Anti-fungals (year 2) Flashcards
Is Malassezia commensal or pathogenic?
commensal
what needs to happen for Malassezia to cause disease?
reduction in normal cutaneous barrier function/immune function
is dermatophytosis commensal or pathogenic?
pathogenic
what are some reason antifungals may fail? (4)
fungal cell wall and capsules
toxicity (fungi are eukaryotes)
poor penetration
not treating beyond cure
what are fungal cell walls made of? (3)
glycoprotein
glucan
chitin
why are fungal cell walls good targets for treatment?
mammalian cells lack a cell wall (limited toxicity)
what is the main sterol in fungal cell membranes?
ergosterol
what drugs groups target ergosterol? (3)
polyenes
azoles
allylamine
what type of protein is the enzyme that synthesises ergosterol from lanosterol?
cytochrome P450
where are cytochrome P450 enzymes found in the body?
most tissues (especially liver)
what is the major function of cytochrome P450 enzymes?
drug metabolism
what are the most common anti-fungal drug groups? (2)
azoles
allylamines
what do azoles target?
cytochrome P450 enzyme
what do azoles prevent the formation of? (what’s formed instead?)
ergosterols
toxic sterols
are azoles narrow or broad spectrum?
broad
what can decrease the absorption of azoles?
decrease acid environment (antacids)
what can increase the absorption of azoles?
giving with food (fatty)
how are azoles circulated around the body?
highly protein bound (albumin)
what are the two groups of azoles?
triazoles
imidazoles
what are some examples of triazoles? (4)
itraconazole
fluconazole
voriconazole
posaconazole
what are some examples of imidazoles? (4)
ketoconazole
miconazole
enilconazole
clotrimazole
what has the addition of the triazole ring allowed? (4)
higher specificity for the fungal cytochrome P450
increased affinity for fungal cell membranes
lipophilic
keratophilic
where are azoles metabolised?
liver
where are azoles mainly excreted?
bile
what is the most common side effect of azoles?
hepatotoxicity
what are some other side effects of azoles? (other than hepatotoxicity)
anorexia, vomiting, diarrhoea thrombocytopenia teratogenic hormone suppression vasculitis
what are some examples of medications that will decrease the absorption of azoles? (3)
H2 blockers
antacids
anticholinergics
what do allylamines inhibit?
squalene epoxidase
what do allylamines prevent the formation of?
lanesterol
how are allylamines transported in blood?
highly protein bound
where are allylamines metabolised?
liver
where are allylamines excreted?
urine
what are the side effects of allylamines?
(uncommon)
GI signs
hepatotoxicity
what does polyene antibiotic target?
ergosterol
how do polyene antibiotics work?
insert into the fungal cell membrane causing it to become leaky
what is an example of a polyene antibiotic?
amphotericin B
what does whether an anti-fungal in fungicidal or fungistatic depend on?
the dose
what are the main side effect of amphotericin B?
nephrotoxicity
what does griseofulvin effect?
interferes with microtubule formation
what are the side effects of griseofulvin?
tertatogenic
hepatotoxic (idiosyncratic toxicity in cats)
GI issues
carcinogenic
