Term
| Which fungi are obligate animal parasites? |
|
Definition
- Candida albicans - yeast, part of normal flora
- Trichophyton rubrum - ringworm |
|
|
Term
| What fungi are types of tinea dermatophytes? |
|
Definition
- Trichophyton
- Microsporium
- Epidermphyton
**Live on the skin |
|
|
Term
| What fungi are types of yeasts? |
|
Definition
- Candida albicans
- Candida parapsilsosis - due to candida tx
- Cryptococcus neoformans - fungal meningitis |
|
|
Term
| What fungi are thermally dimorphic? |
|
Definition
- Blastomyces dermatitidus
- Paracoccidiodes brasiliensis
- Coccidioides immitus
- Histoplasma capsulatum
**Change shape at different temperatures |
|
|
Term
| What fungi are infectious molds? |
|
Definition
|
|
Term
| What are characteristics of tinea/Dermatophyte infections |
|
Definition
- Get nutrients from keratin present in hair, skin, and nails
- Named by site of infection: unuium (nails), capitis (hair) |
|
|
Term
| What are characteristics of yeasts? |
|
Definition
- Albicans most common
- Parapsilosis seen in NICU, nosocomial infections
- Vaginal and thrush infections, can be life threatening in the immunocompromised |
|
|
Term
| What is Cryptococcal meningitis? |
|
Definition
| Fungal meningitis - fatal unless treated quickly |
|
|
Term
| What are characteristics of thermally dimorphic fungi? |
|
Definition
- Blastomyces - Miss/Ohio river valley
- Paracoccidiodes - Central and South America
- Coccidioides - SW US, Valley fever
- Histoplasma - very prevalent in Miss/Ohio river valley |
|
|
Term
| What are characteristics of a Blastomyces infection? |
|
Definition
- Blastomycosis - multiple presentations including pneumonia, chronic illness mimicing TB, and ARDS (68% mortality)
- Higher fatality in AIDS
** Miss/Ohio river valley |
|
|
Term
| What are characteristics of a Paracoccidiodes infection? |
|
Definition
- Paracoccidiomycosis - largely asymptomatic, rises upon immunocompromise
**Central and South America |
|
|
Term
| What are the characteristics of a Cocciodiomycosis infection? |
|
Definition
- 1/2 asymptomatic, can cause fungal meningitis
**SW US - valley fever |
|
|
Term
| What are the characteristics of a Histoplasmosis infection? |
|
Definition
Mostly asymptomatic, can cause flu-like symptoms and travel to other organisms
**Also Ohio/Miss river valley |
|
|
Term
| What are characteristics of an Aspergillus infection? |
|
Definition
More common in AIDS or the immunocompromised
- Allergic aspergillosis
- Invasive aspergillosis generally fatal |
|
|
Term
| What are targets for antifungal therapy? |
|
Definition
NOT cell walls!
