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SMS Week 2 > Antifungals and Fungal Skin Infections > Flashcards

Antifungals and Fungal Skin Infections Flashcards

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1
Q

Are fungi autrotrophic?

A

No. They are saprophyllic heterotrophs that need to feed off dead organic matter for energy

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2
Q

How are spores and conidia different? How are they similar?

A

spores are produced thorugh sexual reproduction

conidia are produeced through asexual reproduction

they are alike in that they will be survive well in the outside environment

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3
Q

Are fungi prokaryotes or eukaryotes?

A

eukaryotes

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4
Q

What are the 3 forms of fungi?

A

yeast (unicellular, spherical, reproduce by asexualyly budding blastoconidia and forming pseudohyphae)

molds (multicellular, form threaks called hyphae)

Dimorphic - can be either a mold or a yeasr

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5
Q

What do you call a mass of hyphae?

A

mycelium

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6
Q

What do you call hyphae on parasitic fungi?

A

haustoria

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7
Q

What two proteins does the cell wall of fungi contain?

A

chitin and glucan

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8
Q

What protein is unique to fungi in the plasma membrane?

A

ergosterol

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9
Q

What are the two polyenes we learned about?

A

amohptericin B and Nystatin

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10
Q

What do polyenes (amphotericin B) do?

A

they bind to ergosterol, creating holes in the membrane allowing leakage of electrolytes

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11
Q

Is amphotericin B fungicidal or fungostatic?

A

fungicidal

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12
Q

What is the spectrum of amphotericin B? What form(s) of fungi will it be effective against?

A

It has a broad spectrum and is used for invasive systemic fungal infections im immunocompromised patients - you want to kill the whole thing

It’s active against yeasts and molds

CAN be used for CNS infections

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13
Q

What is the main adverse effect of polyenes like amphotericin B and nystatin?

A

cause nephrotoxicity in majrotiy of patients

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14
Q

ALthough resistance of the polyenes is low, what is a potential route to resistance?

A

decreased ergosterol in the membrane - no binding target

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15
Q

What are the 4 azoles we learned?

A

Fluconazole

Itraconazole

Ketoconazole

Posaconazole

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16
Q

What is the mechanism of action for the azoles?

A

they bind the fungal p450 enzyme Erg11, which blocks the production of ergosterol and causes the accumulation of lanosterol, which is toxic

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17
Q

Are azoles fungicidal or static?

A

static

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18
Q

What is the spectrum for the azoles?

A

they are the most widely used agent

the actual spectrum varies by agent

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19
Q

Can azoles be used for CNS infections?

A

no - they are a substrate for efflux pumps in the brain

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20
Q

What are the toxicities that can develop from azole use?

A

drug drug-interactions (bc they target a p450)

hepatotoxicity is the big one

neurotoxicity

AVOID DURING PREGNANCY

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21
Q

How does resistance of azoles develop?

A

altered p450 Erg11

or

Ulregulation of efflux transporters

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22
Q

How does terbinafine (lamisil) work?

A

It inhibits squalene epoxidase, which leads to a toxic accumulation of squalene

this is a more severe block in the formation of ergosterol, so it’s fungicidal

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23
Q

What is the spectrum for tebinafine (lamisil)?

A

Dermatophytes

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24
Q

What are the toxicities for terbinafine?

A

topical only!!

