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Pharmacology > EXAM #4: ANTIFUNGALS > Flashcards

EXAM #4: ANTIFUNGALS Flashcards

1
Q

List the systemic fungi.

A
  • Histoplasma capsulatum
  • Blastomyces dermatiditis
  • Coccidioides immitis
  • Sporothrix schenckii
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2
Q

List the opportunistic fungi.

A
  • Candida
  • Aspergillus
  • Cryptococcus neoformans
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3
Q

What are the common cutaneous and subcutaneous fungal infections?

A 
Sporothrix schenckii 
Dermatophytes 
- Ringworm
- Athlete's Foot 
- Onychomycosis
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4
Q

What are the unique targets used in antifungal therapy?

A
  • Fungal cell membrane i.e. ERGOSTEROL

- Fungal cell wall i.e. GLUCANS

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5
Q

List the drugs that inhibit Ergosterol synthesis.

A

Azoles
Naftidfine
Terbnafine

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6
Q

What drug inhibits fungal membrane function?

A

Amphotericin B

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7
Q

What drug inhibits fungal cell wall synthesis?

A

Caspofungin

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8
Q

What drug inhibits fungal nuclei acid synthesis?

A

5-fluorocytosine

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9
Q

What drugs can be used to treat systemic fungal infections?

A

1) Polyenes- amphotericin B
2) Azoles
3) Flucytosine
4) Echinocandins

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10
Q

What drug has the broadest spectrum of all the antifungals?

A

Amphotericin B

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11
Q

Why has Amphotericin B been replaced for newer compounds?

A

High degree of toxicity

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12
Q

What is the MOA of Amphotericin B

A
  • Binds ergosterol in fungal cell membrane

- Forms Amp B pores in fungal membrane

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13
Q

Why is there high toxicity associated with Amphotericin B?

A

Not only binds ergosterol, but can also bind cholesterol

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14
Q

What is Amphotericin B the treatment of choice for?

A

1) Disseminated candidasis
2) Cryptococcal (neoformans) meningitis

Note that it is a second line treatment for systemic disease caused by molds

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15
Q

What is the mechanism of resistance of Amphotericin B?

A

Decreased membrane ergosterol concentration

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16
Q

How is Amphotericin B administered?

A
  • Note that it is INSOLUBLE in water*
  • Complex-ed to a bile salt
  • Given IV
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17
Q

How is Amphotericin B administered for Cryptococcal meningitis?

A

Intrathecal

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18
Q

What are the adverse reactions seen with Amphotericin B?

A

1) Infusion reaction seen in nearly all patients

2) NEPHROTOXICITY

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19
Q

How is the toxicity of Amphotericin B being combated?

A

Packaging the drug in lipid micelle i.e. “liposomal packaging”

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20
Q

What are the two groups of Azoles?

A

1) Imidazoles (2x nitrogens)

2) Triazoles (3x nitrogens)

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21
Q

List the imidazoles.

A

Ketoconazole
Miconazole
Clotrimazole

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22
Q

List the triazoles.

A

Fluconazole
Itraconazole
Voriconazole
Posaconazole

23
Q

What is the MOA of the azoles?

A

Inhibit the enzyme the produces ergosterol

- Makes the cell membrane leaky

24
Q

What are the mechanisms of resistance to the azoles?

A

1) Drug efflux pumps
2) Mutation in target enzyme
3) Decreased ergosterol synthesis

25
Q

Why is Ketoconazole rarely used clinically today?

26
Q

What is the typical first line drug for systemic fungal infections?

A

Fluconazole

27
Q

Why is Fluconazole highly utilized in the treatment of systemic fungal infections?

A
  • Highest TI
  • Distributed to the CNS
  • Few drug-drug interactions
28
Q

What is Fluconazole a first ling agent for?

A

1) Systemic Candidiasis
2) Cryptococcosis
3) Coccidiomycosis

29
Q

How does Itraconazole compared to Fluconazole?

A

Broader spectrum of activity BUT lower TI

30
Q

What does Itraconazole require for absorption?

31
Q

Can Itraconazole penetrate the CNS?

32
Q

What is Itraconazole the drug of choice for?

33
Q

What is Voriconazole?

A

Derivative of Fluconazole

34
Q

What is Voriconazole commonly used to treat?

A

Aspergillosis

Note that it has replaced Amphotericin B as the first line drug b/c of lower toxicity.

35
Q

What is the major adverse reaction associated with Voriconazole?

A

Visual disturbances

36
Q

What drug has the broadest spectrum of all the azoles?

A

Posaconazole

37
Q

What is Posaconazole used to treat?

A

Mucromycoses

Aspergillus

38
Q

What is the MOA of Flucytosine?

A

This is a fluorinated pyrimidine analog that inhibits DNA synthesis

39
Q

What is Flucytosine used to treat?

A

Used as a combination therapy for severe Cryptococcal infections

40
Q

What are the adverse reactions seen with Flucytosine?

A

Bone marrow supression i.e.

  • Anemia
  • Leukopenia
  • Thrombocytopenia
41
Q

What is the MOA of the Echinocandins?

A

Inhibit the synthesis of Beta-glucan i.e. inhibit the CELL WALL

We don’t have Beta-glucan; thus, very low toxicity

42
Q

List the Echinocandins.

A

Caspofungin
Micafungin
Andidulafungin

43
Q

What are the Echinocandins primarily used to treat?

A

Aspergillus
Candida

Note that both have a high degree of Beta-glucan in their cell wall

44
Q

What is Griseofulvin used to treat?

A

This is an oral agent used to treat Dermatophyte infections

45
Q

What is unique about Griseofulvin?

A

Concentrates in Keratin precursor cells

  • Skin
  • Hair
  • Nails
46
Q

What are Allylamines?

A

Class of antifungal that inhibits ergosterol synthesis

47
Q

What is the MOA of Allylamines?

A

Inhibit the enzyme squalene epoxidase

48
Q

What is the hallmark Allylamine?

A

Terbinafine

49
Q

What is Terbinafine used to treat?

A

First line for Onychomycosis i.e. nail infections

50
Q

What are the topical antifungal agents?

A 
Nystatin- polyene 
Clotrimazole- azole 
Miconazole- azole 
Terbinafine- Allylamine
Naftifine- Allylamine
51
Q

What is the MOA of Nystatin?

A

Polyene that binds ergosterol and forms pores

- Only used topically

52
Q

What is Nystatin used to treat?

A

Candida

  • Oral
  • Vagial i.e. yeast infections
53
Q

What are the topical azoles, Clotrimazole and Miconazole used to treat?

A

1) Vulvovaginal candidiasis
2) Dermatophyte infections
3) Oral thrush

54
Q

What infections are the topical Allylamines used to treat?

A 
Tinea curis (jock-itch) 
Tinea corporis (ringworm)

Pharmacology (64 decks)

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