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118 Cards in this Set

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Key differences between Animals and Fungi?
-Ergosterol in membrane instead of Cholesterol
-have a Cell Wall made of chitin, glucan, and mannan
Type of nutritional organism Fungi are?
Heterotrophs = cannot synthesize their own nutrients, but assimilate nutrients from surroundings
How is being a heterotroph imporant in the way Fungi cause disease in humans?
Fungi secrete enzymes that digest the substrate..aka our tissue (amylase, lipase, cellulase, proteinase)
2 morphological forms of fungi?
Yeasts

Filaments
Filaments are long, hollow structures filled with __1__ and often divided by __2__
1. cytoplasm
2. cross-walls
Filaments are larger than __1__, they can break apart and each fragment can __2__. The filament form allows for __3__
1. macrophages
2. start a new colony
3. tissue penetration
Yeasts are __1__-cellular and divide by __2__
1. uni
2. fission (budding)
Host defense against filaments:

Host defense against yeast:
Oxidative burst


Phagocytosis
Pathogenic Fungi:
-some have the ability to grow at __1__ degrees.
-Some have a __2__ which protects them from immune system
-__3__ allows them deep penetration of the lung where systemic infection can start
1. 37' C
2. polysaccharide capsule
3. small spore size
Interaction with _______ may predispose fungi to be parasites of higher animals
soil amoebae
4 major groups of fungi
Ascomycetes
Basidiomycetes
Zygomycetes
Imperfect fungi
The four groups are differentiated based on _________
their spore types
List some examples of Asexual spores
Arthrospore
Chlamydospore
Fusarium conidia
Alternaria conidia
Neurospora conidia
Asexual spores have these characteristics
-vary in size from a few microns to hundreds of microns
-often very Hydrophobic
-some have mucilage
What stage of fungal life cycle is most relevant to allergy sufferers?
Spores are often allergenic
-dead spores maintain allergenicity
Most numerous spores in the air we breath?
Conidia, but also smut spores and ascospores
Type of Hypersensitivity caused by spores?
Type I: spore binds to IgE on Mast cells
4 most common environmental fungi
Aspergillus
Alternaria
Cladosporium
Penicillium

*their spores are common indoors and outdoors*
Spores are common after _______ events

Spores are not common in these environments: _____
rain

desert/arid
Some ______ infections can be related to fungal presence
sinus

*Eosinophilic Fungal Rhinosinusitis
*difficult to tell if fungi are growing in sinus or incidental
Where are typical locations of fungi indoors?
Moisture places
-shower
-water ducts
-furnace filters
-house plants
Household item that can kill fungi
bleach
Most common fungal toxins and most significant public health risk associated with fungi
Mycotoxins in grain
-Estimated # of different mycotoxins: __1__
-Toxin also common in __2__
-__3__ poisoning is much less common than mycotoxin exposure
1. 300-400
2. nuts
3. mushroom
Aflatoxin is from grains and nuts infected by ________
Aspergillus
Explain how Aflatoxin is activated
It is metabolized to its active form in the Liver
What can complicate Aflatoxin ingestion?
HBV + Aflatoxin exposure have higher incidences of LIVER CANCER
Alkaloid mycotoxins include these 3
1. Clavicepes infected rye -> Lysergic Acid (LSD)
2. St. Anthony's fire = hallucinations, cramps
3. Neurotoxins in infected grains
Fumonisin mycotoxins come from __1__ infected __2__
-It is associated with __3__ CA.
-causes disease in __4__
1. Fusarium
2. Wheat
3. Esophageal
4. farm animals
Example of a Fumonisin mycotoxin
Vomitoxin

*produced by Fusarium
Fungus that causes "sick building syndrome"
Stachybotrys Chartrum
Stachybotrys Chartum mycotoxins

Concentration of infected material that can contain a lethal dose
Trichothecenes
Satratoxin F, G, and H

100-1000 cm'2
People in contaminated buildings have elevated titers of antibodies to:
-S. Chartum: __1__
-Satratoxin: __2__
1. IgA, IgM, IgE

2. IgG

*Stachybotrys is relatively uncommon compared to enviromental Alternarium, Cladosporium, Aspergillus
Gliotoxin is produced by these 2 fungi
Aspergillus
Gliocladium
3 properties of Gliotoxin

