Exam 4 - Tuberculosis Flashcards Preview

Therapeutics V Spring 2019 (P3 Spring) > Exam 4 - Tuberculosis > Flashcards

Flashcards in Exam 4 - Tuberculosis Deck (81):
1

what bug causes tuberculosis?

mycobacterium tuberculosis

2

gram stain of mycobacterium tuberculosis?

Aerobic
non-spore forming
bacillus

3

what are factors associated with MDR-TB?

inadequate therapy (monotherapy or suboptimal dose)
Cavitary lesions

4

what drug combo is most commonly used for active TB treatment?

RIPPE
Rifampin, Isoniazid, Pyrazindamide, Pyridoxine (B6), Ethambutol

5

Mycobacterium tuberculosis:
_____ rich cell wall that contains _______ and is _______ to many durgs

Lipid rich
contains mycolic acid
impermeable to many drugs

6

Transmission of Tb:
Only _____ Tb infections can be transmitted

active

7

Transmission of Tb:
spread by __________

aerosol droplets (speaking, coughing, spitting)

8

what are the extrapulmonary tuberculosis things that can happen?

genitourethral tuberculosis
TB w/ arthritis or osteomyelitis
TB menigitis

9

Issues with HIV and diagnosis of TB?

HIV patients have weak immune systems ---- they wont have a positive response to skin testing as easily (high false negative rate)

10

Clinical presentation for TB in healthy patients?

Fever/chills
NIGHT SWEATS
anorexia
wt loss
cough
hemoptysis/SOB
malaise

11

Clinical presentation of TB in HIV patients?

if early HIV --- kinda similar... extrapulmonary at higher risk
if late HIV --- v high extrapulmonary disease risk

12

2 main ways to screen for TB?

PPD (purified protein derivative)
IGRAs (interferon gamma release assays)

13

when to do IGRA over PPD for diagnosis?

when pts have rcvd BCG vaccinated

14

T or F: only need to do drug susceptibility for TB when i HIV pts?

false --- do it for every isolate!!

15

Someone is deemed noninfectious when receiving effective therapy, improving clinically, and ??

pt has negative sputum smear results for 3 CONSECUTIVE days (each sputum collected on a different day)

16

what are the 2 phases for TB treatment?

intensive phase then continuation phase

17

If pts have HIV and you want to treat TB....
-If pts have CD4 < 50 cells/uL start ART within ______ of TB therapy
-If pts have CD4 >/= 50 cells/uL start ART within ______ of TB therapy

< 50: within 2 weeks

> 50: delay ART until 8 - 12 weeks

18

Rifampin is a hella _______ of CYP

inducer

19

_________ is the most active FQ against M. tuberculosis

Moxifloxacin

20

For MDR-TB:
Treat any patient with ______ resistant TB (or if _____ resistance is absent or unknown with a MDR-TB regimen

rifampin resistant; INH resistance unknown

21

For MDR-TB:
Must include what 3 drugs for sure for treatment?

A FQ (Levo or moxi)
+
Bedaquiline
+
Linezolid

22

Treatment options for latent TB infection?

Rifampin QD x 4 mos
**INH + Rifapentine once weekly x 12 weeks**
INH daily x 6 - 9 mos

23

INH: how metabolized?

by liver --- N-acetyltransferase

24

INH: into CSF?

yas -- super well

25

INH: good or bad oral bioavail?

good

26

ADEs of INH?

Hepatitis
Neurotoxic = PERIPHERAL NEUROPATHY --- give Vit. B6

27

Dose adjustments for INH?

when severe hepatic insufficiency or renal failure

28

why supplement B6 with INH therapy?

INH increases pyridoxine excretion --- need it to prevent peripheral neuropathy

29

INH: inducer or inhibitor of P450?

inhibitor

30

ADEs of rifampin?

Hepatoxicity
discolored urine (sweat and tears)/(orange color) -- can permanently stain contact lenses

31

ADEs of Pyrazinamide?

Hepatoxicity
Hyperuricemia
Joint pain - arthralgias (MCMP notes)

32

ADEs of Ethambutol?

Peripheral neuropathy
Optic neuritis (can be irreversible if not discontinued)

33

ADEs of streptomycin?

otoxicity
nephrotoxicty
(it is a aminoglycoside!!)

34

Do you renal dose adjust for Pyrazinamide or Ethambutol?

Ethambutol

35

ADE with PAS (P-aminosalicylic acid)

GI!! -take with meals

36

ADEs of Cycloserine?

"PSYCHO-serine"
depression/personality changes/psychosis/seizures

37

INH has to be activated by the ______ protein

KatG (comes M.tb)

38

INH forms adducts with _______ and ______

NAD+ and NADP+

39

what enzymes are inhibited by the INH/NAD+/NADP+?

