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Clinical Pharm Exam 3 > Anti-fungals > Flashcards

Anti-fungals Flashcards

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1
Q

2 basic forms of fungi

A

Yeast and mold

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2
Q

Shape of yeast

A

Single, small, oval cells

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3
Q

Shape of molds

A

Filamentous strands (hyphae)

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4
Q

Examples of yeasts

A

Candida spp., cryptococcus spp.

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5
Q

Examples of molds

A

Aspergillus spp.

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6
Q

Define dimorphic fungi

A

Species exists as either yeast or mold depending on external environment

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7
Q

What is thermal dimorphism?

A

Switch from mold form at ambient temperature to yeast form at body temperature
- Genetically controlled

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8
Q

RF for invasive fungal infections (6)

A
  • Hematologic malignancies
  • BM transplant
  • Solid organ transplant
  • Pt on corticosteroids or immunosuppressant meds
  • Burn pts
  • AIDs pts
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9
Q

Common primary care fungi

A

C. albicans & non-albicans candida

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10
Q

Examples of non-albicans candida spp.

A
  • C. krusei
  • C. glabrata
  • C. guilliermondii
  • C. lusitaniae
  • C. tropicalis
  • C. pseudotropicalis
  • C. parasilosis
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11
Q

Resistance: C. krusei

A

Inherently resistent to fluconazole

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12
Q

Resistance: C. glabrata

A

Relatively resistent to fluconazole

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13
Q

Resistance: C. guilliermondii and C. lusitaniae

A

Inherently resistent to amphotericin B

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14
Q

Anti-cell wall agent

A

Echinocandins

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15
Q

Examples of echinocandins

A
  • Caspofungin
  • Micafungin
  • Anidulafungin
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16
Q

Echinocandins MOA

A

Inhibit synthesis of B(1,3)-D-glucan (an essential component of cell wall of susceptible fungi)

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17
Q

Why is there low potential for toxicity with echinocandins humans?

A

Mammalian cells do not require B(1,3)-D-glucan

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18
Q

Echinocandin role in UTI therapy

A

Generally CANNOT use

- Not excreted in urine

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19
Q

Clinical indications for echinocandins

A
  • Invasive candida infections (including most non-albicans candida)
  • Aspergillus
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20
Q

How common is resistance against echinocandins?

A

Relatively rare

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21
Q

Anti-cell membrane agents

A
  • Polyenes
  • Azoles
  • Allylamines
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22
Q

Examples of polyenes

A
  • Amphotericin B products

- Nystatin

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23
Q

Amphotericin B products

A
  • Conventional amphotericin B
  • Amphotericin B lipid complex
  • Liposomal amphotericin B
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24
Q

Which amphotericin B product is best tolerated?

A

Liposomal amphotericin B (but it’s $$$)

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25
Indications for topical nystatin
- OP candidiasis | - Intertrigo
26
Polyenes MOA
Binds to ergoesterol -> alter cell membrane permeability -> leakage of cell components -> cell death
27
Sx that occur during infusions of polyenes
Fever, chills, rigors
28
Why do pt. experience sx during infusion of polyenes?
Directly stimulate monocytes/macrophages to release proinflammatory cytokines
29
Drug interactions polyenes
Other nephrotoxic drugs
30
Clinical indications of polyenes
- Aspergillosis - Zygomycosis - Histoplasmosis - Blastomycosis - Coccidioidomycosis - Cryptococcus - Sporothrichosis
31
Polyene ADRs (common)
- F/C/rigors - HA, N/V, decreased BP, tachypnea * Usually occur 1-3hrs into infusion & last 1 hr.
32
Treatment of common/infusion associated ADRs
Pretreat w/ APAP, diphenhydramine, meperidine +/- hydrocortisone
33
Polyene ADRs (dose-limiting)
- Nephrotoxicity | - Electrolyte abnormalities
34
Treatment of dose-limiting polyene ADRs
- Pre & post-infusion hydration (500mL NS) - Avoid concomitant nephrotoxins - Continuous infusion may mitigate - Monitor SCr, K, Mg (may decrease)
35
Examples of azoles
- Ketoconazole - Clotrimazole - Econazole - Miconazole - Terconazole - Tioconazole - Fluconazole - Itraconazole - Voriconazole - Posaconazole - Isavuconazole
36
Topical "oral" azoles
- Clotrimazole | - Miconazole
37
Topical "skin" azoles
- Ketoconazole - Clotrimazole - Econazole - Miconazole
38
Topical "vaginal" azoles
- Clotrimazole - Miconazole - Terconazole - Tioconazole
39
OLD systemic azoles
- Ketoconazole - Fluconazole - Itraconazole
40
NEW systemic azoles
- Voriconazole - Posaconazole - Isavuconazoium
41
Bolded azoles from lecture
- Clotrimazole (oral, skin, vaginal) - Miconazole (vaginal) - Fluconazole (OLD systemic azole; available PO & IV)
42
Fluconazole MOA
Inhibit fungal CYP450 enzyme which converts lanosterol -> ergosterol (cell membrane); leads to cell lysis
43
Fluconazole MOR
- Mutations in 14a-demethylase (enzyme that converts lanosterol to ergosterol) - Efflux pumps
44
Fluconazole is a strong INHIBITOR of CYP___, ____, and ____
2C9, 2C19, and 3A4
45
Fluconazole pharmacology
- Renally excreted (80% unchanged) - >90% bioavailability - 30 hr half life
46
Clinical indications of fluconazole
- Candida infections (thrush, vaginitis, cutaneous, "invasive")
47
In what population do we avoid the use of fluconazole?
Women TRYING to become pregnant & pregnant women
48
What should we use instead of fluconazole for pregnant women with vaginal candidiasis?
Clotrimazole (or other "vaginal" azoles)
49
Implications of fluconazole use in pregnancy
- Birth defects | - 1-2 doses linked to miscarriage in 1st and 2nd trimester
50
Birth defects associated with use fluconazole in pregnancy
- Short, broad head - Abnl looking face - Abnl development of the skullcap - Oral cleft (lip or palate) - Bowing of the thigh bones - Thin ribs and long bones - Muscle weakness and joint deformities - CHD
51
Example of allylamines
Terbinafine
52
Terbinafine MOA
Inhibits squalene epoxidase -> inhibits ergosterol synthesis -> deficient cell membrane -> cell death
53
Terbinafine is a strong INHIBITOR or CYP___
2D6
54
What happens when terbinafine is taken orally?
Deposits in skin/nails resulting in relatively low bloodstream concentration
55
Clinical indications of terbinafine
- Cutaneous dermatophyte infections (topical) | - Onychomycosis (PO)
56
How long do we treat onychomycosis of the fingernails? Toe nails? And WHY?
Finger nails = 6 wks Toe nails = 12 wks *it takes months for nail to grow out
57
Terbinafine ADRs
- Dysgeusia (may persist after drug cessation) | - Hepatotoxicity
58
What do we do to monitor pt. on terbinafine?
Baseline LFT + "periodically" while on the drug
59
Category B antifungals
- Amphotericin - Clotrimazole (skin, vaginal) - Allylamines
60
Category C antifungals
- Echinocandins | - Most azoles
61
Category D antifungals
Fluconazole

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