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MED234 Respiratory > Fitz, Antifungals > Flashcards

Fitz, Antifungals Flashcards

1
Q

Name a polyene antifungal.

A

Amphoterecin B

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2
Q

What is ergosterol?

A

Ergosterol is what yeast cell (fungi) membranes are rich in.

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3
Q

MOA of Amphoterecin B.

A

Binds to ergosterol and forms membrane pores that allow leakage of electrolytes.

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4
Q

Are the membrane pores created by Amphoterecin B hydrophilic or hydrophobic?

A

hydrophilic membrane pores.

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5
Q

What membrane structural characteristics does Amphoterecin B affect (2)?

A
  1. Disrupts membrane integrity

2. Increases osmotic fragility.

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6
Q

Toxicity of Amphoterecin B:

  1. Onset at infusion
  2. Later onset
A
  1. Chills, fever, anemia, hypotension

2. Nephrotoxicity

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7
Q

Clearance of Amphoterecin B

A

renal

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8
Q

Affects of Amphoterecin B on the kidney (2)

A

Direct DAMAGE TO DISTAL TUBULE membrane (Na/K/Mg wasting) —> leading to DECREASED GFR.

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9
Q

Amphoterecin B aggravates nephrotoxicity of other drugs in what conditions?

A

In immunocompromised - transplant, allograft, HIV, people with serious gram negative or MRSA infections.

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10
Q

Name the azoles.

A
  1. Imidazole - ketoconazole

2. Triazole - (1st gen) Fluconazole, Itraconazole; (2nd gen) Voriconazole, Posaconazole

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11
Q

MOA of azoles

A

Inhibits ergosterol synthesis, the CYP450 enzyme that converts Lanosterol (excess) —> Ergosterol (deficit)

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12
Q

Name of the CYP450 enzyme that azoles inhibit.

A

14-alpha-demethylase

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13
Q

Fluconazole spectrum (and what 2 bugs)

A

Narrow spectrum - Candida albicans, Cryptococcus

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14
Q

Clearance of Fluconazole v. Itraconazole v. Voriconazole

A

Fluconazole - RENAL (75%)
Itraconazole - hepatic
Voriconazole - hepatic

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15
Q

Absorption/bioavailability of Fluconazole v. Itraconazole v. Voriconazole

A

Fluconazole - Good (90%)
Itraconazole - Poor (50%)
Voriconazole - Good (95%)

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16
Q

CSF access of Fluconazole v. Itraconazole v. Voriconazole

A

Fluconazole - GOOD (so can cover crypto for meningitis)
Itraconazole - POOR solubility
Voriconazole - Good

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17
Q

CYP450 inhibition of Fluconazole v. Itraconazole v. Voriconazole

A

Fluconazole - Weak
Itraconazole - STRONG drug interactions
Voriconazole - Weak

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18
Q

Half life of Fluconazole v. Itraconazole v. Voriconazole

A

Fluconazole - ~24 hours
Itraconazole - ~21 hours
Voriconazole - non linear

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19
Q

What does Fluconazole NOT cover?

What azole does cover this?

A

Aspergillus

Voriconazole covers this.

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20
Q

Bugs that Fluconazole covers (2)

A

Candida albicans, cryptococcus (bc penetrates CSF)

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21
Q

Spectrum and Bugs that Itraconazole covers (5)

A
  • Broad spectrum
  • Covers: CANDIDA (Candida albicans, other candida), some aspergillus
  • DOC: Histo, coccidio, blasto
22
Q

Bugs that Voriconazole covers (3)

A
  • Candida albicans, other candida

- DOC: Invasive Asperigillus

23
Q

Mechanisms of fungal resistance to azoles.

A
  1. Mutation of lanosterol-14-alpha-demethylase
  2. Overexpression of lanosterol-14alpha-demethylase
  3. Energy-dependent efflux systems
  4. Decreased permeability of fungal membrane (changes in sterol/phospholipid composition)
24
Q

Name of fungal cell wall synthesis inhibitor class and drugs (3).

