TB Flashcards
1
Q
What type of bacterium is Mycobacterium tuberculosis?
A
Slow-growing, acid-fast, obligate aerobe with a lipid-rich cell wall.
2
Q
What makes M. tuberculosis resistant to many antibiotics?
A
Its lipid-rich cell wall containing mycolic acids.
3
Q
Why are multiple drugs used to treat TB?
A
To target both active and dormant bacteria and prevent resistance development.
4
Q
What are the first-line drugs for TB treatment?
A
Rifampin, Isoniazid, Pyrazinamide, and Ethambutol (RIPE).
5
Q
What is the mechanism of action of isoniazid?
A
Inhibits mycolic acid synthesis by targeting InhA after activation by KatG.
6
Q
How is isoniazid activated?
A
By the mycobacterial enzyme KatG.
7
Q
What is the major toxicity of isoniazid?
A
Hepatitis and peripheral neuropathy.
8
Q
How does isoniazid cause peripheral neuropathy?
A
By interfering with pyridoxine metabolism.
9
Q
What genetic factor affects isoniazid metabolism?
A
Acetylation rate determined by NAT2 (slow vs. fast acetylators).
10
Q
How does rifampin affect isoniazid toxicity?
A
Rifampin induces CYP2E1, increasing toxic metabolite formation.
11
Q
What activates pyrazinamide?
A
Conversion to pyrazinoic acid by pncA.
12
Q
How does pyrazinamide work?
A
Disrupts multiple processes including CoA synthesis via panD inhibition.
13
Q
At what pH is pyrazinamide active?
A
pH < 5.5.
14
Q
What is the major toxicity of pyrazinamide?
A
Hepatitis and arthralgia.
15
Q
How does resistance to pyrazinamide develop?
A
Primarily via mutations in pncA.
16
Q
What is the mechanism of action of ethambutol?
A
Inhibits arabinosyl transferase, affecting arabinogalactan synthesis.
17
Q
What is the major toxicity of ethambutol?
A
Optic neuritis (red-green color blindness).
18
Q
Why is ethambutol synergistic with rifampin?
A
It increases cell wall permeability.
19
Q
What is the mechanism of action of rifampin?
A
Binds RNA polymerase and blocks RNA chain elongation.
20
Q
What are key side effects of rifampin?
A
Orange body fluids, CYP enzyme induction, drug interactions.
21
Q
What is rifapentine and how is it different?
A
A rifampin derivative with longer half-life and more lipophilic.
22
Q
What is the mechanism of fluoroquinolones in TB?
A
Traps DNA gyrase on DNA, preventing supercoil resolution.
23
Q
Which fluoroquinolone is preferred for TB?
A
Moxifloxacin – better PK and lesion penetration.
24
Q
What is the mechanism of bedaquiline?
A
Inhibits ATP synthase.
25
What is bedaquiline used for?
MDR-TB and XDR-TB as part of the BPaL regimen.
26
What activates pretomanid?
Ddn enzyme in M. tb.
27
What is the mechanism of action of pretomanid?
Inhibits mycolic acid synthesis and generates reactive nitrogen species under anaerobic conditions.
28
What are second-line TB agents?
Streptomycin, ethionamide, PAS, cycloserine, capreomycin.
29
What is the MoA of cycloserine?
Inhibits cell wall synthesis by mimicking D-alanine.
30
What is the MoA of para-aminosalicylic acid?
Folate synthesis antagonist.
31
What is the MoA of ethionamide?
Chemically similar to isoniazid; inhibits mycolic acid synthesis.
32
What is the toxicity concern with second-line agents?
Higher toxicity and lower tolerability.
33
What is the standard treatment regimen for drug-susceptible TB?
2 months of RIPE (rifampin, isoniazid, pyrazinamide, ethambutol) followed by 4 months of isoniazid and rifampin.
34
What is the 'intensive phase' of TB treatment?
First 2 months using RIPE therapy to reduce bacterial load quickly.
35
What is the 'continuation phase' of TB treatment?
Next 4 months using isoniazid and rifampin to eliminate remaining bacteria.
36
How many total months is standard TB therapy?
6 months total (2 months intensive + 4 months continuation).
37
Why is adherence critical in TB treatment?
Non-adherence leads to treatment failure, relapse, and drug resistance.
38
What are risk factors for TB infection?
Close indoor contact with someone with active TB, living in a TB-endemic country.
39
What are risk factors for developing active TB disease?
HIV, immunosuppression, diabetes, children, and being <1 year from initial infection.
40
What does TST stand for in TB testing?
Tuberculin Skin Test.
41
What does IGRA stand for?
Interferon Gamma Release Assay.
42
What is the brand name of a common IGRA test?
QuantiFERON-TB Gold.
43
What does a positive TST or IGRA indicate?
