Antifungals Flashcards
polyenes
natural compounds - wide spectrum
form a pore structure which allows cations to leak out - K+, Na+
polyenes are a subgroup of
macrolides
examples of polyenes
Ampheterin B - Iv old
nystatin - oral - yeast infections in the mouth and stomach
polyenes associate with
ergosterol
nyastatin
oral/stomach yeast infections
- not absorbed into the blood stream, won’t treat fungal infections in other parts of the body or skin
Am B x10 more
specific for ergosterol than cholesterol
polyenes are typically obtained from
streptomycin bacteria
polyenes feature and treat
features large cyclic ester ring and are used to treat mild thrush
Ampheterin B - produced by, development,
streptomyces nodosus
- development of lipid based formulation, hydrophilic which has enhanced the ability to limit toxicities
resistant to polyenes
Candida Lusitania
aspergillus terres and trichophyton
Ampheterin B is normally combined with …
deoxycholate
-permits IV administration
AmB general
poor absorption into the CSF
can also be used topically - GI, urinary infection
Azores - strusture
- largest group of antifungals
- 5 approved for systemic infections
- 5 membered heterocyclic ring - 1 or more N/O/S atom
imidiazole
2N atoms
rarely used
toxicity and specificity problems\
voriconazole
methyl group allows activity against aspergillus
Azoles action
inhibit 14a sterol demethylase - blocks in the heme ion in the enzyme - fungistatic
block - iansterol –> eburicol
issues with azoles
drug interactions - they are metabolised by cytochrome P450 enzymes in the liver
resistance
what do azoles not treat
aspergillus - except voriconazole (methlgroup)
which enzyme do azole inhibit
CYP3A4
which drug should care be take when azalea are administered with
rifampicin - another drug which is metabolised by CYP3A4 - build up
what are azaleas the initial choice for
rapidly progressing severe systemic infections
histoplasma and blastomycosis
alzoles
what resistance to azoles
protein phosphatase calcineurin allows survival during membrane stress by azoles
achieves greater levels in CNA in patients with dissemination infections
voriconozole
Allylamine
synthetic compounds, inhibit ergosterol synthesis - inhibit squalene epoxidase
squalene accumulates in the cell which is toxic to the cell
allylamines are active against
dermatophytes
allylamines are poorly active against
candida, aspergillus and cryptococcus neoformins
example of a allylamine -
terbinafine
terbinafine
inhibits onchomycosis - tine ungium - nails
inhibits squalene epoxidase
topical or oral tablet
proven efficacy at penetrating kerinized tissues
no effect on human sterol synthesis
highly lipophilic - high nail, sebum conc.
terbifinafine is a potent inhibitor of which enzyme
CYP2D6
topical Allylamine
naftifine
what would you use to treat systemic aspergillosis
terbinafine and intraconazole together
