Anti-fungal Agent

Question 1

Name 2 polyenes antifungal

Answer 1

1. Amphotericin B
2. Nystatin

Question 2

What is the mechanism of action polyene antifungals?

Answer 2

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 3

Name the 2 categories of azole antifungals

Answer 3

1. Triazole
2. Imidazole

Question 4

How is amphotericin B commonly administered?

Answer 4

IV (poor oral bioavailability)

Question 5

State 2 adverse effects associated with amphotericin B deoxycholate formulation

Answer 5

1.Fever and chills
2. Nephrotoxicity

Question 6

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

Answer 6

Liposomal formulation has reduced renal toxicity. However, liposomal formulation of amphotericin B is very expensive

Question 7

Name 2 clinical indications for amphotericin B

Answer 7

1. Candidiasis
2. Aspergilliosis

Question 8

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

Answer 8

Amphotericin B

Question 9

Name 2 echinocandins

Answer 9

1. Micafungin
2. Anidulafungin

Question 10

State the mechanism of action of the echinocandins

Answer 10

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

Question 11

How are echinocandins commonly administered?

Answer 11

Intravenously

Question 12

Name 2 fungal species against which Echinocandins have potent activity

Answer 12

invasive Candida (first line)
invasive Aspergillus (second line if amphotericin B or an azole is inappropriate)

Question 13

What is the mechanism of action of azoles?

Answer 13

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 14

What are the two different classes of azoles?

Answer 14

Imidazole and triazoles

Question 15

Do the triazoles have good oral bioavailability?

Answer 15

Yes

Question 16

State 3 adverse effects common to the triazoles

Answer 16

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

Question 17

What are the subcutaneous and systemic classes of antifungals?

Answer 17

Amphotericin B
Echinocandins
Triazoles

Question 18

What are the cutaneous classes of antifungals?

Answer 18

Imidazoles
Nystatin
Terbinafine

Question 19

What must be noted when prescribing azoles?

Answer 19

All azoles inhibit hepatic CYP450 3A4 isoenzyme. decreased metabolism of drugs like warfarin, cyclosporine and oral hypoglycemic agents

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

Which triazoles have excellent CSF penetrations?

Answer 22

Fluconazole and voriconazole

Question 23

Which triazoles should be taken after a full meal of chicken and coke?

Answer 23

Posaconazole (Oral bioavailability increased with high fat meal), chicken rice ( high fats);

itraconazole –> acidic environment increase bioavailability. coke (acidity)

Question 24

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

Answer 24

Voriconazole

Question 25

How are the imidazoles commonly administered?

Answer 25

Topical (minimally absorbed)

Question 26

What are the adverse effect of imidazoles?

Answer 26

Contact dermatitis

Question 27

What are the different types of imidazoles?

Answer 27

Clotrimazole
Miconazole

Question 28

What is the mechanism of action of nystatin?

Answer 28

v similar to amphotericin B; 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 29

Is nystatin administered parenterally?

Answer 29

No, topically or orally

Question 30

State 2 clinical indications for nystatin, and how it is administered.

Answer 30

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

Question 31

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

Answer 31

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

Question 32

What is terbinafine’s mechanism of action?

Answer 32

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

Question 33

How is terbinafine administered for the management of tinea capitis (infection of the scalp) / dermatophyte onychomycoses (fungal infections of nails)?

Answer 33

Oral (to build up its concentration in keratin)

Question 34

Which of the 3 cutaneous classes of antifungals can be given orally?

Answer 34

terbinafine