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Pulmonary > Anti-fungal drugs > Flashcards

Anti-fungal drugs Flashcards

1
Q

What drug binds to membrane ergosterol?

A

amphotericin B

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2
Q

How is amphotericin B administered?

A

topical or IV (not oral)

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3
Q

Which class of drug inhibits lanosterol demethylase? Results?

A
  • azole drugs

- inhibits ergosterol synthesis

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4
Q

Which azole drug subtype inhibits CYP450 proteins?

A

triazoles

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5
Q

Which drug directly disrupts the cell wall? When is it used?

A
  • caspofungin

- IV for azole-resistant infections

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6
Q

What drugs inhibit enoyl reductase? What is disrupted?

A
  • Isoniazid, ethionamide

- mycolic acid synthesis

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7
Q

Two AE’s associated with isoniazid?

A
  • neuritis

- hepatotoxicity

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8
Q

What enzyme is inhibited by rifampin?

A

DNA-dependent RNA polymerase

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9
Q

What is induced by rifampin?

A

CYP450

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10
Q

Difference between effectiveness of fluconazole and itraconazole?

A

similar, but flu is less effective in the lungs

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11
Q

How are blast patients typically treated?

A
  • itra/keto

- ampho

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12
Q

Benefits of triazoles over imidazoles?

A
  • tri’s last longer and have fewer cross-reactions
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13
Q

How do azole drugs work?

A
  • inhibit lanosterol demethylase, a CYP450 enzyme that is important in membrane structure and O2 transport in fungi
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14
Q

What effects can azole drugs have in humans?

A
  • inhibition of human CYP450 lanosterol demethylase

- inhibit human sterol synthesis and can alter metabolism of other drugs

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15
Q

What is a common chemotherapeutic agent whose effectiveness is decreased by azole drugs?

A
  • cyclophosphamide

- activated by CYP450

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16
Q

What class of anti-fungals are teratogens?

A

azole drugs - disrupts hormonal synthesis and inhibits aromatase

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17
Q

Differences between ketoconazole and itraconazole?

A
  • older imidazole with lots of drug interactions

- itra is newer triazole with less severe interactions

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18
Q

What 6 drugs have significant interactions with azoles?

A
  • warfarin, cyclosporine, phenytoin

- lovastatin, oral hypoglycemics, protease inhibitors

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19
Q

What drug binds to ergosterol in the fungal cell membrane and disrupts the membrane?

A

amphotericin B

20
Q

What anti-fungal is pretty useful against a BROAD spectrum of fungi?

A

amphotericin B AND it crosses the BBB

21
Q

What is the principal dose-limiting toxicity with amphotericin B?

A

renal dysfunction - also hypotension, hypokalemia, reversible normocytic anemia, thrombophlebitis

22
Q

Pharmacodynamics of azoles?

A
  • Itra and keto are highly protein-bound in the bloodstream

- Flu crosses BBB readily

23
Q

How is cocci treated? What other types of drugs should be avoided with this treatment?

A
  • amphotericin B

- anti-virals also cause renal toxicity

24
Q

What is the new SOC for invasive aspergillosis?

A

voriconazole (traditionally amphotericin)

25
Q

What class of drug is caspofungin? How does it work?

A
  • echinocandin

- non-competitively inhibits synthesis of fungal cell wall by being a lipopeptide that causes fungal cells to lyse

26
Q

What two diseases is caspofungin approved for?

A
  • invasive aspergillosis
  • esophageal candidosis
  • WHEN ampho/fluconazole have failed
27
Q

How is caspofungin administered and why?

A
  • IV

- not absorbed by GI tract

28
Q

Why must TB treatments last 6 months?

A
  • granulomatous immune response

- organisms have thick waxy coats and can form resistant little masses in the lungs

29
Q

When is ethambutol included in a TB regimen?

A

when isoniazide resistance exceeds 4%

30
Q

Standard 4 drug TB regimen?

A
  • PIER

- pyrazinamide, isoniazide, ethambutol, rifampin

31
Q

MOA of isoniazid?

A
  • inhibits enoyl reductase blocking my colic acid synthesis
32
Q

What enzyme activates isoniazid?

A

KatG - catalase/peroxidase

33
Q

What drug may inhibit uptake of isoniazid?

A

Al-containing antacids

34
Q

What enzyme metabolizes isoniazid? Who is this a problem in?

A
  • liver N-acetyl transferase

- 50% of American Caucasians and 15% of Asians are slow acetylators

35
Q

How is neuritis associated with isoniazid administration treated?

A
  • pyridoxine

- isoniazid looks like Vit B6 so large doses of B6 can displace it from non-target sites

36
Q

3 TB drugs associated with hepatotoxicity?

A
  • isoniazid
  • rifampin
  • pyrazinamide (hepatitis)
37
Q

What 4 drugs are affected by induction of CYP450 by rifampin?

A
  • prednisone, digitoxin, quinidine, propanalol
38
Q

What are the anti-TB effects of pyrazinamide?

A
  • unknown MOA

- inhibits my colic acid biosynthesis

39
Q

What are the anti-TB effects of ethambutol?

A
  • unknown MOA

- interferes with metabolism, replication

40
Q

AE associated with ethambutol?

A
  • optic neuritis = blurring, red-green perception loss

- reversible

41
Q

What TB drugs are associated with high rates of resistance?

A

isoniazid and rifampin

42
Q

What three drugs are added in second-line anti-TB therapy?

A
  • streptomycin
  • ethionamide
  • p-aminosalicylate
43
Q

How does p-aminosalicylic acid work in an anti-TB regimen?

A
  • competitive inhibitor of PABA (folate synthesis)

- specific for tubercle bacilli but has severe GI and hypersensitivity effects

44
Q

How does ethionamide work?

A
  • pro-drug that inhibits the same step as isoniazid (enoyl reductase) but by a different mechanism
  • inhibition of my colic acid synthesis
45
Q

AE’s associated with ethionamide?

A

GI effects (vs. neuritis, hepatotoxicity, rash, fever, hypersensitivity)

Pulmonary (7 decks)

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