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29 Cards in this Set
- Front
- Back
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Topical Antifungal Agents
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Many available, esp. OTC
Choice depends on fungus and location (creams/solutions better suited for fissured/wet places and powders are good prophylactic agents) |
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Vaginal Antifungal Agents
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Most appeciated: least messy and shortest application time.
1 150mg fluconazole (for yeast infections) |
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Treating Oral Candidiasis (Thrush)
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Clotrimazole > Nystatin
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Griseofulvin
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Historial Use
Active against dermatophytes but NOT AGAINST CANDIDA |
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Oral, SYSTEMIC therapy for cutaneous infections
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Griseofulvin (historical interest) - DONT USE IT
Terbinafin (Lamisil) |
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Mechanisms of Antifungal Medication
(general) |
Most work at plasma membrane (ergosterol synthesis, similar to our own cholesterol synthesis so issues w/toxicity)
Newer generations target beta-glucan (penicillins for fungi) |
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Terbinafin
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Nail and dermatophyte infections
Broad spectrum, oral systemic therapy Lipophilic - binds to stratum corneum and stays for a long time Enables you to bolus drug (on 1 week, off 3 weeks for 3/4 cycles) |
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Amphotericin B
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"Amphoterrible"
AMPHI - has acid/base PolyENE (multiple double bonds) - light sensitive and yellow color |
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Amphotericin B
(preparation) |
Lipophilic, mix w/biosalt (deoxycholate) and forms micelles
If mix w/salt suspension, clumps Therefore mix in D5W (dextrose/water - NO salt) ONLY |
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Amphotericin B
(mechanism of action) |
Inserts into PM
Binds to ergosterol Like staves on a barrel, forms a PORE Problem, also binds to cholesterol (will see lysis of RBCs, etc) |
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Amphotericin B
(pharmacology in body) |
In blood stream, disassociates from deoxycholate and binds LDL - plasma protein(contains tons of cholesterol)
Binds to densely vascular tissue (liver, spleen, kidneys, lungs) - which then serves as a resevoir as plasma levels fall (why amphotericin has such a long 1/2 life - 2 weeks!) |
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Why is Amphotericin especially nephrotoxic?
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Renal tubular cells have receptors for LDL (which binds amphotericin B)
When treating, avoid drugs that cause dehydration, etc You need to especially monitor their salt levels - they'll drop(K, Mg, HCO3) |
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Amphotericin B
(side effects) |
Acute: "shake and bake" (due to PGE2, TNF, IL-1 - treat with NSAID? NO! AmphiB knocks out efferent and NSAIDS knock out afferent - lose renal function!)
Chronic: normochromic/normocytic anemia |
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Lipid-associated Amphotericin B Preparations
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Fat-containing amphotericin B more efficiently target areas of infection
When they disassociat, they're picked up by HDL (vs. LDL) and therefore, have significantly less impact on Kidneys One's available: liposomal Amphitericin B (AmBisome); Amphotericin B lipid comoplex (ABLC) |
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Azoles
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Inhibit ergosterol synthesis
Fungistatic Types: imidazoles; triazoles |
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Imidazoles vs. Triazoles
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Both Azoles (block ergosterol synthesis and fungistatic)
However, triazoles have greater affinity to funal CYP450 enzymes |
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Ketoconazole
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of Imidazole class
Oral dose, requires gastric acid Toxicity limits its utility (hepatic problems) Little utility but great for treatment of patients with prostate cancer |
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Fluconazole
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Triazole
Good bioavailability Excreted in urine (good for UTIs) CSF entry Minimal toxicity |
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Itraconazole
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Triazole
Unpredictable pharmacokinetics, requires gastric acid (instituted IV alternative, but rarely used) but broad spectrum of activity |
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Azole Pharmacology
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All insoluble in water, therefore if IV, must use Beta-cyclodextrin vehicle, but accumulates in patients with renal insufficiency and possibly carcinogenic!
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Voriconazole
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Daughter of fluconazole with greater specificity (can get into CNS)
PO and IV preparation Issue: metabolized by several cytochrome enzymes (drug interactions common); abnormal electroretinograms (LSD-like trip) |
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Which azoles require gastric acid?
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Ketoconazole and Itraconazole
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Azole to treat fungal UTI?
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Fluconazole
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Azole to treat fungal CNS infection?
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Fluconazole > voriconazole > itraconazole
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Contraindication to Azole administration?
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These guys are heavily metabolized by liver, therefore numerous drug interactions
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Posaconazole
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"Daughter of itraconazole"
Adv? Advantage against zygomyces |
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5-fluorocytosine
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Interferes with DNA synthesis
Good levels at CNS/urine Toxicity? Bacteria can metabolize to 5-FU (chemotherapeutic agent) which can reach toxic levels if poor clearance mechanisms |
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What is the clinical advantage of 5-FC?
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Used w/AmB to treat cryptococcal meningitis
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Echinocandins
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Large, complicated structures
Fungicidal, act on cell wall No drug interactions (hydroxylated vs. going through CYP450 system) |
