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MED234 Respiratory > Fitz, Antifungals > Flashcards

Fitz, Antifungals Flashcards

(52 cards)

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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)

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

Bugs that Voriconazole covers (3)

Study These Flashcards
A
  • Candida albicans, other candida

- DOC: Invasive Asperigillus

23
Q

Mechanisms of fungal resistance to azoles.

Study These Flashcards
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).

Study These Flashcards
A

Echinocandins —> Caspofungin, Micafungin, anidulafungin.

25
MOA of echinocandins
Inhibit cell wall synthesis by inhibiting synthesis of Beta-(1,3)-glucan, leading to osmotic fragility.
26
Echinocandin method of administration and relative tolerance.
All are infused and are well tolerated (none are oral).
27
Metabolization of caspofungin
Hepatic (so can give in renal insufficient patients, dialysis, etc).
28
Use caspofungin/echinocandins for what fungi?
Serious opportunistic infections: - Invasive candidiasis, candidemia - Invasive ASPERGILLOSIS.
29
An AIDS pt has oropharyngeal candiasis and fails fluconazole, amphotericin B, and itraconazole. What antifungal should be administered?
Caspofungin (echinocandin)
30
What are echonocandins NOT effective against?
NOT effective against pathogenic fungal organisms - Histoplasmosis - Coccidiomycosis - Fusarium spp.
31
Histoplasmosis is endemic to what region of the US? | DOC for this?
Central, and in locations with humid/warm soild and migratory birds. * *most common * *Itraconazole is DOC
32
Name this 4 opportunistic infections that are therapeutic indications for Triazoles
- Aspergillus - Rhizopus - Cryptococcus - Candida
33
Name this 4 pathogenic infections that are therapeutic indications for Triazoles
- Histoplasmosis - Coccidiomycosis - Bastomycosis - Paracoccidiodies
34
Oropharyngeal Candidasis (thrush), or immunocompromised, use what?
Itraconazole
35
Most fatal mycoses in Non-HIV patients.
Aspergillosis
36
Admin method of Ketoconazole
Pill
37
Dissolution of what two antifungals require gastric acidity?
- Pill-form of ketoconazole | - Itraconazole
38
What is a ketoconazole drug interaction?
Inhibits CYP450 drug interactions
39
A person starts taking an antifungal and comes back with decreased libido and gynecomastia. What drug was given?
Ketoconazole - Inhibits adrenal and gonadal steroid synthesis
40
Do imidazoles or triazoles disrupt testosterone synthesis?
Imidazoles. | triazoles have no endocrine abnormalities.
41
What two triazoles are strong inhibitors of hepatic CYP450 and enhance renal toxicity?
Voriconazole and Itraconazole
42
Vision disturbance, think what triazole.
voriconazole
43
When should triazoles be avoided and what damage can they cause?
Avoid in pregnancy. | All can damage liver.
44
DOC for mucormycosis
Amphotericin B
45
DOC for cryptococcal meningitis
Amphotericin B + 5-Fluorocytosine antimetabolite
46
5-FdUMP inhibits what
5-FdUMP inhibits Thymidylate Synthase = inhibition of DNA synthesis
47
5-FUTP inhibits what
5-FUTP inhibits protein synthesis
48
5-FC MOA
5-FC extracellular --(membrane bound Cytosine Permease)--> 5-FC intracellular --(cytosine deaminase)--> 5-FU ---> 5-FUMP ---> 5-FdUMP or 5-FUTP
49
Mechanisms of resistance of 5-FC
1. Intrinsic - mutation in Cytosine Permease | 2. Acquired Resistance - mutation in Cytosine Deaminase
50
How do AMP-B and 5-FC work together?
Amp-B creates ergosterol pores so that more 5-FC can get in.
51
DOC for invasive fungal infection, unresponsive to other therapy
Amp-B
52
Name this fungus: | "excessive hyphal growth and dissemination"
Aspergillosis

MED234 Respiratory (15 decks)

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