Anti fungal Drugs Flashcards
(29 cards)
What are the two categories in azoles?
Imidazole’s and triazoles.
What are the imidazoles?
COMET-K azoles.
What are the triazoles?
FIT VIP azoles.
What are the azaleas mechanism of action?
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.
What kind of infections do azoles treat?
Both local and systemic infections. Broad activity.
What are the structural characteristics of azoles?
They are heterocyclic rings with nitrogens.
Clotrimazole
Imidazole. Cream, ear drops, troche. Treats vaginal yeast infection, jock itch, thrush, ringworm, etc. Side effects are signs of common skin irritation.
Ketoconazole
Shampoo, tablet, cream. Imidazole. Requires low pH for best absorption. Many dose-limiting side effects in oral form.
FLuconazole
Triazole. Oral, IV, topical. Thrush in AIDS patients, Cryptococcus meningitis. Better tolerated than ketoconazole. Resistance common, but limited. Rash, nausea, hepatotoxicity.
Itraconazole
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,
What are the new azoles?
Voriconazole and Posaconazole are triazoles. They have good activity against broad spectrum, including aspergillus.
What is a side effect of voriconazole?
Visual disturbances.
What new azole is similar to itraconazole and has a better spectrum of activity? What is the drawback?
Posaconazole. It has serious side effects including diarrhea, nausea, fever, and increased liver enzymes.
Can resistance develop in fungi? What has flourished especially?
Yes, especially in azoles due to widespread use of fluconazole. Candida has become resistant.
What are three methods of azole resistance?
- Target over expression (more ergosterol to combat antifungals)
- Efflux pumps to pump out azoles.
- Block my changing response of membrane
Polyenes include what drugs?
NAN: “Polly want some nan?”
Natamycin
Amphotericin B
Nystatin
What is the mechanism of action of polyenes?
“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.
Amphotericin B
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.
What are the drugs in the echinocandins class?
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
What is the mechanism of action of echinocandins?
They inhibit cell wall synthesis by blocking the glucan synthase. They are non-competitive inhibitors, and cause cell wall stress.
Caspofungin
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.
Anidulafungin
Candidiasis, candidemia
Micafungin
Candida, even azole-resistant candida.
What does Flucytosine do?
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.
