Antifungals Flashcards
Name the three pathogenic fungi mentioned in the lecture.
Prompt: antibiotic chrysanthemum, fumigate Vincen’ts house, thrush
Penicillium chrysogenum
Aspergillus fumagatum
Candida albicans
What’s the THM about the threat of fungal infection?
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.
X affects skin nails and hair, Y affects superfical mucous membranes (when not systemic aka ‘diseminated’)
Dermatomycosis; candidiasis
A and B are natural, whereas C and D are synthetic
Echinocandins and polyenes; fluoronated pyrimidines and azoles (you aren’t born an asshole, you’re made one).
Four pathogenic fungi
It’s hard to encapsulate a mnenomic for this.
Keanu Reeves is a men’s rights activist.
Fumigate Vincent’s house.
Cryptococcus neoformans, aspergillus fumagatum, candida albicans, histoplasma capsulatum.
Four pathogenic fungi (no prompts)
Cryptococcus neoformans, aspergillus fumagatum, candida albicans, histoplasma capsulatum.
Which fungi in this lecture is a yeast?
Cryptococcus neoformans
Which fungi in this lecture is yeast-like with myecilium-like structures
Candida albicans
Which fungi is dimorphic?
Histoplasma capsulatum
Which fungi is dimorphic?
Histoplasma capsulatum
What are risk factors for [superficial] candidosis? (no prompts)
Diabetes, immunosupressants, corticosteroids, antibiotics
What are risk factors for [superficial] candidosis? (no prompts)
Diabetes, immunosupressants, corticosteroids, antibiotics
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.
trychophyton (jock itch - tinea of the jock)
epidermaphyton,
microsporum
What are three filamentous fungi other than Aspergillus fumagatum?
(No prompts)
trychophyton (jock itch - tinea of the jock)
epidermaphyton
microsporum
Name for types of tinea - jock, foot, body, scalp.
Recall it can accrue in ya jock.
Cruris, pedis, capitis, corporis
Tinea isn’t a type of fungi. It’s…
… the word for any time of skin infection.
What is the precursor to ergosterol?
Lanosterol.
Ergesterol depletion stops fungi from replicating. What’s a bonus effect?
Stops candidal hyphae from growing.
What pharmacologically relevant effect foes ergosterol depletion have?
Reduces amphotericin binding.
What enzyme do azoles inhibit?
Cytochrome P450 3A aka 14α-demethylase.
Are azoles fungistatic or fungicidal?
Fungistatic.
What two primary drugs are used for systemic infections?
Azoles and amphotericin.
Amphotericin is the gold standard but requires close medical supervision.
Amphotericin components are structurally Gs, which are categorically a type of J.
polyenes; macrolide
What’s the significance of ergosterol to amphotericin therapy?
Amphotericin binds with great avidity to ergosterol molecules in fungal cell membranes.
What should you combine with amphotericin therapy - flucytosine or azoles?
FLUCYTOSINE - famously good synergistic effect. Absolutely do NOT combine it with azoles.
Why is amphotericin often delivered in liposomes?
Because otherwise it’s so pharmacokinetically stubborn. The liposome formulation also reduces side effects.
What are the five main headings for amphotericin unwanted effects?
Nephrotoxicity Hypokalaemia Bone marrow suppression Neurotoxicity Amphoterrible effects
What is the name of the two other polyenes?
I hate nyan cat.
Nyastatin and griseofulvin
Cons of nyastatin as opposed to amphotericin?
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).
Think mitotic interference through microtubule binding, think…
Griseofulvin
When do we use griseofulvin?
When local treatment doesn’t work. BUT has to be very prolonged.
What is 1,3-β-glucan and what fucks up it synthesis?
It’s a fungal cell wall polymeric component whose synthesis is fucked up by echinocandins.
How is flucytosine selective for fungi?
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.
What are the gentlest drugs/drug in this lecture in terms of side effects?
Flucytosine. Makes it easier to combine with for sure.
Which antifungal has problems with resistance development?
Flucytosine.
What are the big three side effects of ketoconazole? (biggest first)
Hepatotoxicity
Gynaecomastia
Interactions with metabolising enzymes
Name the three specific azoles in this lecture
Ketoconazole
Fluconazole
Itraconazole
What is basically the opposite of amphotericin when it comes to pharmacokinetics?
FLUCONAZOLE
Well absorbed orally
Even fungicidal concentrations reached in CNS, superficial mucous membranes, even skin and nails.
Are fluconazole side effects mild?
Yes. Drug interactions tho.
Bonus: nausea, vomiting, rash
Caspofungin is a …
echinocandin
Think... combination with amphotericin really poor absorption very gentle side effects problems with resistance, think...
flucytosine
nystatin’s sort of similar to saquinavir (viral protease inhibitor) in its side effects. What are they?
Nausea, vomiting, diarrhoea.
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.
GI, photophobia, headache
What are the two drugs in this lecture with potential liver toxicity?
Ketonazole, itraconozole.
