Antifungals Flashcards
1
Q
caspofungin
A
Echinocandin- Targets Cell Wall
- MOA: inhibits glucan synthesis (weakens cell wall causing osmotic shock/lysis)
- glucan is similar to peptidoglycan and gives rigidity to fungal cell wall
- primarily active against/used for invasive Aspergillus/mold infxns, azole-resistant Candida
- given IV
2
Q
flucytosine
A
DNA Synthesis Antimetabolite- Targets Cell Replication/Division– fungistatic
- MOA: taken up by fungal cells and converted to 5-fluorouracil which competetively inhibits thymidylate synthase; 5-FUTP incorporated into defective RNA and inhibits protein synthesis
- selectively toxic to fungi b/c humans lack cytosine deaminase
- resistance common due to mutations in cytosine permease or cytosine deaminase but used in combo with Ampho B
- can cause bone marrow depression
3
Q
griseofulvin
A
Mitotic Spindle Poison- Targets Cell Replication/Division
- MOA: interacts with polymerized microtubules to block fungal mitosis
- Only used orally for systemic tx of dermatophytosis (limited use)
- induces CYPs
4
Q
amphotericin B
A
polyene
- bind ergosterol to compromise fungal cell wall
- BROADEST spectrum
- drug of choice for treating lif
- threatening systemic fungal infections, including candida, aspergillus, cryptococcus
- usually fungicidal, but may be fungistatic depending on pH, concentration, and fungal type
- selective toxicity: binds to cholesterol to a far lesser extent that ergosterol
- resistance: decrease ergosterol concentration or alternative sterols are substituted in membrane
- poorly absorbed from GI (only given PO for GI lumen infections)
- NOT absorbed from skin or mucous membranes therefore can be used topically for superficial Candida infections
- used parentally for systemic infections
- not soluble in aqueous media; reconstituted in deoxycholate
- slow IV infusion over 2-6 hours
- newer liposome formulations
- extensively metabolized and excreted by the kidney
- adverse effects: GI irritation, topical- local irritation, IV– infusion reactions (fever, chills, muscle spasm, vomiting, headache, hypotension) allergic reaction/anaphylaxis, NEPHROTOXICITY, anemia
- drug interactions: digitalis– hypokalemia and dig toxicity, azoles– induce development of resistant fungi, other nephtrotoxic drugs (cyclosporine, aminoglycosides)
5
Q
nystatin
A
polyene
- bind ergosterol to compromise fungal cell wall
- narrow spectrum, too toxic to be given parenterally
- not appreciably metabolized
- NOT well absorbed from skin, mucous, or GI tract
- uses: topical candidal infections of mucosa, skin, GI tract and vagina, drug of choice for oral moniliasis, thrush, denture stomatitis
- adverse effects: bitter/unpleasant taste
6
Q
clotrimazole
A
imidazole (2 N atoms)
- inhibit ergosterold synthesis by blocking CYP enzymes
- impair fungal cell membrane synthesis
- much less specific for fungal CYPs (more drug interactions & side effects)
- restricted to oral.topical administration for local distribution
- drug of choice for oropharyngeal candidiasis in AIDs
7
Q
ketoconazole
A
imidazole (2 N atoms)
- inhibit ergosterold synthesis by blocking CYP enzymes
- impair fungal cell membrane synthesis
- much less specific for fungal CYPs (more drug interactions & side effects)
- H2 antagonist (famotidine) interfere with absorption
- inhibit adreanl & gondal steroid hormone biosynthesis
- may cause symptomatic hepatitis that can be fatal
- use is limited because it has greatest propensity to inhibit mammalian CYPs
8
Q
miconazole
A
imidazole (2 N atoms)
- inhibit ergosterold synthesis by blocking CYP enzymes
- impair fungal cell membrane synthesis
- much less specific for fungal CYPs (more drug interactions & side effects)
- systemic use limited by toxicity
- effective topically against cutaneous candidasis
uses: oropharyngeal candidiasis & vaginal candidiasis
9
Q
fluconazole
A
triazole (3 N atoms)
- MOST WIDELY USED AZOLE
- inhibit ergosterol synthesis by blocking fungal CYPs
- impair fungal cell membrane synthesis
- CNS penetration
- used to treat cryptococcal meningitis
- resistance: NOT active against molds
- good oral bioavailability and IV
- uses: systemic antifungal, oropharyngeal carndidiasis
10
Q
itraconazole
A
triazole (3 N atoms)
- inhibit ergosterol synthesis by blocking fungal CYPs
- impair fungal cell membrane synthesis
- H2 antagonsit interfere with absorption
- broader spectrum
- well absorbed in the GI tract
- uses: Aspergillus & fluconazole-resistant Candida
11
Q
terbinafine
A
allylamine
- inhibits ergosterol synthesis by blocking activity of squalene epoxidase
- primarily effective against dermatophytes
- topical or oral
- accumulates in skin, nails, fatty tissue
- co-administration with cimetidine decreases clearance by 1/3
- use: mainstay for SKIN/NAIL infections
