Anti fungal Drugs

Question 1

What are the two categories in azoles?

Answer 1

Imidazole’s and triazoles.

Question 2

What are the imidazoles?

Answer 2

COMET-K azoles.

Question 3

What are the triazoles?

Answer 3

FIT VIP azoles.

Question 4

What are the azaleas mechanism of action?

Answer 4

They interfere with the synthesis of ergosterol, leading to defective cell membranes (lots of stress on membrane walls). They inhibit the enzyme responsible for converting lanosterol into ergosterol.

Question 5

What kind of infections do azoles treat?

Answer 5

Both local and systemic infections. Broad activity.

Question 6

What are the structural characteristics of azoles?

Answer 6

They are heterocyclic rings with nitrogens.

Question 7

Clotrimazole

Answer 7

Imidazole. Cream, ear drops, troche. Treats vaginal yeast infection, jock itch, thrush, ringworm, etc. Side effects are signs of common skin irritation.

Question 8

Ketoconazole

Answer 8

Shampoo, tablet, cream. Imidazole. Requires low pH for best absorption. Many dose-limiting side effects in oral form.

Question 9

FLuconazole

Answer 9

Triazole. Oral, IV, topical. Thrush in AIDS patients, Cryptococcus meningitis. Better tolerated than ketoconazole. Resistance common, but limited. Rash, nausea, hepatotoxicity.

Question 10

Itraconazole

Answer 10

Triazole. Better specificity for fungal CYp450, less toxic to people. Broader spectrum than fluconazole, but not as well tolerated. Drug of choice for non-threatening mycoses. Many potential side effects,

Question 11

What are the new azoles?

Answer 11

Voriconazole and Posaconazole are triazoles. They have good activity against broad spectrum, including aspergillus.

Question 12

What is a side effect of voriconazole?

Answer 12

Visual disturbances.

Question 13

What new azole is similar to itraconazole and has a better spectrum of activity? What is the drawback?

Answer 13

Posaconazole. It has serious side effects including diarrhea, nausea, fever, and increased liver enzymes.

Question 14

Can resistance develop in fungi? What has flourished especially?

Answer 14

Yes, especially in azoles due to widespread use of fluconazole. Candida has become resistant.

Question 15

What are three methods of azole resistance?

Answer 15

1. Target over expression (more ergosterol to combat antifungals)
2. Efflux pumps to pump out azoles.
3. Block my changing response of membrane

Question 16

Polyenes include what drugs?

Answer 16

NAN: “Polly want some nan?”
Natamycin
Amphotericin B
Nystatin

Question 17

What is the mechanism of action of polyenes?

Answer 17

“Polyenes make the cell go pee pee.” They bind to ergosterol to forms channels that cause cellular ions to leak out of the cell, ending with osmotic cellular lysis. Kills the cell.

Question 18

Amphotericin B

Answer 18

Characteristic structure with a large ring - double bonds on one side and multiple hydroxyls on the other. Highly nephrotoxic, 80% of patients will show kidney damage.

Question 19

What are the drugs in the echinocandins class?

Answer 19

MAC: “Old macdonald had a glucan and a fungin, EIEIO.” Structure looks like a funion with OH groups. Be careful, unions give you thrush (treat candida)
Micafungin
Anidulafungin
Caspofungin

Question 20

What is the mechanism of action of echinocandins?

Answer 20

They inhibit cell wall synthesis by blocking the glucan synthase. They are non-competitive inhibitors, and cause cell wall stress.

Question 21

Caspofungin

Answer 21

Invasive aspergillosis and Candida. Little side effects. Structure is circular, is lipophilic, and has many OH’s metabolized by acetylation. Not active against cryptococcus. Resistance is rare.

Question 22

Anidulafungin

Answer 22

Candidiasis, candidemia

Question 23

Micafungin

Answer 23

Candida, even azole-resistant candida.

Question 24

What does Flucytosine do?

Answer 24

It is a pyrimidine analogue used to target DNA/RNA synthesis - can have severe side effects. Usually combined with Amphotericin B due to resistance with mono therapy.

Question 25

What does Griseofulvin do?

Answer 25

“The Grinch doesn’t like to be separate from his dog.” It inhibits mitosis in dermatophytes (infection of hair and nails). Taken orally, ineffective topically. Prevents separation of chromosomes. Fungistatic.

Question 26

What drugs are in the allylamine group?

Answer 26

ANT: “Look, allyl ANT.”
Amorolfin
Naftifine
Terbinafine

Question 27

What is the mechanism of action of the allylamines?

Answer 27

They inhibit squalene epoxidase in the early ergosterol synthesis pathway. Usually used for nails, but can be topical or systemic.

Question 28

Butenafine

Answer 28

Better fungicidal activity that terbinafine. An allylamine.

Question 29

What is tolnaftate, and what is it used for?

Answer 29

It is a thiocarbamate, and it is used topically for athlete’s foot and jock itch. Not thrush. Also targets squalene epoxidase in the ergosterol synthesis pathway, which affects cell wall integrity.