Exposure to TB—suggests latent or active infection.
44
Can a TST or IGRA differentiate latent from active TB?
No, they only indicate TB exposure.
45
What is the class of isoniazid?
Mycolic acid synthesis inhibitor.
46
What is the mechanism of action of isoniazid?
Inhibits InhA enzyme to block mycolic acid synthesis.
47
How is isoniazid activated?
By bacterial catalase-peroxidase enzyme KatG.
48
How does resistance to isoniazid occur?
Mutation in KatG or InhA.
49
What is isoniazid's contribution to TB therapy?
Kills rapidly dividing extracellular mycobacteria.
50
What is the class of rifampin?
RNA synthesis inhibitor.
51
What is the mechanism of action of rifampin?
Inhibits bacterial RNA polymerase by binding the β subunit.
52
How does resistance to rifampin occur?
Mutations in the rpoB gene.
53
What is rifampin's role in TB treatment?
Active against slow-growing bacteria and prevents relapse.
54
What is the class of pyrazinamide?
Prodrug with multiple targets.
55
How is pyrazinamide activated?
Converted to pyrazinoic acid by bacterial pncA enzyme.
56
What is the mechanism of action of pyrazinamide?
Disrupts membrane energetics and CoA biosynthesis.
57
What is pyrazinamide active against?
Dormant mycobacteria in acidic environments.
58
How does resistance to pyrazinamide occur?
Mutations in the pncA gene.
59
What is the class of ethambutol?
Cell wall synthesis inhibitor.
60
What is the mechanism of action of ethambutol?
Inhibits arabinosyl transferase, affecting arabinogalactan synthesis.
61
What is ethambutol's role in TB therapy?
Enhances activity of other drugs and prevents resistance.
62
How does resistance to ethambutol occur?
Mutations in embB gene.
63
What is the class of moxifloxacin?
Fluoroquinolone.
64
What is the mechanism of action of moxifloxacin?
Inhibits DNA gyrase (topoisomerase II).
65
When is moxifloxacin used in TB?
MDR-TB or in patients intolerant to first-line agents.
66
What is the class of bedaquiline?
ATP synthase inhibitor.
67
What is the mechanism of action of bedaquiline?
Inhibits the proton pump of ATP synthase.
68
When is bedaquiline used?
In treatment of MDR/XDR-TB.
69
How does resistance to bedaquiline occur?
Mutation in atpE gene.
70
What is the class of pretomanid?
Nitroimidazole prodrug.
71
How is pretomanid activated?
By bacterial enzyme Ddn.
72
What is the mechanism of action of pretomanid?
Inhibits mycolic acid synthesis and generates NO under anaerobic conditions.
73
When is pretomanid used?
As part of the BPaL regimen for MDR/XDR-TB.
74
What is the name of the organism that causes tuberculosis?
Mycobacterium tuberculosis.
75
What does 'acid-fast bacteria' mean?
Bacteria that retain carbol fuchsin stain even when treated with acid-alcohol due to mycolic acid in the cell wall.
76
How is acid-fast staining used to diagnose TB?
Acid-fast bacilli seen under microscopy suggest TB infection, especially in sputum samples.
77
What makes the mycobacterial cell wall unique?
It contains mycolic acids and arabinogalactan, making it thick, waxy, and hydrophobic.
78
How does the mycobacterial cell wall differ from Gram-positive and Gram-negative bacteria?
It lacks an outer membrane like Gram-negatives and peptidoglycan is covered with a lipid-rich layer unlike Gram-positives.
79
How does the cell wall affect susceptibility to antibiotics?
It limits drug permeability, making TB intrinsically resistant to many antibiotics.
80
How is isoniazid activated?
By the bacterial enzyme KatG.
81
What is the mechanism of action of isoniazid?
Inhibits mycolic acid synthesis.
82
How does resistance to isoniazid occur?
Mutations in KatG or InhA.
83
What is isoniazid’s role in TB therapy?
Sterilizes rapidly growing extracellular bacteria.
84
What is the mechanism of action of rifampin?
Binds RNA polymerase and inhibits transcription.
85
How does resistance to rifampin develop?
Mutations in rpoB gene.
86
What is rifampin’s contribution to TB treatment?
Kills slowly metabolizing organisms.
87
What is the mechanism of action of ethambutol?
Inhibits arabinosyl transferase, affecting cell wall synthesis.
88
How does resistance to ethambutol develop?
Mutations in embB gene.
89
What is ethambutol’s role in TB therapy?
Prevents resistance to other drugs and helps with permeability.
90
How is pyrazinamide activated?
By conversion to pyrazinoic acid by pncA.
91
What is the mechanism of action of pyrazinamide?
Disrupts CoA synthesis and energy production.
92
How does resistance to pyrazinamide occur?
