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Immunity, Infection and Disease > Antimycobacterial Drugs > Flashcards

Antimycobacterial Drugs Flashcards

1
Q

90 pct of primary tb infections lead to latent, asymptomatic tb. What causes this to happen?

A

Development of cell-mediated immunity (which keeps the Tb in check)

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2
Q

Are pts with latent Tb contagious?

A

No

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3
Q

How large does the induration have to be for a PPD test to be positive?

A

Immunocompromised pts or suspicion of Tb - gt 5 mm, Low risk populations - gt 15 mm, All others - gt 10 mm

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4
Q

There is an alternative to PPD for testing for Tb. What is the alternative and for whom is it recommended?

A

T cell-based inteferon gamma testing. Recommended for those who received BCG vaccine or those unlikely to return for PPD reading

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5
Q

List first line drugs for Mycobacterium tuberculosis

A

Isoniazid, Rifampin, Ethambutol, Pyrazinamide, Streptomycin

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6
Q

List second line drugs for Mycobacterium tuberculosis

A

Ethionamide, Capreomycin, Cycloserine, Aminosalicylic acid (PAS), Kanamycin, Amikacin, Quinolones (cipro, levofloxacin, moxifloxacin)

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7
Q

One anti-tb drug is recommended for use during entire duration of therapy due to efficacy, tolerability, and low cost. Which drug?

A

Isoniazid

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8
Q

Is isoniazid bactericidal or bacteriostatic?

A

Bactericidal

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9
Q

What is the mechanism of isoniazid (INH)?

A

Prodrug, converted by mycobacteria to active form, inhibits mycolic acids, which mycobacteria need for cell wall

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10
Q

AEs of isoniazid

A

Peripheral neuropathy (due to altered vit B6 metabolism) and Hepatitis (can be fatal)

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11
Q

When treating tb is rifampin bactericidal or bacteriostatic?

A

Bactericidal

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12
Q

Mechanism of rifampin

A

Binds to beta subunit of bacteria DNA-dependent RNA pol

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13
Q

AEs of rifampin

A

Drug-drug interactions (CYPs), imparts orange color to urine, sweat and tears. Also GI upset

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14
Q

Is pyrazinamide bactericidal or bacteriostatic?

A

Bactericidal in acid environments (such as where tb lives, in phagosomes of macrophages)

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15
Q

Mechanism of pyrazinamide

A

Inhibits mycolic acid biosynthesis by targeting fatty acid synthase I gene

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16
Q

AEs of pyrazinamide

A

Hepatotoxicity and hyperuricemia (may induce gout)

17
Q

Is ethambutol bactericidal or bacteriostatic?

A

Bacteriostatic

18
Q

echanism of ethambutol

A

Disrupts polymerization of cell wall

19
Q

What effect does ethambutol administration have on rifampin and ofloxacin activity

A

Increases their anti-tb activity by disrupting the cell wall (they are lipophilic)

20
Q

AEs of ethambutol

A

Decrease in visual acuity and loss of discrimination between green and red (dose-dependent)

21
Q

To what does streptomycin bind

A

The S12 subunit of ribosomal proteins (different target than other aminoglycosides)

22
Q

Is the effect of streptomycin on tb bactericidal or bacteriostatic?

A

Bacteriostatic (has bactericidal effects in vitro, but not enough reaches the tb to be cidal)

23
Q

When is streptomycin primarily used in tb cases now?

A

For drug-resistant TB or when pts are unable to take oral meds (its only available IM and IV)

24
Q

Compared to rifampin, rifabutin has more AEs and slightly worse tb activity. In what cases of tb would it be preferred over rifampin despite this?

A

In HIV positive patients also taking protease inhibitors, clarithromycin and azole antifungals, because it has far fewer drug-drug interactions

25
Q

Rifampin is a first line drug for tb. What two other first line anti-tb drugs are similar to rifampin

A

Rifabutin - same MoA and resistance, Rifapentine - same efficacy and side effect profile (but longer half-life)

26
Q

Ethionamide is a 2nd line drug for tb. What is its mechanism and what are its AEs?

A

Inhibits mycolic acid synthesis. Intense GI irritation, postural hypotension, mental depression, asthenia

27
Q

Para-aminosalicylic Acid (PAS) is a 2nd line anti-tb drug. What is its mechanism and what are its AEs?

A

Folate synthesis antagonist (similar to sulfonamides). Severe gastric irritation (limits compliance) and hypersensitivity reactions

28
Q

Which second line tb drug is associated with high incidence of ototoxicity and nephrotoxicity?

A

Capreomycin

29
Q

Cycloserine is a second line anti-tb drug. Give the mechanism and AEs of cycloserine

A

Inhibits incorporation of d-alanine into bacterial cell walls. AEs are neuologic (somnolence, vertigo, confusion, psychosis). Only used in treatment failures

30
Q

Which drugs of the same class as streptomycin are used as second line anti-tb agents?

A

Amikacin and Kanamycin (are both proper aminoglycosides) and capreomycin (is often grouped with the aminoglycosides)

31
Q

What drugs are typically used in the initial phase (2 months) and the follow up phase (4 or 7 months) for treating Tb?

A

Initial - Isoniazid, Rifampin, Pyrazinamide, Ethambutol (or streptomycin in children), Follow up - just Isoniazid and Rifampin

32
Q

What drugs are used to treat leprosy?

A

Dapsone, Rifampin and Clofazimine. Also ofloxacin, minocycline, thalidomide, and ethionamide

33
Q

Dapsone is used to treat leprosy. What are the mechanism and AEs of dapsone?

A

Mechanism similar to sulfonamides. AEs include hemolysis (high doses) and Jarish-Herxheimer reaction (immune response to sudden increase in bacterial kill products)

34
Q

What is ROM therapy?

A

Rofampin-Ofloxacin-Minocycline. Advocated by WHO as single dose therapy for a single paucibacillary (tuberculoid leprosy) skin lesion

35
Q

Treatment of mycobacterium avium-intracellulare complex (MAC) in HIV-negative patients

A

Clarithromycin (or azithromycin), Ethambutol, and Rifampin for one year after cultures are negative

36
Q

Treatment for mycobacterium kansasii

A

INH, rifampin, and ethambutol for 12-18 months

37
Q

Treatment for mycobacterium marinum

A

Clarithromycin or doxycycline or trimethoprim-sulfamethoxazole or rifampin and ethambutol

Immunity, Infection and Disease (86 decks)

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