Antifungals

Question 1

Amphotericin B: Mechanism of Action

Answer 1

Binds selectively to ergosterol (structurally related to cholesterol) to disrupt the fungal cell membrane function (fungicidal)

Question 2

Amphotericin B: Therapeutic Uses

Answer 2

• Used for most systemic fungal infections

- Also used to treat leishmaniasis (protozoan)

Question 3

Amphotericin B: Spectrum

Answer 3

Broad spectrum of antifungal activity

Question 4

How is Amphotericin B given?

Answer 4

Not absorbed orally; MUST be given IV

Question 5

Amphotericin B: Adverse Effects

Answer 5

• Nephrotoxicity

- Lipid formulations have reduced renal toxicity

Question 6

Echinocandins (Caspofungin): Mechanism of Action

Answer 6

Inhibits synthesis of cell wall polysaccharides

Question 7

Caspofungin: Therapeutic Uses

Answer 7

• Alternate therapy for serious systemic fungal infections

Question 8

How is Caspofungin given?

Answer 8

Poor oral absorption; given IV

Question 9

Flucytosine: Mechanism of Action

Answer 9

Blocks DNA synthesis by inhibiting thymidylate synthetase

Question 10

Flucytosine is a prodrug. What enzyme activates this drug?

Answer 10

Selectively activated to 5-fluorouracil by fungal-specific enzyme called cytosine deaminase

Question 11

Flucytosine: Therapeutic Uses

Answer 11

• Synergistic in combination with Amphotericin B (because the Amphotericin B disrupts the membrane, the Flucytosine will go into the cell easier)

Question 12

Flucytosine: Adverse Effects

Answer 12

• Enterocolitis

- High prolonged serum levels may cause bone marrow suppression

Question 13

Itraconazole: Mechanism of Action

Answer 13

Inhibits cytochrome P-450 mediated synthesis of ergosterol by fungi

Question 14

Itraconazole: Spectrum

Answer 14

Extended to Broad Spectrum

Question 15

Itraconazole: Drug Interactions

Answer 15

• Can increase the plasma level of other drugs (e.g. phenytoin, cyclosporin)

Question 16

Nystatin: Mechanism of Action

Answer 16

Same mechanism as Amphotericin B
- Binds selectively to ergosterol (structurally related to cholesterol) to disrupt the fungal cell membrane function (fungicidal)

Question 17

Nystatin: Therapeutic Uses

Answer 17

Only useful for the treatment of Candidiasis

Question 18

How is Nystatin given? Why doesn’t it cause toxicity?

Answer 18

Orally; because it doesn’t get absorbed well it will get expelled and limits systemic toxicity

Question 19

Miconazole: Mechanism of Action

Answer 19

Same as Itraconazole

-Inhibits cytochrome P-450 mediated synthesis of ergosterol by fungi

Question 20

Miconazole: Therapeutic Uses

Answer 20

Used to treat superficial infections (orally and topically)

Question 21

How is Miconazole given?

Answer 21

Orally for the same reason as Nystatin

Question 22

Terbinafine: Mechanism of Action

Answer 22

Inhibits ergosterol synthesis by a different mechanism than Miconazole and Itraconazole

Question 23

Terbinafine: Therapeutic Uses

Answer 23

• Taken orally for the treatment of severe or extensive superficial infections (concentrates in skin and nails)
• Can also be used topically

Question 24

What drugs are used to treat superficial fungal infections?

Answer 24

Nystatin, Miconazole, Terbinafine