Anti-fungals Flashcards
Amphotericin B - Mechanism
Binds ergosterol (unique fungi sterol) Forms pores/holes in membrane
Amphotericin B - Clinical Use
Systemic mycoses (Histo, Coccidio, Blasto)
Cryptococcus (with/without flucytosine)
Candida, Mucor
Amphotericin B - Toxicity
Fever/chills K and Mg loss (supplement) Hypotension Nephrotoxicity Arrythmias Anemia IV phlebitis
“FeHK MAAIN”
Hydration reduces toxicity
Liposomal amphotericin reduces toxicity
Nyastatin - Mechanism
Binds ergosterol (unique fungi sterol) Forms pores/holes in membrane
Nyastatin - Clinical Use
Topical use (diaper rash, vaginal candiadisis) Oral candidiasis (oral)
Azoles - Mechanism
Inhibit fungal sterol (ergosterol) synthesis by inhibiting P-450 enzyme unique to fungi that converts lanosterol to ergosterol
Build-up of lanosterol causes death of fungi
Azoles - Clinical Use
Azoles have a broad spectrum of antifungal activity, but most lack activity against mucor (posaconazole is an exception)
Superheroes (“Zod”) don’t have to wipe their nose
What do you use for chronic prophyaxis of cryptococcal meningitis in AIDS patients?
Fluconazole
What do you use itraconazole for mostly?
Histo, Coccidio, Blasto
Fluconazole or Itraconazole for local infection, Amphotericin B for systemic
What azoles can you use for topical infection?
Clotrimazole and miconazole
Azoles - toxicity
Testosterone synthesis inhibition (gynecomastia, esp. with ketoconazole) - all superheroes need testosterone, but Zod isn’t “man enough”
Liver dysfunction (inhibits cytochrome P-450) - elevated transaminases (recall mech.)
Prolonged QT (Smallville was stretched out way too long)
Flucytosine - mechanism
Inhibits RNA biosynthesis by conversion to 5-FU by fungal cytosine deaminase
Also inhibits DNA synthesis via another mech.
Flucytosine - Clinical Use
Used in systemic final infections (esp. meningitis caused by Crytococcus) in combination with Amph. B
Amphibian terminator shooting a toe from flute-gun at the crippled cock
Flucytosine - Toxicity
Bone marrow suppression (think DNA/RNA effects)
Rash
Diarrhea
Transaminases
Caspofungin, Micfungin - Mechanism
Inhibits 1,3 Beta D glucan synthase enzyme (present in all Asomycetes except B. dermatitis and very low levels in Cryptococcus; not present in Mucors or humans
Caspofungin, Micfungin - Clinical Use
Invasive aspergillus, Candida
Get gin in CANADA (no duty free)
Asperagus and gin don’t mix
Caspofungin, Micafungin - Toxicity
GI upset, flushing (via histamine release)
Drinking gin makes you feel warm
Terbinafine - Mechanism
Inhibits fungal enzyme squalene epoxidase
The squeling ox ran for its life when it saw a turbin on fire on its owner!
Terbinafine - Clinical use
Treat dermatophytes (tinea species - esp. onchomycosis, fungal infection of finger or toe nails)
The turbin was riddled with tinea capitis, causing a fiery itch (nails)
Terbinafine - Toxicity
Abnormal LFTs, visual disturbances
He got his turbin on fire because he was drinking too much alcohol (elevated LFTs) and therefore began having visual disturbances, which led to him setting himself on fire!
Griseofulvin - Mechanism
Interferes with microtubule function; disrupts mitosis. Deposits in keratin-containing tissues (e.g. nails)
Grizzly has a lot of hair (deposits in keratin) - it hibernates in the winter (interferes with motility - microtubules).
Griseofulvin - Clinical Use
Oral treatment of superficial fungal infections; inhibits growth of dermatophytes (tinea, ringworm)
Grizzly needs protecting for all its hair!
Griseofulvin - Toxicity
Teratogenic, Carcinogenic, Confusion, Headaches, Increased P450 and warfarin metabolism
Don’t wake up Grizzly from her hibernation with the P450 rocket and war-rifle! She’ll become confused not knowing what season it is and get a headache from waking up too suddenly.
If you do wake up the bear…
A giant tarantula (teratogenic) will appear in its car (Carcinogenic) to…
