Anti-fungals (year 2)

Question 1

Is Malassezia commensal or pathogenic?

Answer 1

commensal

Question 2

what needs to happen for Malassezia to cause disease?

Answer 2

reduction in normal cutaneous barrier function/immune function

Question 3

is dermatophytosis commensal or pathogenic?

Answer 3

pathogenic

Question 4

what are some reason antifungals may fail? (4)

Answer 4

fungal cell wall and capsules
toxicity (fungi are eukaryotes)
poor penetration
not treating beyond cure

Question 5

what are fungal cell walls made of? (3)

Answer 5

glycoprotein
glucan
chitin

Question 6

why are fungal cell walls good targets for treatment?

Answer 6

mammalian cells lack a cell wall (limited toxicity)

Question 7

what is the main sterol in fungal cell membranes?

Answer 7

ergosterol

Question 8

what drugs groups target ergosterol? (3)

Answer 8

polyenes
azoles
allylamine

Question 9

what type of protein is the enzyme that synthesises ergosterol from lanosterol?

Answer 9

cytochrome P450

Question 10

where are cytochrome P450 enzymes found in the body?

Answer 10

most tissues (especially liver)

Question 11

what is the major function of cytochrome P450 enzymes?

Answer 11

drug metabolism

Question 12

what are the most common anti-fungal drug groups? (2)

Answer 12

azoles

allylamines

Question 13

what do azoles target?

Answer 13

cytochrome P450 enzyme

Question 14

what do azoles prevent the formation of? (what’s formed instead?)

Answer 14

ergosterols

toxic sterols

Question 15

are azoles narrow or broad spectrum?

Answer 15

broad

Question 16

what can decrease the absorption of azoles?

Answer 16

decrease acid environment (antacids)

Question 17

what can increase the absorption of azoles?

Answer 17

giving with food (fatty)

Question 18

how are azoles circulated around the body?

Answer 18

highly protein bound (albumin)

Question 19

what are the two groups of azoles?

Answer 19

triazoles

imidazoles

Question 20

what are some examples of triazoles? (4)

Answer 20

itraconazole
fluconazole
voriconazole
posaconazole

Question 21

what are some examples of imidazoles? (4)

Answer 21

ketoconazole
miconazole
enilconazole
clotrimazole

Question 22

what has the addition of the triazole ring allowed? (4)

Answer 22

higher specificity for the fungal cytochrome P450
increased affinity for fungal cell membranes
lipophilic
keratophilic

Question 23

where are azoles metabolised?

Answer 23

liver

Question 24

where are azoles mainly excreted?

Answer 24

bile

Question 25

what is the most common side effect of azoles?

Answer 25

hepatotoxicity

Question 26

what are some other side effects of azoles? (other than hepatotoxicity)

Answer 26

``` anorexia, vomiting, diarrhoea thrombocytopenia teratogenic hormone suppression vasculitis ```

Question 27

what are some examples of medications that will decrease the absorption of azoles? (3)

Answer 27

H2 blockers antacids anticholinergics

Question 28

what do allylamines inhibit?

Answer 28

squalene epoxidase

Question 29

what do allylamines prevent the formation of?

Answer 29

lanesterol

Question 30

how are allylamines transported in blood?

Answer 30

highly protein bound

Question 31

where are allylamines metabolised?

Answer 31

liver

Question 32

where are allylamines excreted?

Answer 32

urine

Question 33

what are the side effects of allylamines?

Answer 33

(uncommon) GI signs hepatotoxicity

Question 34

what does polyene antibiotic target?

Answer 34

ergosterol

Question 35

how do polyene antibiotics work?

Answer 35

insert into the fungal cell membrane causing it to become leaky

Question 36

what is an example of a polyene antibiotic?

Answer 36

amphotericin B

Question 37

what does whether an anti-fungal in fungicidal or fungistatic depend on?

Answer 37

the dose

Question 38

what are the main side effect of amphotericin B?

Answer 38

nephrotoxicity

Question 39

what does griseofulvin effect?

Answer 39

interferes with microtubule formation

Question 40

what are the side effects of griseofulvin?

Answer 40

tertatogenic hepatotoxic (idiosyncratic toxicity in cats) GI issues carcinogenic