Antifungals Flashcards
3 forms of fungi
Filamentous fungi
Yeasts
dimorphic- either year or filamentous fungi
what distinctive features do filamentous fungi have
hair like hyphae
mycelium which holds hyphae together
septae
produce spores
what distinctive feature do yeasts have
divide by budding
Antifungal targets
cell membrane- ergesterol
cell wall- B 1,3 glucan.
Are fungi prokaryotic or eukaryotic
eukaryotic
function of ergesterol
regulate membrane permeability.
mechanism of egesterol synthesis.
Squalene is converted to lansterol which is converted to ergesterol.
• Ist conversion requires enzyme squalene epoxidase
• 2nd conversion requires enzyme Lanosterol 14a demethylase.
what part of a fungi is ergesterol part of
cell membrane
what part of a fungi is B1, 3 glucans part of
cell wall.
what are the 4 main anti fungal classes
Polyenes
Allyamines
Azoles
Echinocandins.
what is the mode of action of polyenes
– Association with ergosterol- binds to it.
– Formation of pore-like molecular aggregates
Main examples of polyenes
Amphotericin B
lipid associated Amphotericin B
Nystatin
side effects of Amphotericin B
Nephrotoxicity
allergic reactions
Why is lipid amphotercin better than normal amphotericin b
• Minimize delivery of AmB to kidney cells- more selective toxicity.
redeuced nephroroxicity.
How is nystatin prescribed
parenterally.
How is amphotericin b prescribed
parenterally.
What is the mode of action of allyamines
inhibit egosterol synthesis
acts on squalene epoxidase.
Example of allyamines
Terbinafine
Is amphotericin broad or narrow spectrum
broad
Are allyamines broad or narrow spectrum
broad
What are the side effects of allylamines
liver toxicity.
clinical use of allyamines
Dermatophyte infections (superficial fungal infections)-caused by fungi which like to eat keratin.
What conditions are allyamines used for
• Topical use
– Athletes foot , fungal groin infection, (tinea pedis), tinea corporis, tinea cruris.
• Systemic (oral) use
– Scalp ringworm, nail fungal infection (tinea capitis), onychomycosis
what are the 2 types of azoles.
Imidazole- toxic
Triazole- non toxic
how many nitrogen atoms sides imidazole have
2
how many nitrogen atoms do triazoles have
3
What is the mode of action of azoles
• Mode of action
– Inhibit ergosterol synthesis
Lanosterol 14α-demethylase
Are azoles broad or narrow spectrum
depends on drug but mainly broad
which is the only azole which does;t work against Aspergillus
Fluconazole.
Most commonly used imidazole
Clotrimazole- vaginal thrush
Most commonly used Triazoles
Fluconazole
Itraconazole
Voriconazole.
What are the side effects of azoles
hepatotoxicity- mild liver enzyme abnormalities.
what drugs do azoles commonly interact with
Inhibit cytochrome P450 enzymes.
what are type of infections are imidozoles used for
superficial infections
What type of infections are triazoles used for
severe fungal infections
What is the mode of action of Echinocandins
Inhibition of β-1,3-glucan synthase
Most commonly used Echinocandins
Anidulafungin
Are echinocandins broad or narrow spectrum
broad- although it misses out cryptococcus.
What are the side effects of enchinocandins
Minimal effects
skin rash, nausea, vomiting, headache, diarrhoea in common with any other drug
Clincial use of enchicandins
Systemic infections
what type of drug is 5-fluorocytosine (5-FC)
Synthetic analogue of cytosine
What is the mode of action of 5-fluorocytosine (5-FC)
Entry into cell requires fungal cytosine perm ease.
• Inhibit RNA/protein synthesis and DNA synthesis
What spectrum of fungi does 5-fluorocytosine (5-FC) act against.
Yeasts only
What are the side effects of 5-fluorocytosine (5-FC
Bone marrow suppression
Clinical use of 5-fluorocytosine (5-FC)
Limited
Cryptococcal meningitis
What are the reasons for therapeutic drug monitoring
to minimize efficacy
to minimize toxicity
what 3 drugs are therapeutically monitored
Itraconazole
5-fluorocytosine
Voriconazole.
