Antifungals

Question 1

Which groups of antifungals have an action that inhibits membrane synthesis?

Answer 1

Azoles

Echinocandins (Caspofungin)

Question 2

Which groups of antifungals have an action that inhibits membrane function?

Answer 2

Polyenes

Allylamines

Question 3

Which groups of antifungals have an action that inhibit nucleic acid synthesis and mitosis?

Answer 3

Others - Flucytosine, Griseofulvin

Question 4

What is the mechianism of action of Azoles?

Answer 4

Inhibit 14-alpha-demethylase (cytochrome p-450 enzyme) which is responsible for producing ergosterol

=> ergosterol deplete => inhibit membrane formation

Th. fungi is killed by:

• inhibition of growth (inhibition of membrane formation)
• increased permeability of membrane
• accumulation of toxic sterol intermediates in cell

Question 5

Describe the interactions of Azoles with other drugs

Answer 5

Many drug interactions due to varying effects on human p450 enzymes

Question 6

What are the two classes of Azoles?

Answer 6

Imidazoles

Triazoles

Question 7

When are imidazoles used?

Answer 7

Only in topical treatment because of its toxicity

• treatment of candida
• treatment of tinea

Question 8

Give examples of Imidazoles

Answer 8

Ketoconazole
Miconazole
Clotrimazole (an active ingredient in Canesten)

Question 9

Give examples of Triazoles

Answer 9

Fluconazole
itraconazole
Voriconazole

Question 10

What can Fluconazole be used against?

Answer 10

Candida, Cryptococcus, Dermatophytes

- Candida krusei often resistant

Question 11

Fluconazole can be administered in which ways?

Answer 11

Topical
Oral - well absorbed from GIT
Rarely IV

Question 12

Why does fluconazole give good systemic availability?

Answer 12

Penetrates CSF

Excreted unchanged by kidney

Question 13

What can Voriconazole be used against?

Answer 13

Life-threatening Candida

Aspergillus infection

Question 14

Voriconazole can be administered in which ways?

Answer 14

Oral

IV - avoid in renal impairment

Question 15

What can Itraconazole be used against?

Answer 15

Candida
Aspergillus
Cryptococcus

Question 16

Itraconazole can be administered in which ways?

Answer 16

Oral - varying availability

IV

Question 17

Name two side effects specific to Itraconazole

Answer 17

Negative ionotrope => decreased muscle contractions

Liver damage and drug interactions

Question 18

Name a side effect specific to Voriconazole

Answer 18

Visual impairment

Question 19

What is the mechanism of Echinocandins, specifically Caspofungin?

Answer 19

Glucan synthase inhibitors

Caspofungin = weakens cell wall via inhibiting beta-glucan synthase

Question 20

What can Caspofungin be used against?

Answer 20

Aspergillus

Candida

Question 21

In which ways can Caspofungin be administered?

Answer 21

IV only

• must start with loading dose
• caution in hepatic impairment

Question 22

What is the mode of action of Allylamines?

Answer 22

Inhibits ergosterol synthesis by inhibiting the enzyme squalene epoxidase
- Th. inhibits membrane synthesis

Question 23

Give examples of Allylamines

Answer 23

Naftifine

Terbinafine

Question 24

What is Terbinafine used for?

Answer 24

Superficial dermaphyte infections

- administerd topical or oral

Question 25

What is the mode of action of Polyenes?

Answer 25

Increase membrane permeability by binding to Ergosterol | - Th. pore foormation and leakage of cations

Question 26

Give examples of Polyenes

Answer 26

Amphotericin Nystatin

Question 27

What is Amphotericin active against?

Answer 27

Systemic Aspergillus Candida Cryptococcus

Question 28

How can amphotericin be administered?

Answer 28

IV or intrathecally only - negligible GI absorption - high bound protein in blood

Question 29

Why may amphotericin cause hypokalaemia?

Answer 29

Due to renal toxicity effects

Question 30

What is nystatin used against?

Answer 30

Superficial candidiasis - topical only - nappy rash, thrush

Question 31

What is the mode of action of Flucytosine?

Answer 31

Inhibits DNA synthesis by inhibiting enzymes needed to produce thymidlyic acid (req. for DNA synthesis)

Question 32

Why must Flucytosine only be used in combination with Amphotericin?

Answer 32

Since resistance regularly occurs

Question 33

What is the mode of action of Griseofulvin?

Answer 33

Inhibits fungal mitosis | - used for dermatophyte infections

Question 34

What treatment would be used to treat vulvovaginal candidiasis?

Answer 34

Clotrimazole | alternative: Fluconazole

Question 35

What treatment would be used to treat fungal nail infection?

Answer 35

Terbinafine

Question 36

What treatment would be used to treat oral candidiasis?

Answer 36

Nystatin oral susension | Fluconazole = 2nd line

Question 37

What treatment would be used to treat tinea pedis (athletes foot)?

Answer 37

Clotrimazole 1% cream

Question 38

What treatment would be used to treat candidaemia (non-CNS)?

Answer 38

Fluconazole - oral | AmBisome = 2nd line

Question 39

What treatment would be used to treat aspergillosis (non-CNS)?

Answer 39

Voriconazole IV | AmBisome = 2nd line