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Clinical Pharm Exam 3 > Anti-fungals > Flashcards

Anti-fungals Flashcards

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
Q

Indications for topical nystatin

A
  • OP candidiasis

- Intertrigo

26
Q

Polyenes MOA

A

Binds to ergoesterol -> alter cell membrane permeability -> leakage of cell components -> cell death

27
Q

Sx that occur during infusions of polyenes

A

Fever, chills, rigors

28
Q

Why do pt. experience sx during infusion of polyenes?

A

Directly stimulate monocytes/macrophages to release proinflammatory cytokines

29
Q

Drug interactions polyenes

A

Other nephrotoxic drugs

30
Q

Clinical indications of polyenes

A
  • Aspergillosis
  • Zygomycosis
  • Histoplasmosis
  • Blastomycosis
  • Coccidioidomycosis
  • Cryptococcus
  • Sporothrichosis
31
Q

Polyene ADRs (common)

A
  • F/C/rigors
  • HA, N/V, decreased BP, tachypnea
  • Usually occur 1-3hrs into infusion & last 1 hr.
32
Q

Treatment of common/infusion associated ADRs

A

Pretreat w/ APAP, diphenhydramine, meperidine +/- hydrocortisone

33
Q

Polyene ADRs (dose-limiting)

A
  • Nephrotoxicity

- Electrolyte abnormalities

34
Q

Treatment of dose-limiting polyene ADRs

A
  • Pre & post-infusion hydration (500mL NS)
  • Avoid concomitant nephrotoxins
  • Continuous infusion may mitigate
  • Monitor SCr, K, Mg (may decrease)
35
Q

Examples of azoles

A
  • Ketoconazole
  • Clotrimazole
  • Econazole
  • Miconazole
  • Terconazole
  • Tioconazole
  • Fluconazole
  • Itraconazole
  • Voriconazole
  • Posaconazole
  • Isavuconazole
36
Q

Topical “oral” azoles

A
  • Clotrimazole

- Miconazole

37
Q

Topical “skin” azoles

A
  • Ketoconazole
  • Clotrimazole
  • Econazole
  • Miconazole
38
Q

Topical “vaginal” azoles

A
  • Clotrimazole
  • Miconazole
  • Terconazole
  • Tioconazole
39
Q

OLD systemic azoles

A
  • Ketoconazole
  • Fluconazole
  • Itraconazole
40
Q

NEW systemic azoles

A
  • Voriconazole
  • Posaconazole
  • Isavuconazoium
41
Q

Bolded azoles from lecture

A
  • Clotrimazole (oral, skin, vaginal)
  • Miconazole (vaginal)
  • Fluconazole (OLD systemic azole; available PO & IV)
42
Q

Fluconazole MOA

A

Inhibit fungal CYP450 enzyme which converts lanosterol -> ergosterol (cell membrane); leads to cell lysis

43
Q

Fluconazole MOR

A
  • Mutations in 14a-demethylase (enzyme that converts lanosterol to ergosterol)
  • Efflux pumps
44
Q

Fluconazole is a strong INHIBITOR of CYP___, ____, and ____

A

2C9, 2C19, and 3A4

45
Q

Fluconazole pharmacology

A
  • Renally excreted (80% unchanged)
  • > 90% bioavailability
  • 30 hr half life
46
Q

Clinical indications of fluconazole

A
  • Candida infections (thrush, vaginitis, cutaneous, “invasive”)
47
Q

In what population do we avoid the use of fluconazole?

A

Women TRYING to become pregnant & pregnant women

48
Q

What should we use instead of fluconazole for pregnant women with vaginal candidiasis?

A

Clotrimazole (or other “vaginal” azoles)

49
Q

Implications of fluconazole use in pregnancy

A
  • Birth defects

- 1-2 doses linked to miscarriage in 1st and 2nd trimester

50
Q

Birth defects associated with use fluconazole in pregnancy

A
  • 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
Q

Example of allylamines

A

Terbinafine

52
Q

Terbinafine MOA

A

Inhibits squalene epoxidase -> inhibits ergosterol synthesis -> deficient cell membrane -> cell death

53
Q

Terbinafine is a strong INHIBITOR or CYP___

A

2D6

54
Q

What happens when terbinafine is taken orally?

A

Deposits in skin/nails resulting in relatively low bloodstream concentration

55
Q

Clinical indications of terbinafine

A
  • Cutaneous dermatophyte infections (topical)

- Onychomycosis (PO)

56
Q

How long do we treat onychomycosis of the fingernails? Toe nails? And WHY?

A

Finger nails = 6 wks
Toe nails = 12 wks
*it takes months for nail to grow out

57
Q

Terbinafine ADRs

A
  • Dysgeusia (may persist after drug cessation)

- Hepatotoxicity

58
Q

What do we do to monitor pt. on terbinafine?

A

Baseline LFT + “periodically” while on the drug

59
Q

Category B antifungals

A
  • Amphotericin
  • Clotrimazole (skin, vaginal)
  • Allylamines
60
Q

Category C antifungals

A
  • Echinocandins

- Most azoles

61
Q

Category D antifungals

A

Fluconazole

Clinical Pharm Exam 3 (4 decks)

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