DD interactions with CYP2D6 substrates

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25
Resistance to terbinafine is rare, but what are some hypothetically causes?
decreased uptake, mutant binding site, and substrate for efflux transporters
26
Terbinafine is the main ingredient in what drug?
Lamisil
27
How does flucytosine work?
It's a nucleic acid synthesis inhibitor It's an antimetabolite that is selectively taken up and converted to 5-fluorouracil in fingi this blocks thymidylate synthase and interferes with DNA and RNA synthesis
28
Is Flucytosine fungistatic or cidal?
static
29
WHat ist he spectrum for flucytosine?
narrow: yeast only especially candida albicans and crytococcus
30
How is flucotyosine usually given? Can is reach the CNS?
orally yes
31
What toxicity can flucytosine lead to?
bone marrow suppression
32
How can resistance develop to flucytosine?
loss of the ocnverting enzyme loss of the transporter
33
Why is flucytosine often given with amphotericin B?
It increases uptake and decreases the liklihood of developing resistnace
34
How does griseofulvin work?
It binds to microtubules and inhibits spindle formation this leads to multinucleate cells
35
What is the spectrum for griseofulvin?
dermatophytes only you have to take it orally with lipids and then it concentrates in dead keratinized skin
36
What is the main toxicity with griseofulvin?
it's teratogenic
37
How can resistance develop to Griseofulvin?
mutations in beta tubulin note: you need to take this orally for months, so for a patient who isn't adherent, resistance mutations ar emore likely to develop
38
What class of drugs is caspofungin in?
the echinocandins
39
What is the mechanism for caspofungin?
It's a cell wall inhibitor that blocks the synhtesis of Beta (1,3)-d-glucan polysacchardie
40
Is caspofungin fingicidal or static?
cidal for candida static for aspergillus
41
What is the spectrum for caspofungin?
candida systemic infections
42
How is caspofungin given? Can is cross the BBB?
IV no - too large
43
Are there any toxicities for caspofungin?
Not really - just fever and rash at IV site
44
Any resistance for caspofungin?
unknown - new drug
45
What are the three general ways fungi can cause disease in humans?
1. hypersensitivity reactions to molds or spores 2. Mycotoxicoses - poisonoing from the toxins made by the fungus 3. Mycosis - fungus grows on or in the individual
46
What are the two cutaneous fungal infections we're worried about? What's the one subcutaneous infection? 1 opportunistic?
Cutaneous: malassezia and dermatophytes subcuaneous: sporothrix Opportunistic: candida
47
WHat are the two general ways you can diagnose a fungal skin infection? What are some of the secondary ways?
Collect a sample. Dissolve the human tissue in 10% KOH and sometimes add a stain. Then visualize under microscope and you'll see the fungus You can also use a Wood's Lamp - some fungi will fluoresce under UV-A PCR culture
48
Describe Tinea versicolor (pityrosporium versicolor) What causes it?
Malassezia furfur is a yeast that is normall part of normal flora. However, when it converts to the mold form, you get disease You get hypopigmentation or hyperpigmentation of the skin from this It requires lipids to grow, so it's found predominantly in areas rich in sebaceous glands in individuals 15-24 yr-old.
49
Besides tinea versicolor, what is malassezia associated with?
seborrheic dermatitis and scaly cradle cap
50
How does one diagnose seborrheic dermatitis caused by malassezia?
Take a sample, disolve in KOH look under wood's lamp - it will look yellow green culture it - requires olive oil!
51
If you look at a skin scraping of malassezia under a microscope, what will it look like?
spaghetti and meatballs - because it's dimorphic
52
What is the treatment for seborrheic dermatitis caused by malassezia?
selenium sulfide or ketoconazole shampoo
53
WHat are some of the diseases associated with dermatophytoses?
ringworm (tinea) jock itch athlete's foot
54
What are the three fungus species that cause dermatophytoses?
trichophyton microsporum epidermophyton
55
What is the pathogenesis of dermatophytoses?
1. monomorphic molds enter through breaks in the skin 2. they secrete proteases and keratinases to break down tissue 3. cause inflammation (kerion)
56
Why do dermatophytoses only infection the superficial layers of the skin?
they grow best at 25 degree,s and can't survive at body temp
57
How can you diagnose dermatophytoses?
KOH test grow on Sabouraud's agar
58
What is the treatment for dermatophytoses?
topical griseofulvin, terbinafine, or itraconazole
59
What is the most common causative agent for tinea pedis (athlete's foot)?
trichophyton rubrum
60
WHat do trichophyton rubrum infections look like and where do they often occur?
They cause sperptein lesions with central clearing they like moist areas of the skin
61
What does it mean to say the trichophyton rubrum is anthrophilic?
it's spread by human contact can be on moist areas of skin or can be carried on clothing
62
What two microsporum species will cause dematophytoses?
microsporum canis (from cats and dogs - zoophilic) Microsporum fulvum (geophilic - from soil)
63
What areas of the body are often infected with microsporum?
hair and skin
64
How can one differentiate between a trichophyton and microsporum infection?
A microsporum infection will look blue-green under a wood's lamp
65
How can one distinghish epidermophyton infections from the other two species (trichophyton and microsporum)?
Epidemrophyton lacks microconidia - they get the macroconidia but not the smaller microconidium
66
How does one get a sporothrix schenckii infection?
it grows on plant matter and you get the infection through puncture wounds
67
Describe the pathogenesis of a sporothrix schenckii infection. What does it look like?
It causes rose gardener's disease the fungi enter skin throguh puncutre wounds and then spread from initial lesion along lymphatic channels, forming a chain of nodule lesions which can spread to bones and joints
68
How does one diagnose Rose Gardener's disease?
There will not be eough organisms for scraping and KOH So...biopsy the lymph node and culture in Sabourad agar containtin antibiotics You can also grow it at 2 temperatures to confirm dimorphism
69
What is the treatment for sporothrix schenckii?
oral itraconazole for 3-6 months
70
What are some infections associated with candida albicans?
diaper dermatitis angular cheilitis (at corners of mouth\_ toenail infections (paronychia) oropharygeal thrush vaginal yeast infections also systemic infections in immune compromised individuals
71
What does it mean to say a candida albicans infection is usually commensal/endogenous?
it means that candida is usually normal flora, but when people get infections its due to overgrowth of the fungus that was already present
72
How is candida diagnosed?
Usually just by clinical appearance, but you can do skin scraping
73
What would chronic mucocutaneous candidiasis suggest?
a T cell dysfunction or diabetes
74
WHat is the treatment for candida?
keep the skin dry and use an azole cream like clotrimazole
75

SMS Week 2 (9 decks)

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