11 Fungal diseases and antifungals

Question 1

what is the target of action for polyenes

Answer 1

ergosterol- binds and destabilises plasma membranes

Question 2

what is the target of action for azoles

Answer 2

the enzyme lanosterol

Question 3

what is the target of action for allylamines

Answer 3

the enzyme squalene epoxide

Question 4

what is the target of action for echinocandins

Answer 4

glucan- in the cell wall, diminished= weakened cell wall

Question 5

what is the target of action for 5-Flucytosine

Answer 5

nucleic acids

Question 6

name 5 groups of antifungals

Answer 6

polyenes, azoles, allylamines, echinocandins, 5-Flucytosine

Question 7

which 3 groups of antifungals directly or indirectly affect ergosterol in plasma membrane

Answer 7

polyenes, azoles and allylamines

Question 8

how to achieve selective toxicity (2)

Answer 8

topical application and target specificity

e.g. try to change structure of azoles so bind stronger to fungal enzymes and not humans

Question 9

selective toxicity problems

Answer 9

we have cholesterol in our plasma membranes, antifungals which bind to ergosterol can also bind to our cholesterol
azoles that bind to fungal cytochrome enzymes can also bind to humans

Question 10

describe acute reactions due to Amphotericin B toxicity and how to approach this

Answer 10

30 mins post infusion
chills, fever, shortness of breath, drop in BP, aches
peak 30 mins later and lasts 4 hours
due to induction of prostaglandin E2
do a test dose and then gradually increase
pre-medicate with paracetamol, brufen or steroids

Question 11

describe renal toxicity associated with Amphotericin B

Answer 11

when taken for a while most people get renal effects to different degrees of severity
vasoconstricts afferent renal arterioles, less blood delivered to glomeruli
affects renal tubules, leak K, mg and electrolytes
decreased erythropoietin production
can lose entire nephron units, entire GFR drops

Question 12

what has been done to try and work around AmB toxicity (3)

Answer 12

changing the delivery, making vesicles (liposomal AmB), disc shapes (AmB colloidal dispersion) and long ribbons (AmB lipid complexes)

Question 13

explain how changing the delivery of AmB decreases it’s toxicity

Answer 13

less AmB floating around to go into kidney and cause toxicity
idea that when it’s passed through infection, it breaks down and AmB free to work- localising antimicrobial effects
ribbon= filtered out in spleen and liver so useful when the infection is there, not so much if in CNS since can’t pass BBB

Question 14

possible issues with changing the delivery of AmB

Answer 14

have to dose differently to get enough of the drug in the system, can lead to problems because if preparations are confused then can cause death
expensive

Question 15

why still try use AmB if it’s toxic

Answer 15

because it’s so effective and has a good spectrum of activity

Question 16

describe antifungal resistance in relation to AmB, azoles and 5-Flucytosine

Answer 16

for a fungal cell to become resistant to AmB it needs to mutate ergosterol, but fungi that do this become less pathogenic
however, proteins can mutate so increasing azole resistance
for 5-F resistance happens quickly in monotherapy, but rare in combination therapy (combined with a drug that targets plasma membrane)

Question 17

what enzyme do echinocandins target and what does it make

Answer 17

b-1,3-D-glucan synthase- makes glucan which makes cell wall

Question 18

what are mycoses

Answer 18

disease caused by fungal infection

Question 19

give 3 examples of superficial mycoses

Answer 19

skin= dermatophytosis
nails= onychomycosis
mucous membranes= candidiasis

Question 20

give 3 examples of deep mycoses acquired in the UK

Answer 20

invasive candidiasis
aspergillosis
crytococcosis

Question 21

define dermatophytosis

Answer 21

fungal skin infection

Question 22

what is tinea pedis, what topical treatment is used and what does it predispose

Answer 22

dermatophytosis of the foot- athletes foot, topical terbinafine
predisposition to cellulitis- broken skin is portal of entry for strep/staph

Question 23

what is cellulitis

Answer 23

bacterial infection of deeper layers of skin

Question 24

what is tinea corporis and what topical treatment is used

Answer 24

fungal infection on the body- ring like appearance

topical clotrimazole

Question 25

medical name for dandruff and how to treat

Answer 25

Seborrheic dermatitis

medicated shampoo- nizorale

Question 26

what is onychomycosis

Answer 26

fungal infection of the nail

Question 27

treatment for onychomycosis

Answer 27

topical or systemic terbinafine
in early stages can get amrolifine preparations, scrape nail and rub this oily substance on, seeps in and kills fungus
systemic terbinafine= tablets, keeps fungus at bay in new developing nail, grows and push infected nail out, takes long time (months)

Question 28

give 3 common reasons for oral thrush

Answer 28

bad steroid inhaler technique
bad denture hygiene
antibiotic course changing organisms in mouth

Question 29

treatment for oral thrush

Answer 29

topical nystatin, 1ml 4 times a day for a week

oral fluconazole if immunosuppressed

Question 30

what fungus caused oral thrush

Answer 30

candida

Question 31

describe how invasive candidiasis develops in immunosuppressed patients

Answer 31

in mouth anyway, in cancer chemo epithelial protection breaks down, goes into blood stream, neutropenic so can’t fight it off

Question 32

describe aspergillosis

Answer 32

A lives in environment, digging up vegetation spurs up spores of aspergillus, normal defences in lungs waft away spores
in structurally abnormal (e.g. cavity of previous disease), it lands and grows wall of fungus, can break off and travel in blood stream

Question 33

what’s main treatment for aspergillosis

Answer 33

azoles

Question 34

what can crytococcus cause

Answer 34

meningitis in HIV

Question 35

main treatment for crytococcus

Answer 35

AmB

Question 36

which antifungal acts by inhibiting cell wall synthesis

Answer 36

caspofungin