Fungi Flashcards
What are the drug targets of anti-fungals?
Cell Wall: Echinocandins, chitlin synthetase inhibitors
Plasma Membrane: Polyenes and Azoles
DNA synthesis: Flucytosine
What are side effects of Ampho B?
Needs to be given IV
Significant infusion associated toxicity; fever, rigors, chills, hypotension and dyspnoea
Renal toxicity: decreased eGFR, hypokalaemia and hypomagnesemia
Need to use IV fluids before and after infusion
How does Ampho B work?
FungiCIDAL
has broadest anti-fungal capacity
Binds to fungal Membrane and alters permeability to K+ and Mg+
What are the benefits of L-AMB and ABLC?
ABLC and L-AMB have reduced side effects
L-AMB is particularly good for renal side effects
They are not more efficacious, they are safer!
How do Azoles work?
Act at plasma Membrane, inhibit synthesis of ergosterol by blocking demethylation of lanoesterol
What are diff azoles?
Ketoconazole: oral tablet, very significant liver toxicities
Itraconazole: Oral cap and solution, associated with fluid retention–heart and liver disease, pseudohyperaldosteronism , lots of drug interactions. Choice of drug for blasto, histo, sporo, non CNS Cocci
Fluconazole: Oral tab and solution, IV formula, has fewest drug interactions. Used for candida, crypto and CNS cocci
How do you treat each organism?
Candida– flu/itra/vori/Posa/Isavu (all effective)
Aspegillus– Itra/Vori/Posa/Isavu are effective (Fluconazole is not effective)
Cytococcus– Itra/Vori/Posa/Isavu (all effective)
Histo/Cocci/Blasto-Flu/Itra/Vori/Posa/Isavu (all effective)
Zygomycetes- Posaconazole and Isavuconazole only
What are SE of Voriconazole?
Visual disturbance
Mild hepatotoxicity
Skin Rash (including photosensitivity, assoc erythema and desquamation)
Drug interactions should be considered
What is voriconazole best for and worst for?
Best for Aspergillus
Worst for Zygomycetes
What is good about Posaconazole?
Once daily dosing
FungiCIDAL against Aspergillus and scedosporium
Highly active against Zygomycetes
Broadest anti-fungal
What is first choice for Candida?
Fluconazole for both invasive and candidemia
Voriconazole 2nd line
What is coccidioidomycosis treated with?
Non meningeal– Itra or flu
Meningeal–Fluconazole
What is crytpococcosis treated with?
Fluconazole for primary and maintenance
Voriconazole 2nd line
How do you treat aspergillosis?
Itraconazole, 2nd line Posa/Isavu
How do you treat blasto/histo/Parracoccy/Sporotrichosis?
Itraconazole
2nd line Posaconazole or voriconazole
What are echinocandins?
Anidulafungin
Caspofungin
Micafungin
How do echinocandins work?
Designed for candida, Aspergillus and penumocystis
Inhibit (1,3)-B-D-glucan syntahse which forms glucan polymers in cell Wall
What do they work against?
FungiCIDAL against Candida
Fungi static against Aspergillus
Intermediate activity against dimorphic fungi such as histo/blasto/coccidioides
What do echinocandins not work against?
Cryptococcus, fusarium, paecilomyces, trichosporan or Zygomycetes
How do you treat invasive candida?
Echinocandins
NOT for CNS candida
What is Flucytosine (5FC)?
Only available orally
Short half life, QDS dosing for normal eGFR
What are SEs of Flucytosine?
Mainly vomiting and diarrhoea
Deranged LFTs
Bone marrow suppression
What do you use Flucytosine for?
Candidiasis
Cryptococcal meningitis
What is Terbinafine?
Only used orally
Very broad spec cover
What is Terbinafine used to treat?
Very good activity against sporothrix schenckii
Onchomycosis
Tinea Capitis
Can be used to crytpococcal meningitis
