Lecture 2: Antifungal Agents, targets, and resistance

Question 1

Are most antifungals fungi static or fungicidal

Answer 1

Fungistatic

Question 2

What are the 4 major classes of antifungals

Answer 2

1. Allylamines
2. Azoles
3. Polymers
4. Echinocandins

Question 3

What does nikkomycin do

Answer 3

Chitin synthase inhibitor

Question 4

Are allylamines broad or narrow spectrum

Answer 4

Broad

Question 5

What are the two members allylamines

Answer 5

1. Naftitine
2. Terbinafine

Question 6

Is naftittine topical or systemic

Answer 6

Topical

Question 7

Is terbinafine topical or systemic

Answer 7

Both

Question 8

What is the mechanism of action of allylamines (naftitine and terbinafine)

Answer 8

Inhibits squalene epoxidase—> increase squalene and decrease Ergosterol

Question 9

What are some adverse effects of allylamines (naftitine, terbinafine)

Answer 9

GI +/- skin disease

Question 10

Terbinafine has lipophilic properties that allow it to concentrate in __

Answer 10

Dermis/epidermis, adipose tissue, hair and nails

Question 11

Is terbinafine broad or narrow

Answer 11

Broad

Question 12

What are the two groups of the azoles

Answer 12

Imidazoles, triazoles

Question 13

Are azoles narrow or broad spectrum

Answer 13

Broad

Question 14

What is the mechanism of action of azoles

Answer 14

Inhibit sterol 14-alpha demethylase—> decrease Ergosterol—> slowed growth

Question 15

What patients are azoles contraindicated in

Answer 15

Teratogenic-pregnant animals

Question 16

What are 2 examples of imidazoles

Answer 16

Ketoconazole, miconazole

Question 17

What are two examples of triazoles

Answer 17

Fluconazole, itraconazole

Question 18

Triazoles vs imidazoles: greater affinity for fungal membranes and fever side effects

Answer 18

Triazoles

Question 19

What is fluconazole effective against

Answer 19

dermatophytes, candida, cryptococcus

Question 20

Are polyenes broad or narrow spectrum

Answer 20

Broad

Question 21

What is the mechanism of action of amphotericin B (Polyenes)

Answer 21

Binds to sterols/ Ergosterol

Question 22

What is an adverse effective of polyenes/ amphotericin B

Answer 22

Nephrotoxicity

Question 23

Are nikkomycins narrow or broad spectrum

Answer 23

Narrow

Question 24

What is the MOA of nikkomycin Z

Answer 24

Pyrimidine nuceloside similar to chitin precursor, binding chitin synthase and inhibiting its activity

Question 25

What is nikkomycin effective against

Answer 25

Cryptococcus and other dimorphic fungi

Question 26

Are nikkomycins systemic or topical

Answer 26

Systemic

Question 27

What is the mechanism of action of griseofulvin

Answer 27

Interferes with microtubule formation, disrupt mitotic spindle, inhibiting mitosis

Question 28

Griseofulvin requires pairing with __ or __ to enhance GI uptake

Answer 28

High fat meals or propylene glycol

Question 29

What patients should griseofulvin be avoided in

Answer 29

Pregnant cats and horses- teratogenic

Question 30

Is griseofulvin systemic or topical

Answer 30

Systemic

Question 31

Is flucytosine narrow or broad spectrum

Answer 31

Narrow- yeasts primarily

Question 32

What are some side effects of flucytosine

Answer 32

Hepatic/hematologic side effects

Question 33

Are iodides broad or narrow spectrum

Answer 33

Narrow

Question 34

How do you give sodium iodide to patients

Answer 34

IV

Question 35

How do you give potassium iodide to patient

Answer 35

Oral (NEVER IV)

Question 36

Prolonged use of iodides may result in iodism which can result in

Answer 36

Salivation, lacrimation, increase respiratory secretions, in appearance, dry scaly skin, tachycardia, cardiomyopathy, inhibited immune defense, infertility and abortion

Question 37

What host factors influence antifungal therapy outcomes

Answer 37

1. Immune status 2. Age and nutritional status 3. Other therapeutic treatments that affect immune response

Question 38

What fungal pathogen factors influence antifungals therapy outcome

Answer 38

1. Site and severity of infection 2. Virulence factors

Question 39

What factors of antifungal drugs influence antifungal therapy outcome

Answer 39

1. Activity and site of infection 2. Drug selection and dosing

Question 40

What are some ways in which poor access of the drug to fungal target can cause tx failure and/or relapse

Answer 40

Granuloma, immunoprivileged sites, isolation in cells, rigid wall of chitin, capsular slim layer

Question 41

What is a main reason tx fungal infections is so hard

Answer 41

Discontinuation of therapy after resolution of clinical signs, before fungal eradication

Question 42

T or F: antifungal resistance develops more slowly compared to antibacterial resistance

Answer 42

True