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Antimycotic agents Flashcards

1
Q

What is the different protein that makes up part of the cell wall in mycobacteria?

A

Mycolic acid

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2
Q

What is the classic culture result for mycobacterium?

A

Acid-fast

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3
Q

What does mycobacterium avium complex cause?

A

Pulmonary and disseminated infections

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4
Q

What does mycobacterium lepra cause?

A

leprosy

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5
Q

What is mycolic acid?

A

Lipid in the cell wall of TB

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6
Q

What is the gram stain of mycobacterium? Why?

A

gram stain poorly or not at all due to mycolic acid structure

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7
Q

Where does TB like to replicate?

A

macrophages

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8
Q

How fast does TB grow?

A

Slowly

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9
Q

What is the morphology of TB?

A

Rod

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10
Q

What infection is closely correlated with TB infection?

A

HIV

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11
Q

How is TB transmitted?

A

Respiratory droplets

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12
Q

True or false: most patient infected with TB show some type of symptoms

A

false-90% are asymptomatic

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13
Q

What are the classic symptoms for TB infection?

A

Night sweats
Weight loss
Hemoptysis
Fever/chills

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14
Q

In latent TB infection, what are the ssx? CXR results? Sputum smears/cultures? Are they infectious?

A

Nothing will show positive, except for blood tests (IFN-gamma release)

They are not infectious

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15
Q

What are the diagnostic criteria for active TB?

A

Positive blood tests
CXR abnormal
sputum

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16
Q

What is the IFN-gamma test for TB?

A

Expose WBCs of a pt to TB antigen, and see if they produce IFN-gamma. If they do, then positive for infection

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17
Q

What are the obstacles of treating TB?

A

Slow growing
Toxicity of TB drugs
Resistance

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18
Q

Why are patient not compliant with TB drugs?

A

Really toxic

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19
Q

Why do you always treat TB with 3-4 different drugs?

A

Resistance

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20
Q

What is the MOA of rifamycin? Is it bactericidal or bacteriostatic? Why is this drug particularly useful for treating TB?

A

Inhibits RNA synthesis by targeting bacterial RNA polymerase
Bactericidal
Goes into macrophages

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21
Q

What is the MOA of streptomycin?

A

Inhibits protein synthesis by targeting the 30s subunit

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22
Q

What is the MOA of isoniazid? Is this bactericidal or bacteriostatic? Why is this drug particularly useful for treating TB?

A

Inhibit mycolic acid synthesis by forming covalent bond with two proteins
Bactericidal
Can go into macrophages

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23
Q

What is the MOA of Ethambutol?

A

Inhibit arabinosyl which inhibits cell wall synthesis

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24
Q

What is the MOA of pyrazinamide? This is a synthetic analog to what compound?

A

Inhibits cell membrane synthesis (somehow?)

