Table of contents
- 1. Antifungals
- 1.1. Amphotericin B
- 1.2. Azoles
- 1.3. Echinocandins
- 1.4. Flucytosine
- 1.5.
- 1.6. Nystatin
- 2. Antivirals
.
Antifungals
Amphotericin B
- Long cycle polyene binds ergosterol in membrane, leaks K+ --> rapid fungal death.
- FUNGICIDAL
- Two forms:
- Deoxycholate form (ABD) (STANDARD)
- Lipid preparations (less toxic, same efficacy, but very high $$$)
- Use if renal dysfunction (see below)
- Toxicity:
- Nephrotoxic
- vasoconstriction of renal arterioles, decrease in GFR.
- Impairs proximal and distal tubular reabsorption --> K+, Mg, HCO3 wasting.
- Often reversible, except if long-term then:
- Permanent nephron loss and damaged tubular basement membrane.
- Hydrate before therapy to decrease risk.
- Fever
- Not allergic, no anaphylaxis.
- Can pre-medicate with acetaminophen or 25-50mg of hydrocortisone.
- Phlebitis
- High incidence of phlebitis
- Use central venous line.
- Nephrotoxic
- Clearance:
- Not affected by hepatic/renal dysfunction.
- Degrated slowly, accummulates in machophages. (Detect in serum 7w post-tx)
- Poor CSF penetration.
- Coverage:
- Most effective for systemic fungal infections
- Resistance:
- Alters sterol structure - can only grow on mucusal surfaces or urine.
- Candida lusitaniae (initially susceptible but then resistant)
- Fusarium
- Pseudalles-cheriba boydii
- Alters sterol structure - can only grow on mucusal surfaces or urine.
Azoles
Azoles | |
---|---|
Drugs | Two classes:
|
Mechanism: | Inhibit Cytochrome P450-dependent demethylation system
|
Absorption | Good PO, often better with food |
Clearance | Hepatic |
Coverage | Broad DO NOT cover:
|
Resistance
| |
| |
Clinical Use |
|
Toxicity |
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Echinocandins
Echinocandins | |
---|---|
Drugs | Derived from echninocandin B
|
Mechanism: | Block cell wall polysaccharide |
Absorption | Good PO, often better with food |
Clearance | Hepatic |
Coverage | Aspergillus, Candida (even if resistant)
NOT active: Cryptococcus |
Resistance
| |
| |
Clinical Use |
|
Toxicity |
|
Interactions | Cyclosporin, Tacrolimus, Dilantin, Tegretol, etc.. |
Flucytosine
Flucytosine | |
---|---|
Drugs | Flucytosine |
Mechanism: | Deamination + phosphorylation --> 5-FU --> inhibits thymidylate synthetase (impairs DNA/RNA synthesis) |
Absorption | Good PO |
Clearance | |
Coverage | Aspergillus, Candida (even if resistant)
NOT active: Cryptococcus |
12% of C. albicans and 3-5% of Cryptococcus neoformans demonstrate resistance. | |
Clinical Use |
|
Toxicity |
|
Interactions | |
Notes: |
Nystatin
- Only Effective for Candida
- Do not use on tinea or other dermatophyte infections
Antivirals
Acyclovir/Valacyclovir/Famciclovir
Block DNA Transcription | |
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Drugs |
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Mechanism: |
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Absorption |
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Clearance |
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Coverage/ Clinical Use |
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Toxicity |
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Ganciclovir & Valganciclovir
Block DNA Transcription | ||
---|---|---|
Drugs |
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Mechanism: |
| |
Absorption |
| Good CSF Penetration |
Clearance |
| |
Coverage/ Clinical Use |
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Toxicity |
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