Mutations in pncA.
93
What is pyrazinamide’s contribution to TB therapy?
Kills dormant bacteria in acidic environments.
94
What is the mechanism of action of moxifloxacin?
Inhibits DNA gyrase.
95
How does resistance to moxifloxacin occur?
Mutations in gyrA and gyrB.
96
What is moxifloxacin’s role in TB therapy?
Used in MDR-TB and as a substitute for first-line agents.
97
What is the mechanism of action of bedaquiline?
Inhibits ATP synthase.
98
How does resistance to bedaquiline occur?
Mutations in atpE.
99
What is bedaquiline’s role in TB treatment?
Used in MDR/XDR-TB regimens like BPaL.
100
How is pretomanid activated?
By the enzyme Ddn in M. tuberculosis.
101
What is the mechanism of action of pretomanid?
Blocks mycolic acid synthesis and generates NO under anaerobic conditions.
102
What is pretomanid’s role in TB therapy?
Part of BPaL regimen for MDR/XDR TB.
103
Why are some drugs considered second-line TB agents?
Due to higher toxicity, lower efficacy, or resistance to first-line agents.
104
What are examples of second-line TB agents?
Streptomycin, ethionamide, PAS, cycloserine, capreomycin.
105
What is the name of the organism that causes tuberculosis?
Mycobacterium tuberculosis.
106
What does “acid-fast bacteria” mean?
Bacteria with waxy cell walls rich in mycolic acid that retain the carbol fuchsin stain even after acid-alcohol treatment.
107
How does acid-fast staining help diagnose active TB?
Acid-fast bacilli in stained sputum samples indicate an active mycobacterial infection like TB.
108
What is unique about the mycobacterial cell wall?
It contains peptidoglycan linked to arabinogalactan and a thick outer layer of mycolic acids, making it waxy and hydrophobic.
109
How does the mycobacterial cell wall differ from Gram-negative and Gram-positive bacteria?
It lacks the outer membrane of Gram-negatives and has a much thicker lipid-rich outer wall than Gram-positives.
110
How does the TB cell wall influence susceptibility to antibiotics?
It limits permeability, reducing antibiotic effectiveness and requiring specialized drugs.
111
How is isoniazid activated?
By the mycobacterial enzyme KatG.
112
What is the MOA of isoniazid?
Inhibits mycolic acid synthesis by targeting InhA.
113
How does resistance to isoniazid occur?
Mutations in katG or inhA.
114
What is isoniazid’s contribution to TB therapy?
Kills rapidly replicating extracellular mycobacteria.
115
What is the MOA of rifampin?
Binds the β-subunit of RNA polymerase and inhibits RNA synthesis.
116
How does resistance to rifampin develop?
Mutations in the rpoB gene.
117
What is rifampin’s role in TB treatment?
Kills semi-dormant bacteria and prevents resistance.
118
What is the MOA of ethambutol?
Inhibits arabinosyl transferase, disrupting arabinogalactan synthesis in the cell wall.
119
How does resistance to ethambutol occur?
Mutations in the embB gene.
120
What is ethambutol’s contribution to TB therapy?
Enhances cell wall permeability and prevents resistance development.
121
How is pyrazinamide activated?
Converted to pyrazinoic acid by pncA.
122
What is the MOA of pyrazinamide?
Disrupts membrane potential and CoA biosynthesis under acidic conditions.
123
How does resistance to pyrazinamide occur?
Mutations in pncA.
124
What is pyrazinamide’s role in TB therapy?
Kills dormant bacteria in acidic environments like within macrophages.
125
What is the MOA of moxifloxacin?
Inhibits DNA gyrase (topoisomerase II), interfering with DNA replication.
126
How does resistance to moxifloxacin occur?
Mutations in gyrA or gyrB.
127
What is moxifloxacin’s role in TB therapy?
Used as a second-line or substitute drug in MDR-TB.
128
What is the MOA of bedaquiline?
Inhibits the proton pump of ATP synthase, disrupting energy production.
129
How does resistance to bedaquiline occur?
Mutations in atpE gene.
130
What is bedaquiline’s role in TB treatment?
Key agent in MDR/XDR-TB regimens (e.g., BPaL).
131
How is pretomanid activated?
By the Ddn enzyme in M. tuberculosis.
132
What is the MOA of pretomanid?
Inhibits mycolic acid synthesis and releases nitric oxide under anaerobic conditions.
133
What is pretomanid’s role in TB treatment?
Used in the BPaL regimen for MDR/XDR-TB.
134
Why are some drugs considered second-line agents for TB?
Due to increased toxicity, lower efficacy, or use in resistant cases.
135
What are examples of second-line TB agents?
Streptomycin, cycloserine, ethionamide, PAS, capreomycin.
