antifungals Flashcards
3 groups of fungal infections
-Systemic mycoses
-Subcutaneous mycoses
-Superficial mycoses
-think about where the pt was- did they travel -> broader spectrum antifungals
systemic mycoses
-Includes soft tissue infections, UTI, pneumonia, meningitis or septicemia
-Causative pathogens include Aspergillus, Blastomyces, Candida, Coccidiodes, Cryptococcus and Histoplasma
-Some infx – geographical, can occur in immunocompetent or immunocompromised
-Other infx – more likely to occur in immunocompromised or debilitated pts only
subcutaneous mycoses
-Caused by puncture wounds contaminated with soil fungi
-Infx include chromomycosis, scedosporium and sporotrichosis
superficial mycoses
-Infx of nails, skin and mucous membranes usually caused by dermatophytes or yeasts
-Dermatophytes – Epidermophyton, Microsporum, Trichophyton. Dermatophyte infx include tinea pedis (athletes foot), tinea capitis or corporis (ringworm) and tinea cruris (jock itch)
-Yeasts – Candida albicans and non-albican species species (ex Malassezia furfur)
-Candida infx include thrush, vaginal infx and diaper rash
-Malassezia furfur infection – Tinea Versicolor. Primarily treated with selenium sulfide shampoo
classification of antifungals: polyene class
-amphotericin
-natamycin
-nystatin
classification of antifungals: azole derivatives
-miconazole
-clotrimazole
-econazole
-fluconazole
-itraconazole
-ketoconazole
-voriconazole,
-posaconazole
classification of antifungals: allylamine drugs
-naftifine
-terbinafine
-butenafine
classification of antifungal drugs: echinocandin class
-capsofungin
-micafungin
-anidulafungin
antifungals: miscellaneous
-ciclopirox
-flucytosine
-griseofulvin
-tolnaftate
amphotericin B
-Fungizone, Amphotec, Ambisone, Abelcet (last three are lipid form)
-Available IV*, Fungizone also available topical
-Not absorbed PO
-MOA- binds to ergosterol in fungal cell membrane and increase cell membrane permeability
-Indications: Broad spectrum antifungal. Used for !systemic infections! due to aspergillus, blastomyces, candida, coccidiodes, cryptococcus and histoplasma (the bad ones)
-Liposomal amphotericin B or Lipid Complex amphotericin B + Flucytosine PO used for cryptococcal meningitis induction phase
-must give VERY slow and HYDRATE
amphotericin B ADRs and cons
-amphoterible
-chills, fever, vomiting, H/A , renal and hepatic impairment, anemia, hypokalemia, hypomagnesaemia, hypotension, phlebitis
-lipid formulations have less ADRs
-High cost, difficulty of administration (solubility and stability factors with IV use) and side-effect profile don’t make it the first line drug
-Most often given in combination with other antifungals to reduce toxicity
cultures
-fungal infection- takes 2 weeks to swab
-bacteria- 24-48 hrs
-if bacteria comes back neg we assume fungus
nystatin
-nycolog, mycostatin
-available in topical form only - apply to skin, oral or vaginal mucosa for Candida infections
-powder, suspension (for oral)
-needs to be applied multiple times a day in a thin layer
-One of the preferred agents for treatment of superficial candidal infections
-swish and spit usually, if down the throat -> swish and swallow
natamycin
-natasyn
-ophthalmic suspension for TX of fungal blepharitis, conjunctivitis or keratitits caused by Aspergillus sp. and Candida sp.
azole derivatives
-MOA - inhibits synthesis of fungal lipid ergosterol
-Spectrum - Active against a wide range of fungi including dermatophytes and yeasts
-Indications - Topical for superficial infx, orally for more severe superficial infx as well as for subcutaneous and systemic infx and IV for systemic infections
-Kinetics - Well absorbed PO, some require acidic medium for absorption
-clotrimazole
-econazole
-fluconazole
-ketoconazole
-itraconazole
-miconazole
-posaconazole
-voriconazole
clotrimazole
-topical
-too toxic for systemic use. (Available as cream, vaginal tablets, troches)
-effective for oral, topical or vaginal candidiasis & some forms of tinea
econazole
-topical
-used topically for tinea and candidal infections
-can be used once daily- good!
fluconazole
-diflucan
-PO, IV
-Used to Tx candida (oral, esophageal and systemic) and cryptococcal meningitis b/c it crosses BBB.
