Antifungal Pharmacology

What are the types of fungi

Yeasts 

Dimorphs 

Dermatophytes

What type of carbon containing compounds have antifungal activity

Odd carbon containing

What are the chemical classes

Fatty acids

Phenol derivatives 

Azoles 

Nucleic Acid base derivatives

Antifungal antibiotics 

Allylamines

Polyenes

Echinocandins

What is the first azole antifungal

Clotrimazole

What is the MOA of Azoles

Alter fungal membrane permeability; inhibittion of demethylation of langesterol

inhibits ergosterol synthesis

N3 atom binds to ferric iron

What is the antimicrobial spectrum of azoles

broad spectrum 

Ex of imidazoles

clotrimazole, miconazole, bifonazole, butoconazole, ketoconazole

Ex of triazoles

itraconazole, fluconazole, terconazole, voriconazole

Explain the structural advantages of posaconzazole

Extended side chain

More potent inhibitor of sterol C14 demethylation

What is Isavuconazonium

Prodrug 

MOA of Isavuconazonium

Inhibits synthesis of ergosterol thorugh inhibition of cyp 450

Side arm gives it a broader antifungal activity

What is Flucytosine used for

Serious sytemic fungal infectionsM

MOA of Flucytosine

Incorporated into RNA then deaminated 

Inhibits Thymidylate synthetase

What is a serious toxicity associated with Flucytosine

Bone marrow toxicity

NVD

MOA of Griseofulvin

Inhibits fungal mitosis through disruption of miotitic spindle

For superficial dermatophyte infections

MOA of Polyenes

Binds to plasma membrane and increases permeability of membrane 

Ex of Polyenes

Nystatin

Amphotericin

Are Nystatin and Amphotericin orally absorbed

NO

Allyamines MOA

Squaline epoxidase inhibitors

Examples of Allylamines

Naftifine

Terbinafine

What does Echinocandins treat

Invasisve aspergillosis

MOA of Echinocandins

Disrupts creation of fungal cell walls by inhibiting synthesis of glucan which is important for cell wall synthesis