11 Fungal diseases and antifungals Flashcards
what is the target of action for polyenes
ergosterol- binds and destabilises plasma membranes
what is the target of action for azoles
the enzyme lanosterol
what is the target of action for allylamines
the enzyme squalene epoxide
what is the target of action for echinocandins
glucan- in the cell wall, diminished= weakened cell wall
what is the target of action for 5-Flucytosine
nucleic acids
name 5 groups of antifungals
polyenes, azoles, allylamines, echinocandins, 5-Flucytosine
which 3 groups of antifungals directly or indirectly affect ergosterol in plasma membrane
polyenes, azoles and allylamines
how to achieve selective toxicity (2)
topical application and target specificity
e.g. try to change structure of azoles so bind stronger to fungal enzymes and not humans
selective toxicity problems
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
describe acute reactions due to Amphotericin B toxicity and how to approach this
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
describe renal toxicity associated with Amphotericin B
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
what has been done to try and work around AmB toxicity (3)
changing the delivery, making vesicles (liposomal AmB), disc shapes (AmB colloidal dispersion) and long ribbons (AmB lipid complexes)
explain how changing the delivery of AmB decreases it’s toxicity
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
possible issues with changing the delivery of AmB
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
why still try use AmB if it’s toxic
because it’s so effective and has a good spectrum of activity
describe antifungal resistance in relation to AmB, azoles and 5-Flucytosine
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)
what enzyme do echinocandins target and what does it make
b-1,3-D-glucan synthase- makes glucan which makes cell wall
what are mycoses
disease caused by fungal infection
give 3 examples of superficial mycoses
skin= dermatophytosis
nails= onychomycosis
mucous membranes= candidiasis
give 3 examples of deep mycoses acquired in the UK
invasive candidiasis
aspergillosis
crytococcosis
define dermatophytosis
fungal skin infection
what is tinea pedis, what topical treatment is used and what does it predispose
dermatophytosis of the foot- athletes foot, topical terbinafine
predisposition to cellulitis- broken skin is portal of entry for strep/staph
what is cellulitis
bacterial infection of deeper layers of skin
what is tinea corporis and what topical treatment is used
fungal infection on the body- ring like appearance
topical clotrimazole
medical name for dandruff and how to treat
Seborrheic dermatitis
medicated shampoo- nizorale
what is onychomycosis
fungal infection of the nail
treatment for onychomycosis
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)
give 3 common reasons for oral thrush
bad steroid inhaler technique
bad denture hygiene
antibiotic course changing organisms in mouth
treatment for oral thrush
topical nystatin, 1ml 4 times a day for a week
oral fluconazole if immunosuppressed
what fungus caused oral thrush
candida
describe how invasive candidiasis develops in immunosuppressed patients
in mouth anyway, in cancer chemo epithelial protection breaks down, goes into blood stream, neutropenic so can’t fight it off
describe aspergillosis
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
what’s main treatment for aspergillosis
azoles
what can crytococcus cause
meningitis in HIV
main treatment for crytococcus
AmB
which antifungal acts by inhibiting cell wall synthesis
caspofungin
