Antifungal Agents Flashcards Preview

Disease & Defense - Unit 3 > Antifungal Agents > Flashcards

Flashcards in Antifungal Agents Deck (39):
1

Amphotericin B: mechanism of action

-binds ergosterol in fungal cell membrane
-forms pores--> cell content leakage
-fungicidal

2

Amphotericin B: pharmacokinetics

-IV/topical
-renal excretion

3

Amphotericin B: clinical uses

-broad spectrum, including opportunistic and systemic
-drug of choice in all life-threatening fungal infections

4

Amphotericin B: adverse reactions

-very toxic <--less selective toxicity b/c binds to cholesterol components in mammals
-nephrotoxicity
-infusion-related toxicity=chills, fever, vomiting, rigor, hypotension
-anemia

5

Nyastatin: mechanism of action

-binds ergosterol in fungal cells

6

Nyastatin: pharmacokinetics

-topical only
-no absorption from GI

7

Nyastatin: clinical uses

-topical treatment of Candidal infections of skin, mucous, membranes

8

Nyastatin: adverse reactions

-mild GI upset

9

Types of Echinocandins

1. Capsofungin 2. Micafungin

10

Capsofungin: mechanism of action

-inhibits synthesis of Beta (1,3)-D-glucan (=component of fungal cell walls)
-disrupts cell wall assembly
-high selective toxicity

11

Capsofungin: pharmacokinetics

-IV
-hepatic metabolism
-dosage reduction w/hepatic insufficiency
-dosage increase w/co-tx w/CYP450 inducers

12

Capsofungin: clinical uses

-invasive aspergillosis in pts intolerant to other therapies

13

Capsofungin: adverse reactions

-histamine-mediated possible
-fever, nausea/vomiting, headache, phlebitis

14

Types of Triazoles

-Fluconazole
-Itraconazole
-Terconazole (topical only)

15

Triazoles: mechanism of action

-highly selective inhibitor of fungal cytochrome P450 (14alpha-demethylase)
-reduces normal sterol synthesis
-fungistatic

16

Triazoles: pharmacokinetics

-oral
-can enter CNS
-renal excretion
-long half-life=daily dosing

17

Triazoles: clinical uses

-fluconazole: vaginal candidiasis, oropharyngeal and esophageal candidiasis
-itraconazole: aspergillosis, histoplasmosis, sporotrichosis
-viraconazole: invasive aspergillosis

18

Triazoles: adverse reactions

-overall well tolerated
-GI distress
-some drug interactions similar to imidazoles

19

Types of Imidazoles

-ketoconazole (systemically and topically)
-clotrimazole (topical only)
-miconazole (topical only)

20

Imidazoles: mechanism of action

-inhibits P450 enzyme (14alpha-demethylase) -_> decreased levels of ergosterol
-disruption of membrane synthesis --> altered membrane permeability
-fungicidal

21

Imidazoles: pharmacokinetics

-ketconazole=oral and IV
-clotri/micon=topical only
-hepatic metabolism
-excreted in breast milk

22

Imidazoles: clinical uses

-keto: chronic mucocuatneous candidiasis and systemic fungal infections
-oral and vaginal cadidiasis (mico/clotri)

23

Imidazoles: adverse reactions

-ketoconazole systemically:
-nausea, vomiting, anorexia. hepatotoxicity.
-avoid in pregnancy
-can inhibit mammalian testosterone synthesis
-ketoconazole=strong inhibitor of CYP3A4 drug metabolism
-rifampin decreases ketocon effect by inducing metabolism

24

Terbinafine: mechanism of action

-ihibits squalene oxidase --> interferes w/ergosterol synthesis
-fungicidal

25

Terbinafine: pharmacokinetics

-oral and topical

26

Terbinafine: clinical uses

-oral=toe/finger nail infections
-topical=athletes foot

27

Terbinafine: adverse reactions

-GI upset
-interferes w/CYP450 metabolism

28

Flucytosine: mechanism of action

-converted in fungal cell to 5-fluorouracil --> interferes w/DNA synthesis
-high selective toxicity
-fungicidal

29

Flucytosine: pharmacokinetics

-oral
-renal excretion

30

Flucytosine: clinical uses

-effective, but rarely given alone; usually Ampho B + Flucytosine
-serious infections of cryptococcosis, candidiasis, chromoblastomycosis

31

Flucytosine: adverse reactions

-nausea, vomiting, skin rashes
-prolonged tx=bone marrow depression, abnormal liver fxn, hair loss

32

Griseofulvin: mechanism of action

-binds microtubules --> inhibits fungal mitosis and processing of cell wall components
-fungistatic

33

Griseofulvin: pharmacokinetics

-oral
-fecal excretion

34

Griseofulvin: clinical uses

-severe dermatophytosis @ skin, hair, or nails
-infrequently used, often replaced by shorter course therapy

35

Griseofulvin: adverse reactions

-hypersenstivity
-headache, GI distress

36

Pentamidine: mechanism of action

-inhibits protein/nucleic acid synthesis

37

Pentamidine: pharmacokinetics

-IV/IM
-inhalation for fungal pneumonia

38

Pentamidine: clinical uses

-effective against wide variety of protozoa
-treats P. jirovici (carinii) pneumonia in AIDS patients

39

Pentamidine: adverse reactions

-leukopenia, hypoglycemia, hypotension
-nephro/hepatotoxicity