Antifungals Flashcards
Which antifungals target ergosterol?
Polyenes, triazoles and imidazoles.
Which antifungals inhibit ergosterol synthesis?
Allymines.
Which antifungals block the production of the beta-(1,3)-glucan protein damaging the cell wall?
B-3-glucan synthase inhibitors.
Which antifungals target chitin synthase?
Nikkomycin and polyoxin.
Which antifungals inhibit DNA/RNA synthesis?
Flucytosine.
Which antifungals inhibit fungal cell mitosis?
Griseofulvin.
List polyenes?
Nystatin.
Amphotericin B.
How is nystatin used?
Mostly topical and local treatment (oral thrush).
What is the effectiveness of absorption of nystatin?
Poor systemic absorption.
Poor oral bioavailability.
No drug interaction.
List MOA of amphotericin B?
binds to ergosterols to form pores, leading to leakage of molecules causing oxidative damage.
List the spectrum of activity of amphotericin B?
Candida, Aspergillus, Histoplasma, cryptococcus, and blastomyces.
What is the excretion method of polyenes?
Excreted by kidney slowly through months.
List the side effects of amphotecirin B?
Fever, chills, electrolyte abnormalities (hypokalemia), renal dysfunction, hematologic toxicity.
Give an example of fluorocytosine?
5-fluorocytosine.
List MOA of 5-fluorocytosine?
Inhibits thymidylate synthase and DNA synthase.
List spectrum of activity of 5-fluorocytosine?
Candida and crptococcus.
Resistance is common for which antifungal and how to fix it?
5-fluorocytosine.
List the adverse effects of 5-fluorocytosine?
Bone marrow toxicity - pancytopenia - reversible.
What is the mechanism of azoles?
Binds to ergosterol to form pores.
List the spectrum of activity of azoles?
Candida, aspergillus, histoplasma, cyptococcus, blastomyces, coccidiode, dermatophytes.
________ newer azoles with fewer side effects?
Triazoles.
Which antifungals work by inhibiting sterol 14 alpha- demethylase?
The azoles.
Adverse effects of the azoles are due to what?
Inhibition of mammalian steroid synthesis.
Drug interactions with azoles are due to what?
Inhibition of cyt.P450 enzymes.
Triazoles cause what?
Decrease potassium.
What is the MOA of echinocandins?
Inhibits 1,3-B-D-glucan synthase.
Echinocandins are used for what?
Aspergillosis and candidiasis.
What are echinocandins used for?
Empiric antifungal therapy.
What are the adverse effects of echinocandins?
Fever, histamine release, hypokalemia.
Give an example of echinocandins?
Capsofungin.
Echinocandins are metabolized by what?
Hydrolysis and N-acetylation.
Which antifungal is not an inhibitor/inducer/substrate of CYP?
Echinocandins.
List allylamines?
1- naftifine.
2- terbinafine.
3- butenafine.
List properties of naftifine?
- only available as gel or cream. (Poor systemic absorption 4-6%).
- no interactions found.
What are the substrates for terbinafine?
1A2, 2C9/19, 3A4.
_______ decreases terbinafine clearance by 33%
Cimetidine.
________ increases terbinfine clearance by 100%?
Rifampin.
What is the inhibitor of terbinafine?
2D6 strong.
Terbinafine Increases ________ leavels, ________ (Cmax up 1.9 folds), ________ (t1/2 up to 400 hours), __________ (Cmax up 2 folds)
Nortriptyline, paroxetine, amitriptyline, desipramine.
What is the inducer of terbinafine?
3A4 weak.
terbinafine increases metabolism of ________ by 15%?
Cyclosporine.
Which antifungal binds to microtubules/ disrupts mitosis?
Griseofulvin.
Griseofulvin deposits where?
In keratin layers.
__________ actively concentrate griseofulvin
Dermatophytes.
Griseofulvin is used for what?
Infections of the skin, hair, nails; prolonged therapy.
List toxicity of griseofulvin?
Headache, neuro and hepatotoxicity, photosensitivity, carcinogenic.
List topical antifungals?
1- tolnaftate.
2- nystatin.
3- naftifine.
4- terbinafine.
Topical antifungals are used for what?
Stratum corneum mucosa, cornea by dermatophytes and candida.
Topical antifungals are not used for what?
Subcutaneous, nail or hair infections.
Whitfields ointment contains what?
Benzoic + salicylic acid.
