Antifungals

Question 1

Name the three pathogenic fungi mentioned in the lecture.

Prompt: antibiotic chrysanthemum, fumigate Vincen’ts house, thrush

Answer 1

Penicillium chrysogenum
Aspergillus fumagatum
Candida albicans

Question 2

What’s the THM about the threat of fungal infection?

Answer 2

Generally it represents ore of a nuisance than a threat, BUT if they gain systemic access and propagate it can be fatal. With antibiotics and HIV, opportunistic infections like this are rising.

Question 3

X affects skin nails and hair, Y affects superfical mucous membranes (when not systemic aka ‘diseminated’)

Answer 3

Dermatomycosis; candidiasis

Question 4

A and B are natural, whereas C and D are synthetic

Answer 4

Echinocandins and polyenes; fluoronated pyrimidines and azoles (you aren’t born an asshole, you’re made one).

Question 5

Four pathogenic fungi
It’s hard to encapsulate a mnenomic for this.
Keanu Reeves is a men’s rights activist.
Fumigate Vincent’s house.

Answer 5

Cryptococcus neoformans, aspergillus fumagatum, candida albicans, histoplasma capsulatum.

Question 6

Four pathogenic fungi (no prompts)

Answer 6

Cryptococcus neoformans, aspergillus fumagatum, candida albicans, histoplasma capsulatum.

Question 7

Which fungi in this lecture is a yeast?

Answer 7

Cryptococcus neoformans

Question 8

Which fungi in this lecture is yeast-like with myecilium-like structures

Answer 8

Candida albicans

Question 9

Which fungi is dimorphic?

Answer 9

Histoplasma capsulatum

Question 10

Which fungi is dimorphic?

Answer 10

Histoplasma capsulatum

Question 11

What are risk factors for [superficial] candidosis? (no prompts)

Answer 11

Diabetes, immunosupressants, corticosteroids, antibiotics

Question 12

What are risk factors for [superficial] candidosis? (no prompts)

Answer 12

Diabetes, immunosupressants, corticosteroids, antibiotics

Question 13

What are three filamentous fungi other than Aspergillus fumagatum?
Small spores are likely to land on your skin. Frustrates me so much I wanna get my fight on and I don’t wanna fall in any holes in case there’s fungi down there.

Answer 13

trychophyton (jock itch - tinea of the jock)
epidermaphyton,
microsporum

Question 14

What are three filamentous fungi other than Aspergillus fumagatum?
(No prompts)

Answer 14

trychophyton (jock itch - tinea of the jock)
epidermaphyton
microsporum

Question 15

Name for types of tinea - jock, foot, body, scalp.

Recall it can accrue in ya jock.

Answer 15

Cruris, pedis, capitis, corporis

Question 16

Tinea isn’t a type of fungi. It’s…

Answer 16

… the word for any time of skin infection.

Question 17

What is the precursor to ergosterol?

Answer 17

Lanosterol.

Question 18

Ergesterol depletion stops fungi from replicating. What’s a bonus effect?

Answer 18

Stops candidal hyphae from growing.

Question 19

What pharmacologically relevant effect foes ergosterol depletion have?

Answer 19

Reduces amphotericin binding.

Question 20

What enzyme do azoles inhibit?

Answer 20

Cytochrome P450 3A aka 14α-demethylase.

Question 21

Are azoles fungistatic or fungicidal?

Answer 21

Fungistatic.

Question 22

What two primary drugs are used for systemic infections?

Answer 22

Azoles and amphotericin.

Amphotericin is the gold standard but requires close medical supervision.

Question 23

Amphotericin components are structurally Gs, which are categorically a type of J.

Answer 23

polyenes; macrolide

Question 24

What’s the significance of ergosterol to amphotericin therapy?

Answer 24

Amphotericin binds with great avidity to ergosterol molecules in fungal cell membranes.

Question 25

What should you combine with amphotericin therapy - flucytosine or azoles?

Answer 25

FLUCYTOSINE - famously good synergistic effect. Absolutely do NOT combine it with azoles.

Question 26

Why is amphotericin often delivered in liposomes?

Answer 26

Because otherwise it's so pharmacokinetically stubborn. The liposome formulation also reduces side effects.

Question 27

What are the five main headings for amphotericin unwanted effects?

Answer 27

``` Nephrotoxicity Hypokalaemia Bone marrow suppression Neurotoxicity Amphoterrible effects ```

Question 28

What is the name of the two other polyenes? | I hate nyan cat.

Answer 28

Nyastatin and griseofulvin

Question 29

Cons of nyastatin as opposed to amphotericin?

Answer 29

Not absorbed through skin or mucous membranes. Limited to mycoses of the skin, mucous membranes or GI tract. Only kills candida (but is quite good at it).

Question 30

Think mitotic interference through microtubule binding, think...

Answer 30

Griseofulvin

Question 31

When do we use griseofulvin?

Answer 31

When local treatment doesn't work. BUT has to be very prolonged.

Question 32

What is 1,3-β-glucan and what fucks up it synthesis?

Answer 32

It's a fungal cell wall polymeric component whose synthesis is fucked up by echinocandins.

Question 33

How is flucytosine selective for fungi?

Answer 33

Only in fungal cells can it be converted into the antimetabolite 5-fluorouracil. Therefore it can disrupt DNA synthesis in fungal cells, but not human ones.

Question 34

What are the gentlest drugs/drug in this lecture in terms of side effects?

Answer 34

Flucytosine. Makes it easier to combine with for sure.

Question 35

Which antifungal has problems with resistance development?

Answer 35

Flucytosine.

Question 36

What are the big three side effects of ketoconazole? (biggest first)

Answer 36

Hepatotoxicity Gynaecomastia Interactions with metabolising enzymes

Question 37

Name the three specific azoles in this lecture

Answer 37

Ketoconazole Fluconazole Itraconazole

Question 38

What is basically the opposite of amphotericin when it comes to pharmacokinetics?

Answer 38

FLUCONAZOLE Well absorbed orally Even fungicidal concentrations reached in CNS, superficial mucous membranes, even skin and nails.

Question 39

Are fluconazole side effects mild?

Answer 39

Yes. Drug interactions tho. | Bonus: nausea, vomiting, rash

Question 40

Caspofungin is a ...

Answer 40

echinocandin

Question 41

``` Think... combination with amphotericin really poor absorption very gentle side effects problems with resistance, think... ```

Answer 41

flucytosine

Question 42

nystatin's sort of similar to saquinavir (viral protease inhibitor) in its side effects. What are they?

Answer 42

Nausea, vomiting, diarrhoea.

Question 43

3 griseoflulvin side effects. It's like the sun is travelling through my eyes burning my skull and sliding down into my GI tract and I need Gris the real person to use his massive body to block it out.

Answer 43

GI, photophobia, headache

Question 44

What are the two drugs in this lecture with potential liver toxicity?

Answer 44

Ketonazole, itraconozole.