Antifungals Flashcards
Amphotericin B
31-01-10
AntifungalTx: Most serious systemic mycoses (esp immediately life-threatening infxn due to rapid onset of action, broad spectrum, severe side effects)
Side Effects: Renal toxicity (most non-permanent if total cumulative dose below 3-4 g, o/w permanent, monitor hepatic and renal function), Reversible hypochromic and normocytic anemia, Flulike symptoms (fever, N/V, HA), HTN, Hypokalemia, Tachypnea
Mechanism: Polyene that inserts into membrane and binds tightly to ergosterol, decreasing membrane stability and increasing membrane permeability, inducing rapid and extensive leakage and fungi can no longer control what enters and exits membrane
Pharmacology: Broadest spectrum anti-fungal (gold standard for anti-fungal effectiveness), Difficult to administer (highly lipophilic, given as toxic detergent suspension to hold rx), Rapid onset of action (affects existing ergosterol and not synthesis), Prolonged therapy, Forms = IV, intrathecally (push into spinal fluid, tx fungal meningitis), intraperitoneally (tx localized infxn in ab cavity), NO oral or GI absorption
Flucytosine
31-01-16
Antifungal
Tx: Serious infxn (Candida, Cryptococcus, narrow spectrum), Synergistic combo with amphotericin B (never used alone, reduces dose of ampho to minimize TCD)
Side Effects: Extreme caution in those with renal insufficiency (rx accumulates, increased side effects) or bone marrow depression, Reversible hepatic enz, Leukopenia and thrombocytopenia (decreased WBC and platelets, need monitoring, potentially fatal), GI (N/V/D, enterocolitis)
Mechanism: Cytosine analog with fluorine (5-FC) that is converted by cytosine deaminase of susceptible fungi into 5-fluorouracil, which selectively inhibits fungal DNA and RNA synthesis (cells not effective at converting 5-FC into 5-FU, less side effects)
Pharmacology: Static, Excreted via urine
Fluconazole
31
Antifungal - Triazoles
Tx: Serious infxn (narrower spectrum than ampho), Cryptococcus meningitis (esp. after ampho therapy), Candida (narrowest candida coverage among triazoles, some albicans and glabrata, many sites incl. CNS and urinary since active rx in urine)
NOT C. krusei, Immediately life-threatening infxn (less rapid onset of action since synthesis affected, which only occurs during fungal growth)
Side Effects: Less than ampho, Lowest incidence among triazoles of mild hepatotoxicity (discontinue with onset of liver dysfunction), Potent inducer of CYP3A and 2C families (inhibits metabolism of several other rx), HA, Rash, GI (N/V/D)
Mechanism: Inhibits ergosterol synthesis by inhibiting 14-alpha-sterol demethylase, fungal cytochrome P450 that converts lanosterol to ergosterol (leads to membrane instability)
Pharmacology: Static, Form = oral, Penetrates CNS, Active rx excreted in urine (tx yeast infxn in bladder)
31-02
Antifungal - Superficial Mycoses
Tx: Superficial Candida infections (only partial species coverage, vaginal single oral dose, UT, oropharynx)
Side Effects: Same, but less due to lower dose and shorter therapy
Pharmacology: Form = oral (only oral rx for superficial)
Itraconazole
31
Antifungal - Triazoles
Tx: Serious infxn (narrower spectrum than ampho), Blastomyces, Histoplasma, Candida (NOT CNS or urinary, more albicans and glabrata, some krusei)
NOT immediately life-threatening infxn (less rapid onset of action)
Side Effects: Less than ampho, Mild hepatotoxicity (discontinue with onset of liver dysfunction), Potent inducer of CYP3A and 2C families (inhibits metabolism of several other rx), HA, Rash, GI (N/V/D)
Specific contraindication: Not given with other rx metabolized by CYP3A4 (potential for serious CV events including death)
Mechanism: Inhibits ergosterol synthesis by inhibiting 14-alpha-sterol demethylase, fungal cytochrome P450 that converts lanosterol to ergosterol
Pharmacology: Static, Form = oral, IV, NO CNS penetration, NO active rx in urine, Metabolized by liver
Tx: Oropharyngeal and esophageal Candida (more deep-seeded infxn)
Pharmacology: Form = oral
Tx: Fungal toenail infxn (oral 3-mo therapy)
