Fungi

Question 1

What is a fungi?

Answer 1

Eukaryotic, heterotroph, often saphrophytic

Question 2

Yeast

Answer 2

Single cell, spherical or elliptical, reproduce asexually by budding

Question 3

Budding produces what?

Answer 3

Conidia

Question 4

Molds

Answer 4

Multicellular, form thread-like filaments call hypae

Question 5

Mycellium

Answer 5

Mass of hyphae

Question 6

Dimporphic fungi

Answer 6

Mold-cold environment, yeast-warm environment

Question 7

What do fungi produce through sexual reproduction?

Answer 7

Spores

Question 8

Hyphae filaments

Answer 8

Grow toward nutrients, can facilitate invasion

Question 9

Haustoria

Answer 9

Hyphae on parasitic fungi

Question 10

What is important issue when treating eukaryotic fungi?

Answer 10

Selective toxicity

Question 11

What are good targets for antifungal medications?

Answer 11

Cell walls–cotain chitin and glucans. Ergosterol in plasma membrane (may have some toxicity…similar to cholesterol)

Question 12

Polyenes

Answer 12

Amphotericin B and Nystatin

Question 13

Mechanism of polyenes

Answer 13

Binds ergosterol, creates holes in membrane, allow for leaking of electrolytes, bactericidal

Question 14

Spectrum of polyenes

Answer 14

Broad. Used for invasive systemic fungal infections in immunocompromised patients. Active against yeast and molds

Question 15

Polyene distribution

Answer 15

Small fraction of drug excreted, long tissue half life. Liposomal form can cross blood brain barrier!!!

Question 16

Polyene adverse effects

Answer 16

Nystatin treats Candida topically. Toxic because it is able to bind cholesterol! Decreases renal blood flow, can cause permanent destruction of basement membrane, up to 80% of patients have nephrotoxicity!

Question 17

Polyene resistance

Answer 17

Rare, decrease ergosterol in membrane

Question 18

Azoles

Answer 18

Fluconazole, Itraconazole, Ketoconazole

Question 19

Azoles mechanism

Answer 19

binds fungal P-450 enzyme (Erg11), blocking production of ergosterol and causing accumulation of lanosterol, fungistatic

Question 20

Azoles spectrum

Answer 20

Most widely used antifungal, spectrum varies by agents

Question 21

Azoles distribution

Answer 21

Orally available through cola/acid (helps facilitate absorption of itraconazole and ketoconazole)

Question 22

Azoles toxicity

Answer 22

Drug-drug interactions, hepatotoxicity, neurotoxicity, alters hormone synthesis. Avoid during pregnancy!!!

Question 23

Azoles resistance

Answer 23

Altered cytochrome P-450, upregulation of efflux transporters

Question 24

Allylamines

Answer 24

Terbinafine (Lamisil)

Question 25

Allylamines mechanism

Answer 25

Fungicidal, inhibits squalene epoxidase, leads to toxic accumulation of squalene

Question 26

Allylamines spectrum

Answer 26

Dermatophytes

Question 27

Allylamines toxicity

Answer 27

Topical, drug interactions with CYP2D6 substrates

Question 28

Allylamines resistance

Answer 28

Rare in human pathogens but could include decreased uptake, mutant binding site, and substrate for efflux transporters

Question 29

Flucytosine (5-FC) mechanism

Answer 29

Nucleic acid synthesis inhibitor. Antimetabolite secectively taken up and converted to 5-flurouracil in fungi, interfering with DNA and RNA synthesis. Fungistatic

Question 30

Flucytosine spectrum

Answer 30

Narrow-yeast. Candida albicans and cryptococcus

Question 31

Flucytosine distribution

Answer 31

Oral, penetrates the CNS

Question 32

Flucytosine toxicity

Answer 32

Only partially selective for yeast, can lead to bone marrow suppression, follow patient's cell count carefully

Question 33

Flucytosine resistance

Answer 33

Loss of converting enzyme or transporters, rarely used as monotherapy. Often cotreat with amphotericin B to increase uptake and minimize the likelihood of developing resistance

Question 34

Griseofulvin mechanism

Answer 34

Binds microtubules, inhibits spindle leading to multinucleate cells, fungistatic

Question 35

Griseofulvin spectrum

Answer 35

Dermatophytes

Question 36

Griseofulvin distribution

Answer 36

Lipids increase oral absorption and then concentrates in dead keratinized layer of the skin

Question 37

Griseofulvin toxicity

Answer 37

Teratogenic. Do NOT use if pregnant!!!

Question 38

Griseofulvin resistance

Answer 38

Change to beta-tubulin, need to take orally for months and if patient not compliant, resistance mutations more likely to occur

Question 39

Echinocandins (caspofungin) mechanism

Answer 39

Cell wall inhibitor blocks synthesis of beta (1,3)-d-glucan polysaccharide. Fungicidal for candida, fungistatic for aspergillus

Question 40

Echinocandins (caspofungin) spectrum

Answer 40

Candida albicans, system

Question 41

Echinocandins (caspofungin) distribution

Answer 41

IV, large molecular weight prohibits CNS penetration

Question 42

Echinocandins (caspofungin) toxicity

Answer 42

Limited, fever, rash at site of infection

Question 43

Echinocandins (caspofungin) resistance

Answer 43

Change in (1,3) beta D-glucan synthase gene

Question 44

What percentage of spores are capable of initiating fungal infection?

Answer 44

0.1%. Begins in lungs or on skin

Question 45

Mtcotoxicoses

Answer 45

Poisoning from toxins made by a fungus

Question 46

Mycosis

Answer 46

Fungus grows on or in the individual

Question 47

How rapidly do fungal infections develop?

Answer 47

Very slowly unless individual has suppressed immune system

Question 48

Cutaneous fungal infections

Answer 48

Malassezia (tinea versicolor) | Dermatophytes-microsporum, epidermophyton, trichophyton

Question 49

Subcutaneous fungal infections

Answer 49

Infection through skin, followed by subcutaneous or lymphatic spread (ex. Sporothrix)

Question 50

Opportunistic mycoses

Answer 50

Candida albicans part of normal flora. Infections in patients with immune deficiencies

Question 51

Diagnosis of fungal skin infection

Answer 51

Collect skin, hair, or nail with scraping. 10% KOH, can add stain, view under microscope. Some fungi fluoresce under Wood' lamp (UV-A), can also do PCR or culture