Antifungals Flashcards
Two names of polyenes
Nystatin ( topical)
Amphotericin
MOA of these drugs is to bind ergosterol in fungal cell membrane leading to cell death
Polyenes
Which candidia species is not sensitive to amB
C. lusitaniae ( lusitaniae sinks amB like the boat)
Other formulations of AmB .. Which one has the least Nephrotoxicity and infusion rxn
Liposomal Amphotericin b ) LAmB
The amp b colloidal dispersion is the worst and worst than the conventional AmB . The lipid complex is ok but lamb is better
This Azoles is used for onychomycosis
Itraconazole
Amphotericin toxicities and pk and pd
(Bind ergosterols in cell wall)
SE: Nephrotoxicity
Electrolyte wasting
Infusion related reactions
- poorly absorbed that’s why given IV , high distribution ( low in CNS) , concentration dependent
Inhibit fungal cytochrome p450 decreasing ergosterol formation
Azoles
What is the spectrum for amp b
Candidia, cryptococcus neoformans , dimorphic fungi and many molds
This Azoles doesn’t work against molds
Fluconazole
Inhibit beta 1,3-glucan synthase
Echinocandins
Azoles effective against ASPERGILLUS
Itraconazole , voriconazole
What is flu console ineffective against
C. Glabrata, c. Krusei, ( glide and cruise past fluconazole) aspergillus and molds
What is the big issue with Azoles
Drug interactions
What Azoles can you use for fungal UTIs
Fluconazole - excreted renally
Adverse reactions with Azoles
Hepatoxicity , rash and drug interactions
This Azole can be used to treat aspergillus, dematiaceous molds and dimorphic fungi
Itraconazole
Name the 5 major Azoles
Fluconazole, itraconazole,voriconazole , posaconazole, ketoconazole
Azoles are fungicidal to what and fungi static to
Fungicidal to molds and fungistatic to yeast . They are time dependent
This azole is used for invasive aspergillosis, invasive candidiasis, esophageal candidiasis and febrile neutropenia
Voriconazole
This drugs SE are visual effects ( purple fringe on stuff, wiggly lines) to hepatotoxicity to visual hallucinations
Voriconazole
This drugs main activity is against dermatophytes
Terbinafine
Safe for use in pts with renal issues
Echinocandins ( caspofungin, micafungin, anidulafungin)
Used in the treatment of candidiasis and prophylaxis but not c. kruseii and c. glabrata
Fluconazole
What’s the spectrum of the echinocandins
Candida but weak against C. parapsilosis
Active against ASPERGILLUS
Ineffective again CRYPTOCOCCUS and many molds
Fungicidal vs yeasts and pseudo static vs molds ( makes weird balls that don’t reproduce but don’t die either )
This azole was only approved for prophylaxis of fungal infections
Posaconazole
Interesting facts about posaconazole
Must be eaten with high fat meal or acidic beverage . ( new IV and oral tablets just approved so won’t use the suspension form anymore)
Yeasts including candidia and cryptococcus
Molds including aspergillus and zygomycetes
Number 1 treatment for candida if susceptible
Fluconazole
This drug inhibits squalene epoxidase preventing synthesis of ergosterol
Terbinafine
Pharmokinetics and adverse effects of echinocandins
IV only - poor bioavailability
No CNS distribution
Not really eliminated
Concentration dependent
SE - very well tolerated rxns are rare
Hepatotoxicity , infusion related rxn ( red man syndrome ) and phlebitis if given peripherally so give centrally.
Ketoconazole
Poor oral absorption, used topically , occasionally orally. Don’t use systemically
Name the antimetabolite
5-flucytosine (5-FC)
What is C. glabrata susceptible to
Flucytosine, and candins and kinda to AmB
What is C. kruseii resistant or kinda resistant to
fluconazole itraconazole , 5-FC and can be resistant to AmB
These drugs are used in combo therapy for cryptococcal meningitis
AmB and 5-FC
This drug concentrates in the nails ,fat and skin
Terbinafine
Where is terbinafine metabolized and excreted
40% bioavailable bc if 1st pass effect .
Metabolized in liver but metabolites are excreted renally . Non linear elimination half life goes from 12 hrs to 200 hours after repeated dosing
Terbinafines SE
Hepatotoxicity, neutropenia, Stevens-Johnson syndrome
Inhibits fungal mitosis via interaction with microtubules
Griseofulvin
All you need to know about griseofulvin
Used for dermatophytes BUT never use because headaches are very common
What is c. lusitaniae resistant to
AmB
What are the adverse effects of 5-FC
Bone marrow suppression - dose related
GI intolerance, rash, hepatotoxicity
Used in onychomycosis
Terbinafine
This azole has the worst side effects and Can cause heart failure, qt prolongation and the absorption is so bad you never really know if it was absorbed or not .
Itraconazole
This is the number one treatment for aspergillus
Voriconazole
Caspofungin , micafungin, anidulafungin
Echinocandins .. All work equally
What is the big issue with voriconazole a pk
It’s non- linear and there is a disproportional increase in concentration with increase in dose so be careful . It has a high intra and inter patient variability so might need to check the trough levels
