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D&D Infectious Disease FINAL > Pharm - Tuberculosis Part 1 > Flashcards

Pharm - Tuberculosis Part 1 Flashcards

1
Q

true or false

tuberculosis is not caused by bacteria

A

FALSE

caused by mycobacterium tuberculosis bacteria

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2
Q

true or false

tuberculosis is contagious

A

true

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3
Q

true or false

tuberculosis is not a significant public health concern

A

FALSE - it is

global health concern affecting millions worldwide

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4
Q

name 3 types of infections that mycobacterium tuberculosis can cause

A

silent
latent
active

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5
Q

3 risk factors for tuberculosis infection

A

immunocompromised
poverty
crowding living conditions

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6
Q

TB is one of the top ___ causes of death worldwide

A

10

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7
Q

which 2 countries account for majority of tb cases

A

asia and africa

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8
Q

around how many people are infected with the TB bacterium

A

2 billion

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9
Q

does the mycobacterium tuberculosis bacterium go into our cells?

A

YES - it’s an intracellular pathogen. goes into the macrophages specifically

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10
Q

is mycobacterium tb aerobic or anaerobic?
motile or non motile?

A

aerobic non motile

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11
Q

does mycobacterium tb grow fast or slow

A

slowly replicates and lies dormant for a long time

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12
Q

how is mycobacterium tb able to be resistant to many antibiotics

A

it has a very thick hydrophobic (!60% LIPID) cell well that is rich in mycolic acids - hard for drug to get in

also, the antibiotic we design has to go into our body, then into our cells, and then into the bacteria to kill it - lot of steps bc it’s an intracellular pathogen

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13
Q

true or false

mycobacterium tuberculosis has a thicker cell wall than most bacteria

A

TRUE

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14
Q

mycobacterium TB has a ___- cell wall

A

waxy - from mycolic acids

~60% lipids

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15
Q

name the 4 layers of the cell wall of mycobacterium tuberculosis

what is the “mycomembrane?”

A

glycolipids (top)
mycolic acids
arabinogalactan
peptidoglycan (bottom)

4 LAYERS

“mycomembrane” is the glycolipids + mycolic acids

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16
Q

primary TB vs latent TB vs reactivation TB

A

primary TB = initial infection within the lungs

latent TB = ASYMPTOMATIC infection with no active disease

reactivation = return of active disease (often bc of some immunosuppression)

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17
Q

symptoms of pulmonary tb vs extrapulmonary tb

A

pulmonary tb symptoms - cough, chest pain, weight loss, fever

extrapulmonary - infection in other organs like lymph nodes bones and kidneys

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18
Q

true or false

mycobacterium tuberculosis can only infect the respiratory system

A

FALSE

can affect other tissues like lymph nodes, bone, kidneys, and even brain

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19
Q

4 diagnostic ways to test for TB

A

-tuberculin skin test

-IFNY release assay

-chest XRAY

-sputum culture

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20
Q

what does the tuberculin skin test measure

A

how the immune system of the patient will respond to tuberculosis proteins

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21
Q

issue with using chest x ray to diagnose TB

A

may get false positives of TB - just looking at pulmonary abnormalities and not any specific marker

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22
Q

5 first line drugs for tuberculosis

A

isoniazid
rifampin
pyrazinamide
ethambutol
streptomycin

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23
Q

what is DOT

A

directly observed therapy - done to ensure that the patient is being compliant with TB therapy

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24
Q

what is MDR-TB

A

multi-drug resistant TB

challenges to treat - needs specialized treatment

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25
Q

5 SECOND line drugs for TB

A

capreomycin
ethionamide
cycloserine
kanamycin
PAS (para-amino salicylate)

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26
Q

what is vDOT

A

VIDEO directly observed therapy for tb

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27
Q

when is the tb bacteria considered to be multi drug resistant in a patient

A

if it is resistant to 1st line drugs
(isoniazid, ethambutol, rifampin, streptomycin, pyrazinamide)

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28
Q

what is is XDR-TB

A

VERY resistant

TB that is resistant to at least rifampin and isoniazid
PLUS any quinoline
PLUS 1 of these 2nd lines: kanamycin, capreomycin, or amikacin

29
Q

explain the profile of patients that are more likely to develop XDR tuberculosis resistance

A

more likely to be younger

65 and older are actually less likely

30
Q

name 2 1st line TB agents that work by inhibiting cell wall synthesis and the specific layers they block the formation of

A

isoniazid and ethambutol

isoniazid - mycolic acid

ethambutol - arabinogalactan

31
Q

which 1st line TB agent inhibits RNA synthesis and how does it accomplish this

A

rifampin

inhibits DNA dependent RNA polymerase

if no RNA, can’t make protein

32
Q

give 2 MOAs of pyrazinamide

A

disrupts the plasma membrane

disrupts energy (ATP) synthesis

33
Q

what is the general size of isoniazid and what does this say about its function as an anti TB agent

A

SMALL MOLECULE

thus, able to penetrate the macrophages where the tb bacteria is located, and also easily absorbed

however, still kinda hard to get into the bacteria itself because of the waxy 4 layer cell wall

34
Q

is isoniazid bacteriostatic or cidal

A

CIDAL - for tb bacteria that are actively growing

35
Q

isoniazid is actually LESS effective for what kind of TB bacteria

A

atypical species

36
Q

is isoniazid usually used alone? why or why not

A

NO

usually used as combo therapy to reduce resistance to it

37
Q

true or false

isoniazid is a prodrug

A

TRUE

activated by KatG (mycobacterial catalase peroxidase) + coenzyme NADH into it’s active form

38
Q

isoniazid inhibits the synthesis of ________

A

mycolic acids

39
Q

what does isoniazid inhibit and how

A

inhibits the enzyme ACYL CARRIER PROTEIN REDUCTASE

does this by forming a complex with Acp and KasA

doing this inhibits the synthesis of the mycolic acid portion of the cell wall

40
Q

4 methods of isoniazid resistance

A

-bacteria can overexpress the enzyme (acyl carrier protein reductase - inhA)

-mutate or delete the katG gene that activates isoniazid into its active form

-mutate KasA (complex that forms with isoniazid)

-overexpress ahpC mutant (protects cell from oxidative stress)

41
Q

can isoniazid:

-be absorbed from GI tract?
-widely distribute in the tissues?
-penetrate the CNS?

