Antifungal Drugs Flashcards
What fungi are superficial?
Dermatophytes
Malassezia furfur
What fungi are subcutaneous?
Sporothrix schenckii
Basidiobolus ranierum
What fungi are primary systemic?
Histoplamsa capsulatum
Blastomyces dermatitidis
Coccidioides immits
Paracoccidiodes brasiliensis
What fungi are primary opportunistic?
Candida albicans Cryptococcus neoformans Aspergillus fumigatus Mucor/Rhizopus Pneumocystis jirovecii
What are the possible structures in a fungus that a drug could target?
Cell membrane (ergosterol) Cell wall (chitin, glucan, mannan) Nucleus Vacuole Cytoplasm Mitochondria
What antifungal inhibit cell wall (glucan) synth?
Echinocandins
What antifungals inhibit cell membrane (ergosterol) synth?
Polyene
Azoles
What antifungals RNA/DNA synth by the pyrimidine sythesis?
Flucytosine
What are the characteristics of the optimal antifungal?
Wide spectrum of activity Favorable bioactivity Adequate in vivo efficacy High therapeutic index Low cost
What are the polyenes?
Amphotericin B and Nystatin
What is the action of polyenes against fungi?
Binds to ergosterol to form a pore making the membrane leaky
Describe the structure of a polyene.
A large lactone ring with conjugated double bond with a lipophillic side and a hydrophillic side
What is amphotericin B produced by?
Streptomyces nodosus
In the cell membrane, what does amphotericin cause to happen?
Causes a leakage of NA+, K+ and Ca+2
Is amphotericin B a broad spectrum fungicidal?
Yes
How would you administer amphotericin B to a pt?
Intravenous ONLY
Why doesn’t amphotericin B work well in oral form?
It’s highly unstable in the GI and wants to be bound to serum proteins so it works better in the blood
Lipsomal amp-B exists for oral but its expensive
What adverse effects could amp-B have?
Binds to host cell of cholesterol causing the affinity to lessen and becoming toxic
The injection might hurt
Could cause acute chills, fever and vomiting
Could chronically cause nephrotoxicity
What is nystatin produced by?
Streptomyces noursei
Which polyenes are used for a local infection and which is used for severe fungal infections?
Nyastin for local
Amp-b for severe
How should nystatin be administered?
Topical cream or as a mouth wash (oral thrush)
How is an azole composed?
5-membered azole ring with at least one non-carbon atom
Classified by the number of nitrogen
Are azoles broad spectrum antifungals?
Yes
What is the mechanism for azoles?
Inhibits ergosterol synthesis by inhibition of CYP450
What could happen if an azole interacts with a human CYP450?
Drug detox could be impaired
Steroid hormone biosynth in adrenal gland could be impaired
What would you call an azole with two nitrogens? And what are some examples?
Imidazole
Ketoconazole and Miconazole
What would an azole be called if it had 3 nitrogens? And what are some examples?
Triazole
Itraconazole, Fluconazole, Clotrimazole and Voriconazole
What azole is effective against candida?
Voriconazole
What are the properties of Ketoconazole (KCZ)?
Broad spectrum
PO administration
Mostly replaced by fluconazole
What are the side effects of Ketoconazole?
Gynocomastia and hepatic failure
What are the properties of Miconazole?
Topical and vaginal suppositories
Dermatophytes
What are the properties of Clotrimazole?
Topical and vaginal suppositories
What are the properties of Fluconazole (FCZ)?
Oral, esophageal and vaginal candidas
Generally used post initial treatment with amp-b
Used for cryptococcal meningitis
Oral and IV
What are the properties of Itraconazole (ICZ)?
Broad spectrum inclusing tinea unguium
Indicated for systemic fungal infections
Also for oral and esophageal candidiasis
What are the properties of Voriconazole (VCZ)?
Oral and IV
High bioavailability
Indicated for invasive aspergillosis
Azole have very excellent _____ penetration.
CSF
What is the action of allylamine?
Inhibit squalene expoidase to dec erogsterol synthesis
What type of fungal infections do allylamines work against?
Superficial
How are allylamines administered?
Oral and topical
How do flucytosines work?
Blocks DNA and RNA synth
How are flucyosines adminstered and where do they penetrate the best?
Oral, CSF
What are flucyosines used against?
Candida and Cryptococcus neoformans
What is the mechanism of actions for flucyosines?
Cyostine specific permases
Converted to 5Fdump to distrucpt DNA
Converted to 5FUMP to disrupt RNA
What are echinocandins (caspofungin) produced from?
Glarea lozoyensis
How do you administer echinocandins?
IV
What is the mechanism of action for echinocandin?
Inhibits 1,3-B-glucan synthase
Cell wall synth inhibitor
What are echinocandins used for?
Invasive amp-B resistant aspergillosis
Esophageal candidiasis
Pneumocystis pneumonia
What is grieofulvin isolated from?
Pencillium griseofulvum
How does grieofulvin work?
Binds to fungal tubulin which interferes with microtubular function
What is grieofulvin highly effective against?
Athlete’s foot and other taenia infections
What are the side effects of grieofulvin?
Teratogenic and inc CYP450 metabolism
