Antimicrobial 6: Antifungals Flashcards
Name the Common Fungal Infections: (4)
- Ringworm
- Jock itch
- Athlete’s Foot
- Fungal Nail Infections
What are Fungi?
• Fungi are non-motile eukaryotic cells that are
parasitic or saprophytic in nature
• ~50 species of fungi are pathogenic in humans
• Most fungi only cause systemic infections in
immunocompromised individuals
– ‘dimorphic’ fungi can infect healthy individuals
What are 2 types of Antifungals?
• Naturally occurring antifungal antibiotics (polyenes &
echinocandins)
• Synthetic drugs (azoles & fluorinated pyrimidines)
Drugs for Fungal Infections
Slide 6 & 7
See slide 6 : Drugs for Fungal Infections
See slide 7 : fungal infections and typical 1st choice of
antifungal drug therapy
Amphotericin
Characteristcs
Amphotericin is an antifungal antibiotic that is structurally a very large macrolide (belongs to polyene group of antifungals)
Amphotericin
MOA
Oral only if fungal infection in GI tract
• Acts on the fungal cell membrane; its hydrophilic core
creates a transmembrane ion channel resulting in the loss of intracellular K + and disrupting cellular
permeability and transport systems
• Has a high affinity for ergosterol, a fungal membrane
sterol not found in mammalian cells
Amphotericin
AE
Oral only if fungal infection in GI tract
• * Hypotension • * Renal toxicity: 80% individuals renal toxicity - drug binds to prox tubule in kidneys - 25% hypokalemia and hypomagnesia • * Hypokalemia • * Thrombocytopenia
- Rigor, fever, chills and headache
- Local thrombophlebitis
Nystatin
MOA
AE
- a polyene antibiotic with similar MOA to amphotericin
- may cause nausea, vomiting, diarrhea
primarily for candida infections of skin, GI tract
Griseofulvin
Characteristics
Narrow-spectrum antifungal isolated from Penicillium
griseofulvum
Griseofulvin
MOA
Binds to fungal microtubules and interferes with mitosis
Griseofulvin
AE
- Photosensitivity
- GI upset
- Headaches
- Allergy (rashes, fever)
- Contraindicated in pregnancy
Echinocandins
Characteristics
Echinocandins are synthetic modifications to echinocandin B ( Aspergillus nidulans ) and include caspofungin, anidulafungin & micafungin
- caspofungin: fungistatic for Aspergillosis infections
- anidulafungin & micafungin: fungicidal invasive candiasis infections
Echinocandins
MOA
Inhibit 1,3-β-glucan synthase to impair 1,3-β-glucan production (polymer), which is necessary for structural integrity of the fungal cell wall
IV
Echinocandins
AE
- Hepatotoxicity (micafungin), monitor liver enzymes
- Nausea & vomiting
- Diarrhea
- Rash
Azoles
Characteristics, name 4
Azoles are synthetic broad-spectrum fungistatic agents – Ketoconazole – Fluconazole – Itraconazole – Miconazole
Azoles
MOA
- Azoles inhibit the fungal cytochrome P450 3A enzyme
(lanosine 14α-demethylase), which prevents ergosterol formation from lanosterol - Results in impaired replication, fungistatic
- if doing combo therapy, won’t work with amphotericin, no sterol to bind to
Azoles
AE
- Stevens-Johnson syndrome (fluconazole &
itraconazole)
- Stevens-Johnson syndrome (fluconazole &
- Gynecomastia (ketoconazole), cannot make steroids
- Hepatotoxicity
- GI disturbances (nausea, abdominal pain)
- Headache
- Pruritus
Flucytosine
MOA
Orally active antifungal that is converted into 5-
fluorouracil (only within fungal cells), which inhibits
thymidylate synthetase and subsequent DNA synthesis
Flucytosine
AE
- Neutropenia
- Alopecia: gut microbiota can convert flucytosine to 5-fluorouracil, contribute to alopecia
- Hepatitis
- GI disturbances
- Anemia
Terbinafine
MOA
• Lipophilic fungicidal compound that inhibits squalene
epoxidase, which is required for synthesizing
ergosterol from squalene
• Naftifine is thought to act via a similar mechanism of
action
Terbinafine
AE
usually self limiting
- Arthralgia & myalgia
- Hepatitis
- GI disturbances
- Rashes & itch
- Headache & dizziness
Summary
_____ has affinity for ergosterol and its hydrophilic core creates a transmembrane ion channel resulting in the loss of intracellular K + and disrupting cellular permeability and transport systems
Amphotericin
Summary
\_\_\_\_ inhibit 1,3-β-glucan production, which impairs structural integrity of the fungal cell wall - Drugs in this class include caspofungin, anidulafungin, and micafungin
Echinocandins
Summary
____ inhibit the fungal cytochrome P450 3A enzyme,
which prevents ergosterol formation from lanosterol
- Interferes with fungal replication
Azoles
Summary
____ is converted into 5-fluorouracil (only within
fungal cells), which inhibits thymidylate synthetase and
subsequent DNA synthesis
Flucytosine