Gliotoxin mechanism?
1. highly toxic
2. immunomodulatory
3. stimulates apoptosis

Mechanism: inhibits nuclear factor kappa B
Are most cases of Mushroom poisoning lethal or non-lethal?
Non-lethal
What is the most common symptom of Mushroom poisoning?
Vomiting
Amanita toxins are __1__ polypeptides which inhibit __2__
1. cyclic
2. RNA Polymerase
Amanita toxins can lead to death within __1__ days without a __2__ transplant
1. 6
2. liver
Ibotenic Acid toxin is produced by __1__ and causes these symptoms: __2__
1. Amanita muscaria
2. nausea, vomiting, confusion, visual distortion
Psilocybin causes these clinical effects
Hallucinations or Perceptual distortions
Why are Anti-fungal therepies limited?
Fungi are closer to animals than bacteria are
-many drugs that kill fungi are bad for people as well
Most anti-fungal therapies depend on the presence of ________ in the fungal membrane
Ergosterol
Fungi use __1__ in their membranes

Animals use __2__ in their membranes
1. Ergosterol

2. Cholesterol
List the pathway to Ergosterol synthesis
Squalene --> Lanosterol --> Ergosterol
2 antifungal classes that target Squalene Epoxidase
Thiocarbamates
Allylamines
Thiocarbamates and Allylamines are effective against __1__ but less so against __2__
1. Dermatophytes
2. yeast
Squalene accumulation can be ______ to the fungi
toxic
List 4 Allylamines
Terbinafine
Naftifine
Amorolfine
Butenafine

*all end in FINE
Lamisil is also known as _________

What is it effective against?
Terbinafine

Oral or Topical
-effective against molds, dermatophytes, some candida yeasts
What is the 1st commited step in Ergosterol synthesis?
Squalene
Terbinafine is marketed to __1__ because of higher frequency of __2__ infections
1. Athletes
2. toenail/foot
Terbinafine (lamisil):
-__1__ due to squalene accumulation.
-1/2 life is __2__ following oral administration
-take orally for __3__
-topical OTC for __4__ or _5_
1. FUNGICIDAL
2. 4.6 hours
3. Onychomycosis (nail infection)
4. ringworm or athletes foot
Oral Terbinafine has reduced clearance in patients with __1__ or __2__ impairment
1. liver
2. kidney
Terbinafine has a ______ times higher affinity for fungal squalene epoxidase than for human
4000
Azoles bind to _____ and inhibit __________
P450 (14DM)

Lanosterol Demethylase
(14 alpha-demethylation of lanosterol)

*newer Azoles have a higher specificity for fungal enzyme while older azoles cross react with human P450's
Fluconazole trade name
Diflucan
__________ biochemistry is markedly effected by reduction in renal fxn
Fluconazole
Fluconazole (Diflucan):
-half life: __1__
-effective against __2__
1. 30 days
2. yeasts, widely used for serious fungal infections
Fluconazole: fungistatic or fungicidal?
Fungistatic

*need immune system to clear organisms
Type of Fluconazole formulations available?
Oral or IV
Antifungal drug that penetrates into all body fluids
Fluconazole
Fluconazole is marketed for _________ infections
Vulvovaginal candidiasis
Fluconazole:
-__1__% is excreted in urine unchanged
-prophylactic in __2__
1. 80%
2. HIV and transplant recipients
Itraconazole formulations available
Oral or IV
_______ Itraconazole is unpredictable
Oral
-best with food
Itraconazole inhibits a broad range of fungi except __1__ and __2__
Fusarium

Zygomycetes
Itraconazole trade name
Sporanox
Property of Itraconazole
Lipophilic = accumulates in nails and fatty tissue
Solution or IV Itraconazole are used for some systemic infections especially in _________
IC'ed patients
Antifungal that is contraindicated in patients with Heart or Liver Disease
Itraconazole
40% of Itraconazole is excreted as _________ in urine
inactive metabolites
Issue with Itraconazole
serious drug interactions
Voriconazole trade name:

