Lecture 2: Antifungal Agents, targets, and resistance Flashcards
Are most antifungals fungi static or fungicidal
Fungistatic
What are the 4 major classes of antifungals
- Allylamines
- Azoles
- Polymers
- Echinocandins
What does nikkomycin do
Chitin synthase inhibitor
Are allylamines broad or narrow spectrum
Broad
What are the two members allylamines
- Naftitine
- Terbinafine
Is naftittine topical or systemic
Topical
Is terbinafine topical or systemic
Both
What is the mechanism of action of allylamines (naftitine and terbinafine)
Inhibits squalene epoxidase—> increase squalene and decrease Ergosterol
What are some adverse effects of allylamines (naftitine, terbinafine)
GI +/- skin disease
Terbinafine has lipophilic properties that allow it to concentrate in __
Dermis/epidermis, adipose tissue, hair and nails
Is terbinafine broad or narrow
Broad
What are the two groups of the azoles
Imidazoles, triazoles
Are azoles narrow or broad spectrum
Broad
What is the mechanism of action of azoles
Inhibit sterol 14-alpha demethylase—> decrease Ergosterol—> slowed growth
What patients are azoles contraindicated in
Teratogenic-pregnant animals
What are 2 examples of imidazoles
Ketoconazole, miconazole
What are two examples of triazoles
Fluconazole, itraconazole
Triazoles vs imidazoles: greater affinity for fungal membranes and fever side effects
Triazoles
What is fluconazole effective against
dermatophytes, candida, cryptococcus
Are polyenes broad or narrow spectrum
Broad
What is the mechanism of action of amphotericin B (Polyenes)
Binds to sterols/ Ergosterol
What is an adverse effective of polyenes/ amphotericin B
Nephrotoxicity
Are nikkomycins narrow or broad spectrum
Narrow
What is the MOA of nikkomycin Z
Pyrimidine nuceloside similar to chitin precursor, binding chitin synthase and inhibiting its activity
What is nikkomycin effective against
Cryptococcus and other dimorphic fungi
Are nikkomycins systemic or topical
Systemic
What is the mechanism of action of griseofulvin
Interferes with microtubule formation, disrupt mitotic spindle, inhibiting mitosis
Griseofulvin requires pairing with __ or __ to enhance GI uptake
High fat meals or propylene glycol
What patients should griseofulvin be avoided in
Pregnant cats and horses- teratogenic
Is griseofulvin systemic or topical
Systemic
Is flucytosine narrow or broad spectrum
Narrow- yeasts primarily
What are some side effects of flucytosine
Hepatic/hematologic side effects
Are iodides broad or narrow spectrum
Narrow
How do you give sodium iodide to patients
IV
How do you give potassium iodide to patient
Oral (NEVER IV)
Prolonged use of iodides may result in iodism which can result in
Salivation, lacrimation, increase respiratory secretions, in appearance, dry scaly skin, tachycardia, cardiomyopathy, inhibited immune defense, infertility and abortion
What host factors influence antifungal therapy outcomes
- Immune status
- Age and nutritional status
- Other therapeutic treatments that affect immune response
What fungal pathogen factors influence antifungals therapy outcome
- Site and severity of infection
- Virulence factors
What factors of antifungal drugs influence antifungal therapy outcome
- Activity and site of infection
- Drug selection and dosing
What are some ways in which poor access of the drug to fungal target can cause tx failure and/or relapse
Granuloma, immunoprivileged sites, isolation in cells, rigid wall of chitin, capsular slim layer
What is a main reason tx fungal infections is so hard
Discontinuation of therapy after resolution of clinical signs, before fungal eradication
T or F: antifungal resistance develops more slowly compared to antibacterial resistance
True