- Cholesterols called ergosterol
- Squalene epoxidase inhibits formation of lanosterol
- Demethylase prevents formation of ergosterol, lanosterol builds up |
|
|
Term
| What is the main steroid in fungal membranes? |
|
Definition
- Ergosterol - Has 2 double bonds in the B ring, and a double bond in the side chain. Ring system is flatter
- Squalene uses Epoxidase to make Lanosterol, Demethylase used to make Ergosterol. Both enzymes are drug targets |
|
|
Term
| What drug is a polyene membrane disruptor? |
|
Definition
- AmphotericinB/Fungizone
- Is amphoteric, hydrophili, and lipophilic
**Binds to ergosterol, forming pores and causing membrane leakage |
|
|
Term
| What are considerations for AmphotericinB? |
|
Definition
- POORLY selective - has many side effects:
- Liver and kidney toxicity
- Do not give with other nephrotoxic drugs such as Aminoglycosides
- Large drug = slow IV push. Formed w/ lipids to improve deliver (Colloid and lipid vesicles) |
|
|
Term
| What is the spectrum for Amphotericin B? |
|
Definition
| All fungi! Not used often due to extreme toxicity. |
|
|
Term
|
Definition
A polyene membrane disruptor like Amphotericin B, but is not absorbed GI/vaginal/Skin. HIGHLY TOXIC
**ONLY works against Candida albicans --> used topically & via suspension for thrush and yeast to avoid toxicity. NEVER IV. |
|
|
Term
|
Definition
Inhibit the demethylase enzyme - conversion of lanosterol to ergosterol. Fungi can still incorporate lanosterol into cell membranes, but dies due to a weak membrane
**Much higher affinity for fungal enzyme |
|
|
Term
| How are Azoles metabolized? |
|
Definition
| Extensively by first pass metabolism - 3A4. Drug ties up the enzyme, increasing concentrations of ANYTHING else that needs 3A4 metabolism (taken advantage of w/ cyclosporine to decr dose) |
|
|
Term
| What drugs are Azole antifungals? |
|
Definition
- Itraconazole
- Ketoconazole
- Fluconazole
- Posaconazole
- Voriconazole
- Topicals: Clotrimazole, Tioconazole, Terconazole, Butoconazole, Oxi, Mico, Keto, Eco |
|
|
Term
| How do fungi become resistant to azoles? |
|
Definition
| Mutation in ERG11, a gene in demethylase. The drug can no longer fit into the active site. Increased efflux also seen. |
|
|
Term
| What is Ketoconazole used for? |
|
Definition
- Covers all fungi except aspergillus. Used to cover Pityrosporum which causes dandruff
- Does not work in AIDS and meningitis
- AE: 3A4, N/V, menstrual effects, decr libido, TERATOGENIC |
|
|
Term
| What is the drug of choice for NONMENIGEAL dimorphic infections? |
|
Definition
Itraconazole/Sporonox
Also works on all other kinds of fungi. Better side effect profile than ketoconazole.
**Still a 3A4 substrate - will increase statins! |
|
|
Term
| What is Posaconazole/Noxafil used for? |
|
Definition
Tx of invasive Aspergillus and Candida in the immunocompromised
Still 3A4 interactions |
|
|
Term
| What drug causes Candida resistance? |
|
Definition
Fluconazole/Diflucan - 2C9 metabolism (warfarin), crosses BBB!
TX: Candida, Cryptococcal meningitis, Coccidioides induded meningitis (Valley fever)
**Does not work on other 3 dimorphic fungi or Aspergillus, Tinea |
|
|
Term
| How is Voriconazole/Vfend used? |
|
Definition
| SAME as Fluconazole, except used to treat INVASIVE Aspergillosis |
|
|
Term
| How do Squalene epoxidase inhibitors work? |
|
Definition
Inhibit Squalene epoxidase, squalene builds up into a toxic metabolite. High affinity
**Only used for tinea infections |
|
|
Term
| What drugs are Squalene epoxidase inhibitors? |
|
Definition
- Naftifine/Naftin
- Terbinifine/Lamasil - oral
- Butenafine/Mentax
- Tolnaftate/Tinactin |
|
|
Term
| What is flucytosine/Ancobon? |
|
Definition
Converted by deaminase to 5-FU --> competition for thymine. Agent gets triphosphorylated and stuck in DNA. Cell dies.
**Used w/ Amphotericin B in cases of resistance --> Candida and Cryptococcus |
|
|
Term
| How does Griseofulvin work? |
|
Definition
Incorporated into keratin to treat tinea, tinea cannot eat the keratin
**High dose suppresses cancer? |
|
|
Term
| What drugs are Echocandins? |
|
Definition
- Caspofungin/Cancidas - lysis of cell wall. ONLY Aspergillus and resistant Candida
- Anidulafungin/Eraxis
- Micafungin/Mycamine
**Inhibit beta glucan synthase |
|
|