It is marketed for:
Vfend

Aspergillosis
Voriconazole is fungistatic to these fungi
Candida
Aspergillus
Cryptococcus
Blastomyces
Coccidioides
Histoplasma
Fusarium
Penicillium
Voriconazole is not effective against ________
Zygomycetes
Voriconazole half-life is ________
Dose dependent, enzyme saturation
Survival rate of 71% in patients with solid organ tranplants on __1__, compared to 58% with __2__
1. Voriconazole
2. Amphotericin B
Rifampicin is contraindicated with this antifungal drug
Voriconazole
Side effects of Voriconazole (2)
Visual disturbances
Hepatic issues
____% of Voriconazole is excreted as metabolites in the urine
80%
-<2% is unchanged
This new azole drug is broadly active but cross resistance with Itraconazole or Fluconazole.
It has a stronger inhibition of P450 target than Itraconazole
Posaconazole (Noxafil)
Posaconazole trade name
Noxafil
New azole drug with similar activity to Fluconazole and Voriconazole and Itraconazole
Ravuconazole
Class of Antifungals that disrupt fungal membrane by forming pores
Polyene antibiotics (macrolides)
Are polyene antibiotics fungistatic or fungicidal?
Fungicidal
2 polyene antibiotics
1. Amphotericin B

2. Nystatin
Nystatin was developed from ______.

There are new _____ formulations
soil Actinomycete

Liposomal
Topical Nystatin is used for: 1

Nystatin lozenges are used for: 2

Oral Nystatin for: 3
1. Cutaneous candidiasis

2. Oropharyngeal candidiasis (thrush)

3. vulvovaginal candidiasis
Is nystatin resistance common or uncommon?

What is Nystatin not useful for?
uncommon

Systemic infections
Nystatin is not presently useful for ________ treatment
systemic
Amphotericin B: fungicidal or fungistatic?
Fungicidal
Amphotericin B has broad range activity except against __1__ and __2__
1. Fusarium

2. Malassezia
Amphotericin B resistance is uncommon but can be clinically relevant in _______
Candida
Amphotericin B plasma half-life: _1_

Elimination half-life: _2_
1. 24 hours

2. 15 days
What is the first line of defense for Systemic and Opportunistic infections?
Amphotericin B
Serious side effects of Amphotericin include _______
nephrotoxicity
-lipid and liposomal formulations help with this
Most treatments with Amphotericin B require _____ administration
IV

*oral absorption is very low
Cerebral infections may require _______ administration of Amphotericin B
intrathecal
Amphotericin B is sometimes administered in combo with _______
Flucytosine for Cryptococcal meningitis
Dosing of Amphotericin B is based on _______
cumulative dose
-.3 to 1.5 mg/kg over 1-4 hrs
Amphotericin B accumulates in these 3 parts of the body
Spleen
Liver
Lung
Lipid formulation of Amphotericin B = 1

Liposomal formulation = 2
1. Abelcet

2. Ambisome
-for pediatric administration
Griseofulvin is indicated for: __1__
-half life = _2_
-cheap and is used for: _3_
-side effects: _4_
-currently clinical trials are looks at efficacy vs. __5__
1. Dermatophytes
2. 9-24 hrs
3. tinea capitis
4. Headache, rash, confusion
5. Terbinafine
Griseofulvin is isolated from ________
Penicillium
Griseofulvin disrupts _______
mitotic spindle = inhibits mitosis
Griseofulvin side effects
HEADACHE
rash
confusion
photosensitivity
fatigue
nausea
peripheral neuropathy
Echinocandins are inhibitors of ____________
cell wall synthesis
List 3 Echinocandins
Caspofungin
Anidulafungin
Micafungin

*all end in FUNGIN
Echinocandins block synthesis of _________

Derivatives of the natural product ________
Produced by _______
1-3-beta glucan

pneumocandin Bo
Glarea Iozoyensis
Trade name of Caspofungin
Cancidas
What is Caspofungin?
An Echinocandin = inhibit glucan synthesis
Caspofungin properties
-poor oral bioavailability
-slow elimination (6-8 days)
Caspofungin is prescribed for these 2 things
Aspergillosis
Candidemia

*Glucan synthetase inhibitor
Most serious toxin exposure is from contaminated _____
grain
Most common symptom of mushroom poisoning is ______
vomiting
Most therapies depend on targeting ________
Ergosterol containing membranes or inhibiting sterol synthesis
Organism in which Arthrospores are the infectious molecule
Coccidiomycosis