-Used for prophylaxis of fungal infections in patients undergoing bone marrow transplant
-Also given as single oral dose for recurrent vaginal candidiasis
-pts that get yeast infections with antibiotics -> prophylaxis with this
ketoconazole
-PO and topical
-Used for a variety of systemic fungal infections but does not enter the CNS in significant concentrations.
-Has anti-androgenic properties, so has other indications
-Requires acidic medium to be absorbed- orange juice, stomach acid (empty stomach)
-seborrheic dermatitis
-anti hair loss- anti-androgenic-DHEA
-endocrine effects like gynecomastia w/ ketoconazole (androgen blocker)
-decrease libido, ED for men
-menstrual irregularities for women
-can affect BC
itraconazole
-PO, IV
-active vs. a wide variety of fungi (especially resistant species)
-Preferred treatment for blastomycosis, sporotrichosis, and histoplasmosis
miconazole
-monistat
-topical
-Too toxic for systemic use
-Used vaginally or topically for candida and tinea.
-One of MC agents used for vaginal yeast infections
-do not reuse applicators
posaconazole
-noxafil
-PO
-!!newest azole antifungal for the prophylaxis of Aspergillus and Candida in severely immunocompromised patients
-cover more strands of candida
-ONLY ORAL- limits it
-Must be administered with a full meal or nutritional supplement!!! -> limits it bc need pt to be NG tube fed (not IV feed)
voriconazole
-PO, IV
-2nd generation triazole with improved antifungal activity against Aspergillus fusarium species and fluconazole-resistant candida
-can give IV for emergency and dont need empty stomach
-Lots of CYP450 DDIs
-visual disturbances with voriconazole- hallucinations, rashes
azole ADRs and DDIs
-ADRs – 2 MC ADRs are hepatotoxicity and GI effects
-unique ADRs amongst different azoles
-endocrine effects like gynecomastia w/ ketoconazole (androgen blocker)
-visual disturbances with voriconazole- hallucinations, rashes
-DDIs
-Inhibits cytochrome P-450 system: caution with CYP450 substrates like phenytoin, warfarin, hypoglycemics (to name a few)
-Decreased absorption of azole (mostly w/ ketoconazole and itraconazole) w/ drugs that decrease gastric acidity (antacids, H2 blockers, PPIs)
allyamines and ADRs
-MOA – inhibit ergosterol synthesis
-Examples:
-Terbinafine – PO, topical
-Indications: Can be used to treat dermatophytoses
-6-12 weeks of PO therapy is the preferred tx for fungal nail infections!!!!!!!!!!!!
-ADRs: GI, headache, rash. LIVER toxicity, rare but serious!!!! -> no alcohol, careful with statins
-Naftifine – topical
-Tx of jock itch, ringworm and athletes foot
-Butenafine– topical
-Tx of jock itch, ringworm and athletes foot
echinocandin class
-Newest class of antifungal agents (IV only) -> limits
-MOA - inhibit fungal cell wall synthesis
-Very good activity against candida and aspergillus
-ADRs – histamine like reactions (facial flushing, rash, fever, pruritis)
-great for candida (fungicidal) and good for aspergillus (fungistatic)
-Examples:
-capsofungin (Cancidas) & micafungin (Mycamine)
-Newest agent in this class - anidulafungin (Eraxis)
-aspergillus tx with fungin (IV) and azole (PO) is great
fungicidal vs fungistatic
-fungicidal kill fungus
-fungistatic keeps it at bay
other: flucytosine
-ancoban
-PO
-MOA: inhibits DNA synthesis as a result of its conversion to 5-fluorouracil.
-Indications: Limited usefulness as a single agent because resistant strains emerge very quickly
-Most often used in combination with amphotericin for tx of systemic candida or cryptococcus
-Prolonged high doses may suppress bone marrow and cause alopecia (5-FU effect).
-ADRs: bone marrow suppression, hepatic dysfunction
other: griseofluvin
-fulvicin
-PO
-Used for dermatophytes (epidermophyton, trichophyton)
-tx of choice for tinea capitis
-Must be taken with high fat foods to maximize absorption!
-Rarely used today because other agents work faster and more efficiently and with less ADRs.
-ADRs include fever, rashes, leukopenia, N,V,D, hepatotoxicity (high LFTs!), photosensitivity
-not common
other: tolnaftate
-topical dermatophytosis (tinea)
other: ciclopirox
-penlac
-topical for nails
