Antifungals Flashcards
subcutaneous fungi
affects muscle and conn tissue
sporothrix schenckii
Basidiobolus ranierum
Superficial fungi
dermatophytes
malassezia furfur
Primary systemic fungi
internal organs - usually start with lungs Histoplasma capsulatum Blastomyces dermatitidis Coccidioides immits Paracoccidiodes brasiliensis
Primary opportunistic fungi
internal organs candida albicans cryptococcus neoformans aspergillus fumigatus mucor/rhizopus pneumocystis jirovecii
Cell wall synthesis inhibitors
Echinocandins
inhibit Glucan synthesis
Cell membrane synthesis inhibitors
Polyene, Azoles
Ergosterol synthesis
DNA/RNA synthesis inhibitor
Flucytosinnnne
Pyrimidine analogues
An optimal antifungal will have
Wide spectrum of activity favorable bioavailability adequate in vivo efficacy high therapeutic index low cost
Polyenes
bind ergosterol in fungal cell membrane, form pore and leads to leaky membrane
have large lactone ring with conjugated double bonds and two sides - lipophilic and hydrophilic side
unstable when taken orally
examples of polyenes
Amphotericin B
Nystatin
In vitro, for polyenes, antifungal activity correlates with
number of double bonds
at high concentration, polyenes are fungasidal
unstable orally taken
Resistance mechanism against Polyenes
If fungi lowers ergosterol in cell membrane, then polyenes can’t bind
Amphotericin B
produced by Streptomyces nodosus
‘Ampho terrible’
leakage of Na, K and Ca
not sure how differentiates between human and fungi cell
Broad spectrum - fungicidal
for severe to life threatening fungal infections
IV administration only
Toxicity of Amphotericin B
Nephrotoxic
constricts efferent arterioles
wastes Mg and bicarb
disrupts Erythropoietin and leads to anemia
Pharmacokinetics of Amphotericin B
Poorly absorbed from GI
given by IV injection with deoxycholate - bile lipid
90% bound to serum proteins
Hepatic metabolism and renal excretion - slow about 15 days
Acute adverse effects of Amphotericin B
chill, fever and vomiting
binds host cell (cholesterol) with a lesser affinity leads to toxicity
Pain at site of injection
chronic adverse effects of Amphotericin B
nephrotoxicity
Nystatin
made by streptomyces noursei
Polyene
topical for local infection
poor bioavailability
No’s for Nystatin?
No IV infusion
No drug interactions
No significant side effects
what would you give Nystatin for?
Oral thrush
Swish and swallow
Azoles
class of drugs composed of 5 membered azole ring containing at least one non carbon atom classified according to number of nitrogens Largest group
Azoles activity
associated with broad spectrum (superifical to systemic)
can give orally, IV, IM and topically
Mechanism of Azoles
inhibits ergosterl synthesis by inhibiting Lanosterol conversion to ergosterol
What can Azoles potentiate?
Cyclosporin
Phynetoin
Warfarin
Isoniazide