InhA and KasA (inhibits mycolic acid synthesis)
DHFR (dihydrofolate reductase)

40

Activated INH inhibits _______ which is a component of ________ synthase

inhibits: InhA
FAS II (fatty acid synthase)

(overall affects arabino-galactan -- part of mycobacterium

41

Overall INH leads to a ________ (why it is good at killing Tb)

leads to defective cell wall

42

INH resistance happens via what?

by over expression of InhA
and somehow activation of INH by KatG is stopped (Tb probs stops making Katg)

43

INH is metabolized how?

acetylated by N-acetyltransferase

44

INH Toxicity Mechanism:
Acetylisoniazed can become _________ (which I think is a toxic metabolite...)

acetylhydrazine

45

INH Toxicity Mechanism:
_______ converts to hepatotoxic metabolites

CYP2E1

46

INH Toxicity Mechanism:
_____ can acetylate acetylhydrazine to nontoxic diacetyhdrazine

NAT2

47

what does AFB stand for

acid fast bacteria

48

what does it mean to be AFB?

the bug stains SUPER well and cannot be decolorized

49

Pathology of Tb:
1. bacteria phagocytosed by alveolar macrophages in the lung/ cause proinflammatory response
2. Recruited cells (such as _______ cells) will form a _______

recruited cells = mononuclear cells
form a granuloma (tubercle)

50

Pathology of Tb:
3. Granuloma forms a _________ with fewer ________ in later stages
4. When immune status change containment fails
5. The granuloma ________ and spills viable/infectious bacilli into airways

forms a fibrous sheath; fewer penetrating blood vessels in later stages
granuloma caseates/decays/ruptures

51

Always a 10% lifetime risk of developing active infection when pt has latent Tb

but what things increase risk of activation of Tb?

Diabetes
HIV
Old age
malnutrition

52

INH Toxicity Mechanism:
(fast or slow) acetylators will lead to toxic metabolites
(fast or slow) acetylators will remove acetylhydrazine

slow = toxic
fast = removes the toxic metab

53

INH Toxicity Mechanism:
Induction of CYP________ leads to toxic metabolites

CYP2E1

54

INH Toxicity Mechanism:
_______ induces CYP2E1 and potentiates INH hepatotoxicity

rifampin

55

MCMP reason why we need to supplement B6 with INH therapy?

INH inhibits metabolism of pyridoxine to pyridoxal phosphate....

56

How is Pyrazinamid activated?

by pncA which is a nicotinamidase from M.Tb
(gets converted to pyrazinoic acid)

57

Pyrazinamide (PZA) is structurally similar to ________

nictinamide

58

Pyrazinamide (PZA):
facts about it being active in relation to pH?

NOT active at neutral pH/
WILL BE active if pH < 5.5

59

3 ideas of how Pyrazindamide works?

-inhibition of trans-translation
-inhibition of aspartate decarboxylase PanD
-Acidification of cytoplasm followed by disruption of energy metabolism

60

Pyrazinamide MOA Guess: Trans-Translation:
It gets converted to pyrazinoic acid and will bind and inhibit ______________

ribosomal protein S1 (RpsA) = proteins won't fold correctly

61

PZA = ?
POA = ?

PZA = pyrazinamide
POA = Pyrazinoic Acid

62

Pyrazinamide MOA Guess: inhibit PanD
panD normally converts ________ to ______

L-aspartate to alanine

63

Pyrazinamide MOA Guess: inhibit PanD
(PZA or POA) binds to PanD

POA (the activated form) does bind

(wont bind to mutant panD tho = resistance)

64

Pyrazinamide MOA Guess: inhibit PanD
overall will reduce the accumulation of ________ after the panD step

which will increase levels of _______

coA precursors;

free fatty acids

65

MOA of Ethambutol:
Inhibits __________ (which is involved in _________)

this causes a build up of ________

mycobacterial arabinosyl transferases;
polymerization of arabinogalactan;

build up of arabinan

66

Ethambutol:
is synergistic with _______

rifampin (increases penetration into cell)

67

Resistance to Ethambutol happens how?

over expression of or mutations of arabinosyl transferase

68

INH:
active against latent, growing or both forms of Tb?

JUST growing forms

69

Rifampin:
active against latent, growing or both forms of Tb?

both!!

70

Rifampin is most effective when the cell is _______

dividing

71

MOA of Rifampin:
Binds to ________ deep within the ________

to RNA pol
within DNA/RNA channel

72

Bacteriocidal or Bacteriostatic?
Rifampin?
Ethambutol?

Rifampin:cidal
Ethambutol: static

73

Rifapentine:
is a derivative of rifampin
it is more _______ and has a ______ half life

lipophilic
longer 1/2 life

74

Which aminoglycoside can be used for Tb?

Streptomycin (idk if others cant but they talk about streptomycin...)

75

Streptomycin and Tb:
most active against ______ forms

extracellular

76

Streptomycin and Tb:
used mainly when severe tuberculosis (ex: _______ or _______0

meningitis or disseminated

77

Bedaquiline:
Given PO or IV?
cidal or static?
active against latent, growing or both forms of Tb?

PO
cidal
both!

78

Bedaquiline MOA?

inhibits ATP synthase

79

what are some 2nd line agents fro Tb?

FQs
Ethionamide
para-aminosalicylic acid
Cycloserine
Carpreomycin

80

when to consider 2nd line agents for Tb?

if resistant to 1st line...
failure of clinical response to first line agents
intolerance of first line
have expert guidance available to deal with toxic side effects

81

why are the 2nd line agents for Tb used as 2nd line?

less well tolerated/greater incidence of side effects.....(SHOCKING)