anti fungals Flashcards
what are some key characteristics of fungi?
- cells contain nuclei like chromosomes (unlike bacteria)
- they cannot photosynthesis (they are heterotrophic, like animals)
- hyphae are key to growth (exude enzymes and absorb food)
- spores are important for reproduction (sexual and asexual)
what type of cell are fungi?
how do they reproduce ?
- they are single cells/ complex filamentous networks
- ‘dimorphic’ switching between Yeats and filaments
- sexual or asexual reproduction
- highly adaptable to their new environment
what are the key differences between fungi and bacteria?
- fungal walls contain polysaccharide not found in other micro-organisms
- CHITIN = this adds rigidity and support, this confers resistance to cell wall antibiotics (eg- penicillin)
- B- glucan = site of action of some anti fungals
- cell membranes consist of ergosterol rather than cholesterol (this is a good target for some anti funagls)
why will antibiotics not work against fungus?
because of the chitin protein in the cell wall - adding support and rigidity.
what type of pathogen are fungals
they are opportunistic pathogens - this means that they will target immunocompromised people
what fungus is going to cause superficial mycoses?
malassezia furfur
what fungus Is going to cause cutaneous mycoses?
- tinea capitus
- tinea cruris
- tinea pedis
what fungal pathogens are able to induce disease of an immunocompetent host?
- histoplasmosis
- coccoidomycosis
due to what, will most ‘opportunistic pathogens’ cause systemic disease in patients with compromised cell mediated immunity due to:
- HIV
- immunosuppressive medication
- concurrent illnesses/long term lines.
what type of yeast will cause meningitis
crytococcus neoformans
yeast?
single oval cells replicate by BUDDING or FISSION
(some are dimorphic, can be filamentous too)
disease entity:
candida spp.
thrush, fungaemia
disease entity:
cryptococcus neoformans
meningitis
pneumonia
fungaemia
disease entity:
systemic Yeasts
pulmonary or disseminated infections
disease entity:
aspergillus spp., mucor, rhizopius, absidia.
- allergic bronchopulmonary aspergillosis
- aspergilloma
- invasive aspergillois
disease entity:
dermatophytes; epidermophyton, microsporum, trichophyton
chronic infection of skin and nails, kerion
what are the 6 anti fungal drugs
- azoles
- terbinafine
- polyenes
- flucytosine
- griseofulvin
describe the ergosterol biosynthetic pathway?
- selective toxicity= key principle underpinning anti-infective therapy
- ergosterol biosynthetic pathway is essential to fungal but not to eukaryotic cell membranes
- anti fungal drugs can exhibit inhibitory mechanisms on ergosterol synthesis
what 2 drugs will act as ergosterol inhibitors?
azoles
terbinafine
describe the mechanism of action of Fluconazole
- it will inhibit fungal cytochrome P450 enzyme 14a-demethylase
- prevents conversion of lanosterol to ergosterol
- primarily fungistatic (prevents growth)
- will need a high dose to be fungicidal
what are 4 specific try-azole drugs ?
- fluconazole
- itraconazole
- voriconazole
- posaconazole
fluconazole
- well absorbed after oral administration
- good penetration into the cerebrospinal fluid to treat neurological infection
- excreted largely unchanged in the urine so can be used to treat candiduria.
itraconazole?
- capsules require an acid environment in the stomach for optimal absorption
- hepatotoxic
- issues with drug to drug interaction
voriconazole
complex issues with drug to drug interaction
posaconazole
lisensed for the treatment of invasive fungal infections unresponsive to conventional treatment
what enzyme will terbinafine
squalene epoxidase
terbinafine:
indications?
dermatophyte infections of the nails, ringworm infections, where oral therapy is appropriate.
terbinfine:
cautions?
psoriasis, autoimmune disease
terbinafine:
hepatic/renal impairment?
manufacturer advises avoid in liver disease - elimination reduced.
- use half the normal dose if eGFR is less than 50mL/minute/1.73m2 and no suitable alternative is available.
terbinafine:
pregnancy and breast feeding?
- only use in pregnancy if potential benefit outweighs the risk
- avoid in breast feeding as present in milk
Polyenes:
mechanism of action?
amphotercin B binds with ergosterol in fungal cell membranes, pores form which cause rapid leakage of monovalent ions and fungal cell death.
describe the use/action of polyenes?
- not absorbed well when given by mouth
- nystatin is applied locally for oral, oropharyngeal and peri oral infections.
- amphotercin B by intravenous fusion is used to treat systemic fungal infections and is active against most fungi
- it is highly protein bound and penetrates poorly into tissues
- amphotercin B is toxic and side effects are common
- less toxic than Ampotericin B liposomal formulations are increasingly used
Flucytosine indications
systemic yeast and fungal infections, often as an adjunct to amphotericin B
how does flucytosine work?
it disrupts the replication of dna by interfering with the nucleic acid chain as a false nuceltide.
but it is non selective so it will also do this to the host cells.
renal impairment for flucytosine
reduce the dose in case of renal impairment and measure the drug concentration.
pregnancy and breast feeding indications for flucytosine?
avoid in breast feeding
teratogenic in animal studies, only use if potential benefits outweigh the risks.
what are the side effects for flucytosine?
hepatoxicity
blood disorders
mechanism of echinocandins?
examples?
examples = andifulafungin, caspofungin, micafungin
- they act by inhibiting beta -(1,3)-D-glucan synthase.
- fungicidal against candida spp.
- fungistatic against aspergillum spp. but are not used for the treatment of aspergillosis
- not effective against fungal infections of the CNS
- CAN ONLY BE GIVEN INTRAVENOUSLY
griseofulvin indications
dermatophyte infections of the skin, scalp, hair and nails where topical therapy has failed
griseofulvin cautions
may pair perofmrnace of skilled tasks, the effects of alcohol will be enhanced.
griseofulvin contra indications
avoid in severe liver disease
griseofulvin pregnancy and breast feeding
avoid!!!!!
side effects of griseofulvin
nausea, vomitting, diarrhoea, headache, glossitis
summary: mode of action
tri-azoles
blocks P450 and sterol 14 alpha demthylase in the cell wall
summary: mode of action
terbinafine
inhibits squalene epoxidase that accumulates toxic steroid in the cell wall
summary: mode of action
polyenes
inhibits form pores in funga membrane
summary: mode of action
flucytosine
inhibits protein synthesis
summary: mode of action
echinocandins
inhibits 1,3 beta glucan in cell wall polysaccharide
summary: mode of action
griseofulvin
inhibits fungal mitosis (induces hepatic CYP450)