A

Echinocandins —> Caspofungin, Micafungin, anidulafungin.

25
Q

MOA of echinocandins

A

Inhibit cell wall synthesis by inhibiting synthesis of Beta-(1,3)-glucan, leading to osmotic fragility.

26
Q

Echinocandin method of administration and relative tolerance.

A

All are infused and are well tolerated (none are oral).

27
Q

Metabolization of caspofungin

A

Hepatic (so can give in renal insufficient patients, dialysis, etc).

28
Q

Use caspofungin/echinocandins for what fungi?

A

Serious opportunistic infections:

  • Invasive candidiasis, candidemia
  • Invasive ASPERGILLOSIS.
29
Q

An AIDS pt has oropharyngeal candiasis and fails fluconazole, amphotericin B, and itraconazole. What antifungal should be administered?

A

Caspofungin (echinocandin)

30
Q

What are echonocandins NOT effective against?

A

NOT effective against pathogenic fungal organisms

  • Histoplasmosis
  • Coccidiomycosis
  • Fusarium spp.
31
Q

Histoplasmosis is endemic to what region of the US?

DOC for this?

A

Central, and in locations with humid/warm soild and migratory birds.

  • *most common
  • *Itraconazole is DOC
32
Q

Name this 4 opportunistic infections that are therapeutic indications for Triazoles

A
  • Aspergillus
  • Rhizopus
  • Cryptococcus
  • Candida
33
Q

Name this 4 pathogenic infections that are therapeutic indications for Triazoles

A
  • Histoplasmosis
  • Coccidiomycosis
  • Bastomycosis
  • Paracoccidiodies
34
Q

Oropharyngeal Candidasis (thrush), or immunocompromised, use what?

A

Itraconazole

35
Q

Most fatal mycoses in Non-HIV patients.

A

Aspergillosis

36
Q

Admin method of Ketoconazole

A

Pill

37
Q

Dissolution of what two antifungals require gastric acidity?

A
  • Pill-form of ketoconazole

- Itraconazole

38
Q

What is a ketoconazole drug interaction?

A

Inhibits CYP450 drug interactions

39
Q

A person starts taking an antifungal and comes back with decreased libido and gynecomastia. What drug was given?

A

Ketoconazole - Inhibits adrenal and gonadal steroid synthesis

40
Q

Do imidazoles or triazoles disrupt testosterone synthesis?

A

Imidazoles.

triazoles have no endocrine abnormalities.

41
Q

What two triazoles are strong inhibitors of hepatic CYP450 and enhance renal toxicity?

A

Voriconazole and Itraconazole

42
Q

Vision disturbance, think what triazole.

A

voriconazole

43
Q

When should triazoles be avoided and what damage can they cause?

A

Avoid in pregnancy.

All can damage liver.

44
Q

DOC for mucormycosis

A

Amphotericin B

45
Q

DOC for cryptococcal meningitis

A

Amphotericin B + 5-Fluorocytosine antimetabolite

46
Q

5-FdUMP inhibits what

A

5-FdUMP inhibits Thymidylate Synthase = inhibition of DNA synthesis

47
Q

5-FUTP inhibits what

A

5-FUTP inhibits protein synthesis

48
Q

5-FC MOA

A

5-FC extracellular –(membrane bound Cytosine Permease)–> 5-FC intracellular –(cytosine deaminase)–> 5-FU —> 5-FUMP —> 5-FdUMP or 5-FUTP

49
Q

Mechanisms of resistance of 5-FC

A
  1. Intrinsic - mutation in Cytosine Permease

2. Acquired Resistance - mutation in Cytosine Deaminase

50
Q

How do AMP-B and 5-FC work together?

A

Amp-B creates ergosterol pores so that more 5-FC can get in.

51
Q

DOC for invasive fungal infection, unresponsive to other therapy

A

Amp-B

52
Q

Name this fungus:

“excessive hyphal growth and dissemination”

A

Aspergillosis

MED234 Respiratory (15 decks)

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