Synthetic analog to nicotinamide

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25
What are the bacteria that are a part of the mycobacterium avium complex?
M. Avium | M. intracellulare
26
What are the ssx of MAC infection? In whom does each type of infection occur?
Pulmonary disease in immunocompetent individuals and disseminated disease in AIDS pts
27
How are the MAC bacteria acquired?
ingestion of contaminated food and water
28
What is the preferred regimen for active TB infection? (4 drugs, how long?)
Daily INH, Rifampin, pyrazinamide, and ethionamide x8 weeks
29
What is involved in the continuation phase of TB infection?
Daily INH and rifampin x18 weeks
30
What is the treatment for latent TB? What is the alternative
Isoniazid x9 months | Rifampin is alternative
31
Is isoniazid useful for MAC?
less effective than for TB
32
What vitamin supplement should pts on isoniazid treatment be placed on? Why?
B6 since isoniazid resembles B6, and will inhibit heme synthesis pathway at AIP synthase
33
Isoniazid is a prodrug. What converts it to the active form?
Mycobacterial catalase-peroxidase enzyme (Kat G)
34
True or false: INH is one of the safest and most effective TB treatment we have
True
35
What are the two ways in which TB develops resistance to INH?
Mutation in the Kat G gene | Overexpression of the inh A protein
36
Why is a combination drug therapy used in the treatment of TB?
Reduce resistance
37
Who has more toxic side effects with INH? What are the two chief toxicities associated with INH? Does this affect the efficacy of the drug?
Slow acetylators Peripheral neuropathy and hepatitis Does not affect efficacy
38
True or false: INH, Rifampin, Ethambutol, and pyrazinamide are all readily absorbed from the GI tract
True
39
What are the two factors that increase the probability that hepatitis will occur with INH treatment?
Age | EtOH dependence
40
What is the MOA of INH causing peripheral neuropathy?
B6 inhibition
41
In whom is peripheral neuropathy more likely?
Immunosuppressed | Slow Acetylators
42
What is are the side effects of rifampin?
n/v HA, dizziness Hepatitis
43
What is the benign side effect of rifampin that pts will worry about?
red-orange color of urine, feces, sweat, tears, and salive
44
What is the major concern for rifampin, and why should AIDS patients not take it? What is the alternative for them (hint: not INH)?
induces p450 enzymes, which will interfere with HIV drugs Rifabutin
45
True or false: pyrazinamide is an alternative drug for INH or rifampin
False-always used in combination with one of these
46
Pyrazinamide is administered as a prodrug. What activates it?
pyrazinamide enzyme of bacteria and low pH of macrophage lysosome
47
Why is the fact that pyrazinamide needs a low pH useful for therapy?
Good at killing macrophage engulfed TB
48
How does resistance to pyrazinamide develop?
Mutation in the pyrazinamide enzyme
49
What are the two major adverse effects of pyrazinamide? Which is seen in a small percent of pts, and which is seen in nearly all patients?
Hepatotoxic (5% of pts) | Hyperuricemia (nearly all)
50
Do you ever use pyrazinamide or ethambutol alone? Why or why not?
Nope | resistance
51
Is ethambutol useful for MAC?
Yep
52
How is resistance to ethambutol brought about?
Point mutations in the genes encoding arabinosyl transferase
53
What are the two major adverse effects of ethambutol?
``` Retrobulbar neuritis (color blindness) Hyperuricemia ```
54
When is streptomycin used for TB treatment?
Strains that are resistant to other first-line drugs
55
What is the major issue with streptomycin as compared to other TB treatments?
Does not penetrate into macrophages
56
What are the two major side effects with streptomycin?
Ototoxic | Nephrotoxic
57
What is the MOA of Rifabutin?
inhibits bacterial RNA polymerase (just like Rifampin)
58
True or false: Rifabutin has lesser activity against MAC organisms than Rifampin
False--much greater activity
59
When is Rifabutin used instead of Rifampin? Why?
In HIV pts to prevent the induction of p450 enzymes that may interfere with the antiretrovirals
60
What are the three drugs that are used for a MAC infection
1. macrolide 2. Rifampin 3. Ethambutol
61
When do you start to prophylax HIV pts for MAC? What drug(s) do you use?
CD4
62
What are the two forms of Mycobacterium leprae infection? What is the cellular response in each?
1. Lepromatous form (Th2 response) | 2. Tuberculoid form (Th1 response--they chose wisely)
63
What are the ssx of the tuberculoid form of M. Leprae infection?
hypopigmented plaque or macules
64
What are the ssx of the lepromatous form of M. Leprae infection?
Modules and disfiguring skin lesions that develop very slowly
65
A biopsy of a lesion of the tuberculoid form of M. Leprae infection will show what? Lepromatous form?
``` Tuberculoid = few, if any bacteria Lepromatous = tons o' bacteria ```
66
What is the three drug regimen for leprosy?
Dapsone Clofazimine Rifampin
67
What is the MOA of dapsone?
Structural analog of PABA, that competes for folic acid synthesis in bacteria
68
What are the major side effects of dapsone?
non-hemolytic anemia if have G6PD
69
What is the MOA of Clofazimine?
DNA intercalator (maybe)
70
What are the major side effects of Clofazimine?
Red-brown to black skin discoloration

Pharm (73 decks)

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