Anti-Fungal Agents

Question 1

Name 2 polyenes antifungal

Answer 1

1. Amphotericin B

2. Nystatin

Question 2

Name the 2 categories of azole antifungals

Answer 2

1. Triazole

2. Imidazole

Question 3

What is the mechanism of action polyene antifungals?

Answer 3

They bind to ergosterol in the plasma membranes of sensitive fungal cells to forms pores (channels). These pores disrupt membrane function, allowing electrolytes and other small molecules to leak from the cell, resulting in cell death.

Question 4

How is amphotericin B commonly administered?

Answer 4

IV (poor oral bioavailability)

Question 5

What advantage does the liposomal formulation of amphotericin B has over the conventional deoxycholate formulation?

Answer 5

1. Liposomal formulation has reduced renal toxicity

Question 6

State 2 adverse effects associated with amphotericin B deoxycholate formulation

Answer 6

1. Fever and chills (Infusion related toxicity)

2. Nephrotoxicity

Question 7

Name 2 clinical indications for amphotericin B

Answer 7

1. Candidiasis
2. Aspergilliosis
3. Cryptococcal meningitis

Question 8

Name an anti-fungal, which is relatively safe for use in pregnancy despite systemic exposure.

Answer 8

Amphotericin B

Question 9

What is the mechanism of action for 5-Flucytosine?

Answer 9

5-flucytosine is converted, by cytosine deaminase, to its metabolically active form 5-fluorouracil (5-FU), which inhibits protein synthesis and inhibits thymidylate synthase hence inhibiting DNA synthesis.

Question 10

How is 5-Flucytosine commonly administered?

Answer 10

Oral (good oral bioavailability)

IV is available too

Question 11

State at least 2 adverse effects associated with the use of 5 flucytosine

Answer 11

1. Bone marrow suppression
2. Hepatotoxicity
3. GI related effects

Question 12

State one clinical indication for 5-flucytosine

Answer 12

1. Cryptococcal meningitis (usually in combination with amphotericin B, rarely used as single agent due to resistance)

Question 13

Name 3 echinocandins

Answer 13

1. Caspofungin
2. Micafungin
3. Anidulafungin

Question 14

State the mechanism of action of the echinocandins

Answer 14

Echinocandins inhibit the activity of the glucan synthase complex, resulting in loss of the structural integrity of the cell wall.

Question 15

How are echinocandins commonly administered?

Answer 15

Intravenously (poor oral bioavailability)

Question 16

Name 2 fungal species against which Echinocandins have potent activity

Answer 16

1. Candida

2. Aspergillus

Question 17

What is the mechanism of action of azoles?

Answer 17

They inhibit C-14 α-demethylase (CYP450 enzyme), thereby blocking the demethylation of lanosterol to ergosterol. This inhibition of ergosterol biosynthesis disrupts membrane structure and function and inhibits fungal cell growth.

Question 18

Do the triazoles have good oral bioavailability?

Answer 18

Yes

Question 19

State 3 adverse effects common to the triazoles

Answer 19

1. QT prolongation
2. Hepatotoxicity
3. GI side effects

Question 20

Name a triazole which is associated with the adverse effect of cardiotoxicity

Answer 20

Itraconazole

Question 21

Name a triazole which is associated with the adverse effect of neurotoxicity

Answer 21

Voriconazole

Question 22

Name one class of anti-fungals, which is significantly associated with CYP450 enzymes related drug-drug interactions?

Answer 22

Azoles
(Other non anti-fungal agents include macrolides, HIV protease inhibitors, rifampicin, which all have either significant CYP450 inhibitory or inducing activity) Antibiotics like fluoroquinolones and tetracyclines does have some DDI too)

Question 23

Which azole should not be taken with antacids?

Answer 23

Itraconazole (low pH improves absorption)

Question 24

Which azole is the treatment of choice for the management of aspergillosis?

Answer 24

Voriconazole

Question 25

How are the imidazoles commonly administered?

Answer 25

Topical (minimally absorbed)

Question 26

Name 2 anti-fungal drugs that can be used in the management of vuvlovaginal candidiasis and describe how it is administered

Answer 26

1. clotrimazole (cream)
2. fluconazole (single dose oral)
3. miconazole (vaginal suppository)
4. nystatin (vaginal suppository)

Question 27

Is nystatin administered parenterally?

Answer 27

No

Question 28

State a clinical indication for nystatin, and how it is administered.

Answer 28

1. oropharyngeal candidiasis (oral agent; swish and swallow or swish and spit)
2. vulvovaginal candidiasis (vaginal suppository)

Question 29

What is terbinafine’s mechanism of action?

Answer 29

It inhibits squalene epoxidase, thereby blocking its conversion to lanosterol and biosynthesis of ergosterol, an essential component of the fungal cell membrane.

Question 30

How is terbinafine administered for the management of tinea capitis?

Answer 30

Oral (Topical application cannot be used for the management of tinea capitis)

Question 31

Which of the following option(s) is/are least suited for a fungal meningeal infections?
A. Amphotericin B
B. 5-Flucytosine
C. Echinocandins
D. Fluconazole
E Itraconazole
F.Voriconazole

Answer 31

Echinocandins and Itraconazole have poor CSF penetration.

Question 32

What are some of the anti-fungal agents used in the treatment or onychomycosis?

Answer 32

Itraconazole - oral

Terbinafine - oral