DA2 Exercise 4 Lecture 6: Antifungal Agents Overview (CAO)

Rifampine targets what step of the cell cycle

Transcription

Cholesterol analogue present in fungal cell walls?

Ergosterol

Four risk factors for fungal infection?

1. Cell or organ transplant

2. Induction by chemotherapy

3. Malnutrition

4. Overuse of antibiotics

Anything that provides an opportunity for fungi to capitalize on

Describe ergosterol synthesis

Acetyl CoA -> HMG CoA -> Mevalonate -> Squalene -> Lanosterol -> Ergosterol

Squalene epoxidase forms lanosterol

14a-sterol demethylase forms ergosterol

What anti-fungals inhibit squalene epoxidase? (two classes)

Allylamines

Benzylamines

What anti-fungals inhibit 14a-sterol demethylase? (two classes)

Imidazoles

Triazoles

Which drug classes target the fungal endoplasmic reticulum (inhibit ergosterol synthesis)? (four classes)

Allylamines

Benzylamines

Imidazoles

Triazoles

What drug class targets the fungal mitotic spindle?

Griseofulvin

What drug class targets fungal DNA synthesis?

Flucytosine

What drug class targets the fungal plasma membrane?

Polyenes (amphotericin B)

What drug class targets the fungal cell wall?

Echinocandins

What are the building blocks for ergosterol synthesis?

Acetyl CoA

Squalene is converted to lanosterol by the action of what enzyme?

Squalene epoxidase

Lanosterol is converted to ergosterol by the action of what enzyme?

14a-sterol demethylase

14a-sterol demethylase is also known as what?

Fungal CYP450

Two triazole examples provided on slide?

Fluconazole

Voriconazole

Flucytosine inhibits what in fungi?

DNA synthesis

Griseofulvin inhibits what process in fungi by what mechanism?

Inhibits fungal mitosis by disrupting mitotic spindles

How do polyenes disrupt plasma membrane integrity?

Bind sterol in the fungal membrane

Fluorocytosine MOA?

Target fungal DNA synthesis

T/F: Fluorocytosine is most toxic in humans of the antifungal drugs because it can also target human DNA synthesis.

True