A

yes to all

IT IS A SMALL MOLECULE

42
Q

Since isoniazid is absorbed from the GI tract, can we give it orally?

A

yes

43
Q

4 adverse effects of isoniazid*

A

drug-induced systemtic lupus erythematosus

hypersensitivity rxns

isoniazid-induced hepatitis

peripheral neuropathy

44
Q

as mentioned, an adverse effect of isoniazid is peripheral neuropathy

can anything be done to reduce the chance of this happening?

A

give with vitamin b6

45
Q

aside from helping to prevent peripheral neuropathy from isoniazid, why else is vitamin b6 good to administer with isoniazid

A

it can reduce the chance of SEIZURES

(seizures is a potential but rare AE of isoniazid bc it is able to cross BBB)

46
Q

explain the metabolism of isoniazid and is there any concern with it

A

phase 2 acetylation happens FIRST – to N-Acetyl INH

then it undergoes phase 1 hydrolysis – to ACETYLHYDRAZINE WHICH IS HEPATO TOXIC!!!

acetylhydrazine can acetylate macromolecules – hepatic proteins

47
Q

if isoniazid is administered alone, around how long is it until resistence emerges

what is the mechanism of resistance?

A

2-3 months

the drug can’t get into the organism (bacteria)

48
Q

rifampin is a semisynthetic derivative of ______

A

rifamycin

49
Q

is rifampin static or cidal and what is spectrum

A

broad spectrum - (+), (-), and enteric

bactericidal

also obviously active against mycobacterium tuberculosis

50
Q

explain the regimen in which isoniazid is given

A

ALWAYS given with isoniazid for cases of active TB

NOT GIVEN ALONE

51
Q

explain the MOA of rifampin

A

binds beta subunit (ALLOSTERIC SITE) of DNA dependent RNA polymerase to INHIBIT RNA SYNTHESIS (inhibit mRNA synthesis = no proteins and bacteria can’t survive)

52
Q

true or false

rifampin does not bind human RNA polymerase

A

TRUE - only bacterial

53
Q

explain the resistance mechanism for rifampin

A

point mutations occur in the RNA polymerase WHICH DECREASES RIFAMPIN BINDING TO IT

54
Q

what is the name of the enzyme that promotes transcription of DNA to mRNA

A

DNA-dependent RNA polymerase

(this is the enzyme that rifampin inhibits)

55
Q

is rifampin given orally?

A

yes - well absorbed

given as capsules

56
Q

true or false

rifampin is not well distributed

A

FALSE

readily distributed in tissues and phagocytic cells (including macrophages where mycobacterium infects!)

57
Q

significance of how rifampin is metabolized

A

metabolized by liver into bile, where it undergoes enterhepatic recirculation — this gives it a longer half life

58
Q

differentiate between the excretion of isoniazid vs rifampin

A

isoniazid - in urine

rifampin - mainly in feces as deactlyated metabolite

59
Q

**3 main AE of rifampin

A

turns urine/sweat/tears orange

nephrotoxicity - nephritis, acute tubular necrosis

cholestatic hepatitis

60
Q

**MAIN special consideration of rifampin

A

it is an inducer of CYP450 isoforms!!!

therefore, serum levels of many drugs will decrease bc their metabolism is increased

ie - oral contraceptives may not work

61
Q

name 6 classes of drugs that are metabolized by CYP system and thus will have a DDI with rifampin and their serum levels will decrease

A

methadone
oral contraceptives
anticoagulants
anticonvulsants
protease inhibitors
NNRTIs

62
Q

RIFAMPIN inhibits the synthesis of _____________

A

mRNA

63
Q

2 mechanisms rifampin resistance

A

mutations in rpoB gene (encodes B subunit of RNA polymerase)

ABC transporters such as Dac C (D-ala-D-ala-carboxypeptidase) can pump the drug out

64
Q

true or false

pyrazinamide is a first line agent for tb

A

true

65
Q

explain the MOA of pyrazinamide

A

diffuses into granuloma of mycobacterium tuberculosis

this is where pyrazinamidase (a tb enzyme) converts pyrazinamide into the ACTIVE FORM – PYRAZINOIC ACID

this pyrazinoic acid BLOCKS THE SYNTHESIS OF COENZYME A —- thus inhibiting ATP synthesis - less energy – inhibits trans-translation

in acidic conditions, acid gets protonated and disrupts cell membrane function to cause cell death

mechanism is not well established – BUT THOUGHT TO COLLAPSE MEMBRANE POTENTIAL AND AFFECT TRANSPORT FUNCTIONS OF THE MEMBRANE

66
Q

true or false

pryazinamide is a prodrug

A

TRUE

converted by pyrazinamidase into the active form - pyrazinoic acid

67
Q

true or false

pyrazinamide does not enter macrophages

A

FALSE

it does

68
Q

half life pyrazinamide

A

6 hours

69
Q
A

D&D Infectious Disease FINAL (21 decks)

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