Anti-Fungal Drugs Flashcards
What are three types of fungal infections?
Superficial skin
Superficial GI and GU (oral and vaginal)
Systemic (pneumonia, meningitis, UTI, septicemia)
Why is resistance increasing re anti-fungals?
Immunocompromised patients are living longer with chronic fungal infections
Antifungals are given to some patients as prophylaxis
What are two polyenes and what is their MoA?
Amphotericin B and Nystatin
MoA: Bind to ergosterol and form a pore causing leakage leading to fungicide
What are the adverse effects of Amphotericin B and how does this affect its indications?
It also binds with HOST cholesterol causing:
Infusion reactions: chills, fever, HA, Vomit, Hypotension (decreased if slow infusion + NSAIDS & antihistamines)
Long Term treatment leads to reversible then irreversible kidney damage.
Therefore, used only for life-threatening systemic infections.
Patient starts with AmphoB but then switches to safer azole.
Why is Amphotericin B given intrathecally for meningitis?
It is poorly absorbed and does not really cross the blood brain barrier.
Why is Nystatin only given topically as a cream, mouth rinse or suppository?
It is too toxic for parenteral
What is the MoA of the “azoles”?
Inhibit fungal cytochrome P450 (14 alpha sterol demethylase) leading to decreased ergosterol synthesis
What is the biggest down side to Azoles?
Drug Drug interactions because they also inhibit human P450s.
Otherwise they have few side effects.
What are the indications for Fluconazole?
Best penetration + highest therapeutic index (safest) of azoles
Drug of choice for:
cyrptococcal meningitis
prophylaxis for candida
Also Tx for candidemia and mucocutaneous candida
What are the adverse effects fo fluconazole?
Teratogenic
Stevens Johnson (but rare)
Inhibits CYP2C9 re phenytoin and warfarin
What are the indications for itraconazole?
Drug of choice for:
Dimorphic fungi: histoplasma, blastomyces, sporthrix
What are the adverse effects of Itraconazole?
It can cause CHF so contraindicated if ventricular dysfunction
Potent inhibitor of CYP34A re statins, medazolam
What are the indications for Voriconazole?
InVasive aspergillosis
Also: candida and dimorphic fungi
What are the adverse effects of voriconazole?
reversible Visual disturbances
(blurring, color, brightness x 30 mins)
What is the newest class of antifungals and how do they work?
Echinocandins such as Caspofungin
MoA: inhibit Beta 1-3 glucan synthase
to inhibit cell wall synthesis
What are the indications for Caspofungin?
Aspergillus and Candida only
(Aspergillis resistant to Voriconazole)
What are the adverse effects of Caspofungin?
Hepatotoxicity, especially with cyclosporine
GI discomfort, flushing
Embryotoxic
Drug drug re tacrolimus and rifampin
What is the MoA of Griseofulvin?
Mitotic inhibitor by disrupting microtibules
Keratophillic re NEW nail growth
so can take 6 mo to 1 year to work
What are the adverse effects of Griseofulvin?
Oral administration as microcrystalline form
S/E: CNS problems, serum sickness, hepatotoxic, GI problems
P450 inducer (like rifampin) so decreases efficacy of other meds
WHY would anyone take this drug just to fix their toenail fungus?
What is the MoA of terbinafine (Lamisil)?
Inhibits squaline epixidase (inhibits squaline from becoming squaline epoxide).
Increase in toxic squaline
Keratophilic and fungicidal
Oral x 3 mos (also comes topical)
What are the indications for terbinafine?
Dermatophytoses
Onychomycosis
What are the adverse effects of terbinafine?
Very few!
Some GI disturbance, headache
NO P450 or drug drug interactions
Your patient is 80 years old and on multiple medications.
He has a fungal infection of his toenails and also has ringworm. What would be a good medication for him?
Terbinafine because it treats dermatophytoses and onychomycosis and has not P450 interactions.
What is the MOA of Flucytosine?
Antimetabolite: Inhibition of DNA and RNA synthesis by fungal cells by blocking precursors.
Taken up by cytosine permease and converted to 5FU by cytosine deaminase by fungal cells only.
Is flucytosine broad or narrow spectrum?
How does this affect how it is used?
Narrow spectrum but has synergy with other meds:
Used with AmphoB for cryptococcus
Used with Itraconazole for chromoblastomycosis
So flucytosine is not converted into 5FU by human cells
so that eliminates its side effects right?
Nope. It can be converted into 5FU by our gut bacteria
especially in patients with renal insufficiency or AIDS
leading to serious hepatotoxicity and bone marrow suppression
What antifungal is okay for pregnant women?
Surprisingly: Amphotericin B
What is the big problem with azoles?
Inhibition of human P450s leading to drug drug interactions
Your patient has cryptococcal meningitis. What do you prescribe?
Fluconazole: best penetration of azoles
Your patient has aspergillus but did not respond to voriconazole. What do you try next?
Caspofungin
Your patient has histoplasmosis. What do you prescribe and what warning do you give your patient?
Itraconazole
Can cause CHF
