Antifungals Flashcards
unique targets for antifungal therapy
fungal cell membrane - ergosterole and ergosterol synthesis
fungal cell wall - glucans
shared targets for antifungals
DNA/RNA synthesis
cell division
which drugs site of action is membrane function
amphotericin B
which drugs site of action is ergosterol syntheiss
Fluconazole Itraconazole Voriconazole Naftifine Terbinafine
which drugs site of action is nucleic acid synthesis
5-fluurocytosine
which drugs site of action is cell wall synthesis
caspofungin
systemically active drugs for systemic infections
- oral or IV use
Polyenes - amphotericin B**drug of choice or alternative
Azoles - most of them
Flucytosine
Echinocandins
what drug has the broadest spectrum activity of all antifungals
amphotericin B
MOA of amphotericin B
binds to ergosterol in fungal CM
forms amp B containing pores - altering permiability
fungicidal
how does resistance develop to amphotericin B
membrane ergosterol concentration is decreased
sterol target is modified
(Candida and Aspergillus)
Adverse effects of amphotericin B
**Nephrotoxicity (most common and most serious long term toxicity)
infusion related rxns - fever, chills, muscle spasms, vomiting, HA, hyper-/hypotension
how can amphotericin b be made less toxic
liposomal packaged formulations - decrease binding to human CM
MOA of azoles
bind to enzyme responsible for converteing lanosterol to ergosterol –>”leaky” cell membrane
SE of azoles
relatively non-toxic
minor GI
interaction with P450
Azole:
Frist oral azole
higher degree of inhibition of cytochrome p450
lower selective toxicity
largemely replaced by newer azoles
ketoconazole
highest therapeutic index of all azoles
lowest level of interaction with p450
fluconazole
Fluconazole is the agent of choice for treating what
candidiasis
cryptococcosis
coccidiomycosis
2nd line for other systemic infections: histoplasmosis, blastomycosis, sporotichosis
what drug has a broader spectrum of activity that fluconazole but poorer pharmacology and TI
Itraconazole
what does intraconazole require for absorption
low gastric pH
does itraconazole or fluconazole penetrate the CNS
fluconazole
what does itraconazole interact with
hepatic microsomal enzymes - significant interaction with commonly used drugs
what is itraconazole drug of choice for treating
- blastomycosis
- coccidiomycosis
- histoplasmosis
- sporotrichosis
- dermatophyte (onychomycosis)
due to its lower toxicity, what drug has replaced amphotericin B as tx of chioce for asperigillosis
vorconazole
spectrum of activity for voriconazole
Candida
Endemic dimorphic fungi
aspergillosis (tx of choice)
SE of voriconazole
- visual disturbances
- hallucinations
- liver enzyme abnormaliies
- rash
*similar to other azoles inhibits cytochrome p450
what has the broadest spectrum of activity of all azoles
Posaconazole
what does posaconazol treat
Candida
Aspergillus
Mucormycoses
Newer alternative therapy for invasive aspergillosis and mucromycosis
increased sollubility compared to voriconazole and posaconazole
less risk of nephrotoxicity
good bioavailability and T1/2
Isavuconazole
what is flucytosine used for
combo therapy for systemic infections:
cryptococcus
MOA of flucytosine
interferes with protein and nucleic acid synthesis
Flucytosine is distriubted throughout body fluids and tissues including the CNS. It can treat _____
cryptococcal meningitis
SE of flucytosine
bone marrow toxicity - anemia, leukopenia, thrombocytopenia
Lipopeptides that inhibit the synthesis of beta glucans of fungal cell walls
high degreee of selectivity towards fungal cells
administered IV
poor penetration of CNS
echinocandins (caspofungin, micafungin, anidulafungin)
spectrum of activity/tx of echinocandins
- limited to fungi with high levels of beta glucan
invasive infections caused by Candida and Aspergillus - primarily to tx infections that do not respond to other antifungal agents
oral systemic drugs for cutaneous and mucocutaneous infections
Griseofulvin
Allylamines - terbinafine
what drug is used to treat dermatophyte infections (2nd line)
concentrates in keratin precursor cells
Griseofulvin
drug interaction with griseofulvin
increase warfarin metabolism
decrease effectiveness of oral contraceptivs
MOA of allylamines
inhibit ergosterol syntehsis - inhibit enzyme squalene epoxidase
first line drug in the treatment of onychomycosis
keratophilic
oral terbinafine
what is the first TOPICAL triazole used to treat onychomycosis
low affinity for keratin - better penetration of nail bed
minimal systemic absorption
Efinaconazole
what are the topical antifungals
Polyenes - nystatin
Azoles - clotrimazole, miconazole
Allylamines - terbinafine, naftifine
polyene antifungal drug related to amphotericin B that is only used topically
active against most species of Candida
most commonly used in local infections - oropharyngeal and vaginal candidiasis
Nystatin
two most commonly used topical azoles (used for vulvovaginal candidiasis and dermatophytes infections)
oral lozneges are available for oral thrush
clotrimazole and miconazole
Drug of choice for asperigillosis
Voriconazole
alternative: posaconazole, amphotericin B, echinocandin
drug of choice to mild/moderate blastomycosis
intraconazole
alternative: fluconazole
drug of choice for moderate to severe blastomycosis
amphotericin followed by itraconazole
drug of choice for vaginal candidiassi
- intravaginal azole: clotrimazole, miconazole
or
intravaginal nystatin
or
fluconazole (oral)
drug of choice for oropharyngeal candidiasis
clotrinmazole or miconazole lozenges
nystatin
fluconazole
drug of choice for esophageal candidiasis
fluconazole
drug of choice for invasive candidiasis or blood stream
fluconazole
echinocandin
drug of choice for coccidiomycosis
fluconazole or itraconazole
