PHR 926 fungi map Block4

what are the 2 types of molds?

1) septate hyphae

2) Aseptate hyphae

what is an example of a septate hyphae mold?

-Aspergillus

what is an example of a Aseptate hyphae molde?

-zygomycetes (aggressive)

what are the three common types of zygomycetes?

1) mucor

2) Rhizopus

3) others

what are the important fungal structures of mold?

1) hyphae

2) conidia

what does hyphae look like?

-long filament structures that are either septate (have branches) or aseptate (no branches)

what does conidia look like?

-asexual, non-motile spores produced by fungi, particularly in the group Hyphomycetes

what is dimorphic fungi?

-has 2 shapes

-presents itself based on location

-generally endemic to certain areas

what are the 3 common dimorphic fungi?

1) coccidoides

2) Histoplasma

3) Blastomyces

what kind of dimorphic fungi will you find in kentucky?

1) Histoplasma

2) Blastomyces

what are the 2 types of yeast?

1) candida spp.

2) cryptococcus neoformans

what are the 4 common different types of candida spp?

1) C. albicans

2) C. glabrata

3) C. parapsilosis

4) C. tropicalis

what are common fungal habitats?

1) decaying organic matter

2) fecal matter

3) soil

4) skin and GI tract (mostly candida)

what are common characteristics of ALL fungi?

1) eukaryotic

2) nonmotile

3) aerobic

4) saprophytic

what antifungal drug is a DNA synthesis inhibitor?

-flucytosine

which drugs are polyenes?

1) amphotericin B

2) nystatin

what is the MOA of polyenes?

-bind to ergosterol to form pores in cell membrane

what are notable ADRs of amphotericin B (original formulation)?

-toxicities can be severe (but are improved with lipid product version)

-kidney injury (nephrotoxicity)

-infusion related reactions

true or false?

amphotericin B only comes in an IV form?

true

what are the 3 IV formulations for amphotericin B?

1) conventional amphotericin B

2) amphotericin B lipid complex

3) liposomal amphotericin B

what is the MOA of echinocandins?

-target cell wall

-inhibit glucan synthesis

-all are IV only

what are the echinocandins?

1) micafungin

2) anidulafungin

3) caspofungin

what is the MOA of AZOLs?

-are cell membrane active

-inhibit ergosterol synthesis

what drugs are AZOLs?

-anything ending in AZOL

1) fluconazole

2) itraconazole

3)voriconazole

4) Posaconazole

5) isavuconazole

describe fluconazole

-IV and oral formulations

-moderate drug interactions

-both renal and hepatic elimination (CYP3A4)

what spectrum of fungi does fluconazole cover?

1) cryptococcus

2) candida spp. (does not cover C. glabrata)

what are the possible toxicities of fluconazole?

-pretty safe drug

-occasional liver injury

describe itraconazole

-oral only

-can cause liver injury

-solution better absorbed than capsule

-a lot of DDI

what spectrum of fungi does itraconazole treat?

1) cryptococcus

2) candida spp

3) aspergillus

4) dimorphic

describe voriconazole

- IV and oral

- a LOT of DDI

-fully metabolized by liver (3 different CYP enzymes)

-IV formulations have a nonaqueous diluent which is renally eliminated

-non-linear elimination

what are the possible toxicities for voriconazole?

-liver injury

-melanoma (long-term use)

-visual disturbances (will go away once you stop voriconazole)

what is the spectrum of fungi that voriconazole covers?

1) cryptococcus

2) candida spp.

3) aspergillus (first line therapy of choice for this fungi)

4) Dimorphic

describe Posaconazole

-IV and oral formulations

-can cause liver injury

-fully metabolized

what is the spectrum of fungi that Posaconazole covers?

1) cryptococcus

2) candida spp.

3) aspergillus

4) dimorphic

5) zygomycetes

describe isavuconazole

- IV and oral formulations

- can cause liver injury

- fully metabolized

what is the spectrum of fungi that isavuconazole covers?

1) cryptococcus

2) candida spp

3) aspergillus

4) dimorphic

5) zygomycetes

- note how same spectrum of coverage as Posaconazole

what are 3 things that we are actively doing that is increasing fungi infections?

1) transplants

2) antimicrobial treatment

3) other immune suppressing drugs

what similarity between humans and fungi causes delay in new treatment options and some toxicity with antifungals?

-ergosterol (in fungi) is structurally similar to cholesterol (in humans)

true or false?

fungi are not here (generally) to infect humans

true

true or false?

when we take away immune defense, fungi can cause disease

true

where are cocidoides generally found?

in desert and south west

what is the most common (and possibly most relevant) candida yeast?

-C. albicans (susceptible to drug treatment)

what is the most worrisome and resistant candida yeast to treat?

C. glabrata

which two types of candida yeast are uncommon?

1) c. parpsilosis

2) C. tropitcalis

true or false?

cryptococcus neoforms can occur in uncontrolled HIV and some cancer patients. the ability to control and prevent HIV has decreased the rate of this yeast

true

true or false?

dimorphic is NOT a true mold

true

true or false?

Polyenes look for already synthesized ergosterol and clump them together in a circle with a hole in the middle which them forms pores in cell membrane

true

true or false?

a second line drug for aspergilus is caspofungin

true

true or false

because we are not too great at treating fungal infections you will see some places start with 2 drugs at the start at treatment

true

what drugs can treat cryptococcus?

1) fluconazole

2) itraconazole

3) voriconazole

4) posaconazole

5) isavuconazole

6) amphotericin

what drugs can treat candida albicans?

1) fluconazole

2) itraconazole

3) voriconazole

4) posaconazole

5) isavuconazole

6) amphotericin

7) caspofungin

8) micafungin

9) anidulafungin

what drugs can treat candida parapsilosis?

1) fluconazole

2) itraconazole

3) voriconazole

4) posaconazole

5) isavuconazole

6) amphotericin

7) caspofungin

8) micafungin

9) anidulafungin

what drugs can treat candida glabrata?

1) voriconazole (some resistance)

2) pasoconazole (some resistance)

3)isavuconazole

4) amphotericin

5)caspofungin

6) micafungin

7) anidulafungin

what drugs can treat C. tropicalis?

1) fluconazole

2) itraconazole

3) voriconazole

4) posaconazole

5) isavuconazole

6) amphotericin

7) caspofungin

8) micafungin

9) anidulafungin

what medications can treat aspergillus?

1) itraconazole

2) voriconazole

3) posaconazole

4) isavuconazole

5) amphotericin

6) caspofungin

7) micafungin

8) anidulafungin

what drugs can treat zygomycetes?

1) posaconazole

2) isavuconazole

3) amphotericin