Side Effects: Liver dysfunction (discontinue rx), Inhibits many rx metabolism, GI (N/V/D), HA, Rash, Edema
Voriconazole
31
Antifungal - Triazoles
Tx: Serious infxn (narrower spectrum than ampho), Aspergillus (superior to ampho, has greater cure rates over time, some CNS), Candida (NOT CNS or urinary, broadest coverage), Contaminated steroid
NOT immediately life-threatening infxn (less rapid onset of action)
Specific side effects: Visual disturbances, photosensitive rash
Side Effects: Less than ampho, Mild hepatotoxicity (discontinue with onset of liver dysfunction), Potent inducer of CYP3A and 2C families (inhibits metabolism of several other rx), HA, Rash, GI (N/V/D)
Mechanism: Inhibits ergosterol synthesis by inhibiting 14-alpha-sterol demethylase, fungal cytochrome P450 that converts lanosterol to ergosterol
Pharmacology: Static, Forms = oral, IV, Limited CNS penetration (some CNS Aspergillus), Metabolized by liver and IN-active metabolites excreted in urine
Caspofungin
31-02-02
Antifungal - Cell Wall
Tx: Aspergillus in pts intolerant of/refractory to other rx (NO cross resistance with imidazoles and triazoles), Candida (esophageal and systemic, broad species coverage, incl. glabrata and krusei)
Side Effects: Generally well-tolerated, Fever, Flushing, N/V, Phlebitis at injection site
Mechanism: Inhibits fungal cell wall synthesis by noncompetitively blocking synthesis of beta (1,3)-D-glucan in filamentous fungi, resulting in cell lysis
Pharmacology: Form = IV only
Miconazole
31
Antifungals - Triazole (Superificial Mycoses)
Tx: Vaginal Candida (cream/suppository)
Side Effects: Burning, Itching, Irritation
Mechanism: Same as fluconazole
Pharmacology: Form = topical
Clotrimazole
31
Tx: Candida (oropharyngeal = troche, vaginal = cream)
Side Effects: Allergic/irritation reaction for topical, Abnormal LFT’s for oral troche
Pharmacology: Form = troche (similar to lozange, hold rx in mouth, dissolve, deliver rx to site of infxn)
Nystatin
31-02-13
Tx: -azole-resistant Candida strains (topical), Also GI Candida (oral form = not absorbed, acts in GI, no systemic toxicity)
NOT ophthalmic
Side Effects: Topical well-tolerated, Oral GI distress
Mechanism: Similar to ampho
Pharmacology: Form = topical, oral
Natamycin
31-02-14
Tx: Ophthalmic fungal infxn
Side Effects:Well-tolerated (distinct characteristic), Conjunctival chemosis, Hyperemia
Mechanism: Similar to ampho
Tolnaftate
31-02-16
Antifungal
Tx: Dermatophytes
Side Effects: Few
Mechanism: Inhibits fungal ergosterol synthesis
Pharmacology: Forms = cream, spray, powder
Tinactin
Terbinafine
31
Antifungal
Tx: Nail infxn (12-wk therapy, superior to griseofulvin for nail infxn)
Side Effects: Well-tolerated, GI (diarrhea, dyspepsia, ab pain)
Mechanism: Blocks early step in ergosterol synthesis pathway by inhibiting squalene epoxidase. Ergosterol precursor squalene has no negative feedback mechanism and accumulates to toxic level = cidal effect
Pharmacology: Cidal, Forms = oral (well-absorbed), remains in skin 12 wks after therapy stopped (admin 12 wks = 24 wk therapy)
Oral prep for dermatophyte therapy reserved for severe infxn (topical no longer effective) or pts refractory to topical therapy (nail infxn deep seeded, rx not penetrating)
Lamisil
Ciclopirox
31
Antifungal
Tx: Mild to moderate fungal nail infxn (ONLY FDA approved topical rx, often toenail infxn since feet in shoes = warm and moist envt)
Side Effects: N/A
Mechanism: Possibly inhibits metal-dependent fungal enz by metal chelation to prevent infxn of new tissue as new nail grows out (one year), NO eradication
Pharmacology: Static, Forms = topical
Griseofulvin
31-02-22
Tx: Recalcitrant dermatophytic infxn of skin, hair, nails, Therapy for children (esp. for tinea capitis)
Side Effects: Well-tolerated, Increased metabolism of several rx (CYP inducer), Contraindicated in pts with porphyria and advanced liver disease, Use with caution in pts with penicillin allergies (produced in Penicillium)
Mechanism: Interferes with microtubule function/mitotic spindle/mitosis, stopping growth and preventing infxn of new tissue (NO eradication)
Pharmacology: Form = oral
