, metoprolol, verapamil, methadone, corticosteroids, oral contraceptives

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28
Q

what can occur if administer rifampin less tahn 2x/week

A

flue like syndrome: fever, chills, myalgias, anemia and thrombocytopenia

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29
Q

MOA streptomycin

A

irreversible inhibitor protein synthesis but exact mech for bactericidal activity is not known
binds S12 ribosome of 30s subunit
poorly penetrates cells (extracell tubercle bacilli)

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30
Q

R to streptomycin occurs how

A

mutations in rpsl gene encoding S12 or the rrs gene encoding 16S rRNA which alter ribosomal binding site

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31
Q

Which mycobacteria are susceptible to streptomycin

A

tuberculosis, MAC, kansasii

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32
Q

clinical uses streptomycin

A

used when injectable drug is needed (life threatening TB) or severe R
IM or IB dosing dialy for adults for several weeks follwed by few times a week for months

33
Q

adverse effects streptomycin

A

ototoxicity- vertigo and hearing loss **most common

nephrotoxicity (dose related)

34
Q

streptomycin relative contraindications

A

pregnancy from potential cause of deafness in newborn

35
Q

first line TB Tx

A 
ethambutol
isoniazid
pyrazinamide
rifampin
streptomycin
36
Q

least potent P450 inducer

A

rifabutin

37
Q

second line TB drugs

A 
amikacin
aminosalicylic acid
capremycin
cycloserine
ethionamide
FQ
knamycin
linezolid
rifabutin
rifapentine
38
Q

Tx fo leprosy

A

clofazimine and dapsone

39
Q

Tx for INH resistant TB

A

dialy rifampin alone for 4 mo (6mo in children)

40
Q

what 2 factors increase risk of Tx failure

A

cavitary disease at presentation and a + sputum culture taken at 2 mo

41
Q

if TB patient has both risk factors how long should the coninutation phase of Tx be

A

7 mo

42
Q

how long is Tx for TB osteomyelitis

A

6-9 mo

43
Q

how long is TB meningitis Tx for

A

9-12 mo

44
Q

what additional drug is added for TB pericarditis

A

corticosteroid for 1-2 mo

45
Q

what is beneficial about the addition of pyrazinamide to INH-rifampin Tx

A

reduces duration time of Tx to 6 mo without loss of efficacy

46
Q

When is rifabutin substituted for rifampin

A

intolerance or unacceptable drug interactions

47
Q

IF patient is R to INH what is Tx

A

rifampin, pyrazinamide and ethambutol for 6 mo

48
Q

patient R to INH and cannot take pyrazinamide what is Tx

A

rifampin and ehtabutol for 12 mo

49
Q

Tx for R to rifamycins

A

12 mo with INH, ethambutol and FQ

pyrazinamide initial 2 mo

50
Q

MDR TB and XDR TB are treated how

A

daily DOT therapy

51
Q

Tx for MDR TB

A

all active first line agents and FQ and one injectable drug

52
Q

how long is Tx for MDR TB

A

18-24 mo

53
Q

tx regimen for LTBI

A

daily isoniazid for 9 mo

54
Q

patient jsut Dx with TB and not on ART, but CD<50

plan?

A

immediately begin ART with antiTB drugs

even though inc the risk of immune reconstitution inflammatory syndrome

55
Q

how does TB change Tx of an TNF inhibitor

A

stop TNF inhibitor in active TB or latent

56
Q

patient DX with LTBI but is pregnant, what do you do

A

wait to Tx till 2-3 mo post delivery because risk hepatotoxicity

57
Q

when do you not delay Tx of LTBI in pregnant women

A

if HIV+ or recent infection TB

58
Q

Initial Tx for recent TB infection in pregnant woman

A

INH, rifampin, ehtambutol for 2 mo

INH and rifampin for 7 mo

59
Q

Agents to avoid for TB Tx in pregnancy

A

streptomycin: congenital deaness

Kanamycin, amikacin and capreomycin– assumed to share toxicity of streptomycin

60
Q

when do we use second line agents in TB

A

in case of R
in case of failure of clinical response to Therapy
in case of serious Tx-limiting advserse drug reactions

61
Q

What second line drugs are similar to INH

A

ethionamide

62
Q

which second line TB drug inhibits cell wall synthesis?

adverse effects?

A

cycloserine

can cause peripheral neuropathy and CNS dysfunction

63
Q

Which second line TB drug can cause crytalluria and GI upset and HS reactions that are severe

A 
aminosalicyclid acid (PAS)
folate synthesis antagonist
64
Q

Which second line TB drugs are similar to streptomycin?

MOA?

A

kanamycin and amikacin
AG antibiotics
protein synthesis inhibitors

65
Q

what is amikacin used for

A

the most resistant strains and aytpical mycobacteria

66
Q

rrs mutations is assoc with which TB drug

A

capreomycin

67
Q

R to FQ in TB occurs how

A

point mutations in gyrase A subunit

68
Q

DM patients should use caution with what second line TB drug

A

FQ, because can impair glucose control

69
Q

severe side effects with linezolid

A

bone marrow suppression and irreversible peripheral and optic neuropathy

70
Q

What strains if rifabutin used to Tx

A

M tb, MAC, M fortuitum

71
Q

which rifamycin is preferered in HIV patients

A

rifabutin

72
Q

When is rifapentine indicated

A

rifampin-susceptible TB during continuation phase only

73
Q

What drug combination is used in Tx leprosy

A

dapsone rifampin and clofazimine

74
Q

what adverse effects are common with dapson

A

hemolysis and methemoglobinemia

75
Q

MOA dapson

A

inhibit folate synthesis

76
Q

What is used to prevent and Tx pneumocystitis jiroveci pneumonia

A

dapsone

77
Q

when is clofazimine indicated

A

sulfone-R leprosy or when patienets intolerant to sulfones

78
Q

adverse effects clofazimne

A

skin discoloration ranging from red-brown to black

GI intolerance occasionally

Year 2 Resp Exam 2 (33 decks)

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