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Pharm-Mycotic dz
pharm
43
Veterinary Medicine
Undergraduate 3
05/25/2012

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Term
fungal dz = 2 broad categories:
Definition
dermatophytes (skin)
internal dz (aspergillus)
Term
most antimycotics TI =
Definition
low -fairly toxic
Term
most antimycotics actions are...
Definition
...fungistatic
Term
dermatophyte infections should be tx...
Definition
...systemically (topical tx is rarely sufficient)
Term
antigungal anitbiotics =
Definition
polyenes
griseofulvin
Term
azoles =
Definition
ketoconazole
itraconazole
Term
tx of yeast infections with...
Definition
...flucytosine
Term
fungal sterol synth is imp for...
Definition
...mb integritiy and fluidity
Term
unique pathway antimycotics target =
Definition
fungal sterol synth
Term
give 2 examples of polyenes
Definition
amphotericin B
nystatin
Term
admin polyenes as...
Definition
...colloid suspension or dissolved in mild detergent (as nearly water insoluble)
Term
polyene structure means its...
Definition
...amphipathic - hydrophobic and hydrophilic ends)
Term
polyene structure means its...
Definition
...amphipathic - hydrophobic and hydrophilic ends)
Term
mech of polyenes =
Definition
Interacts with egosterol in call mb = forms a pore = allows ions through and leak ATP
Term
polyene absorption via gut =
Definition
poor
Term
tx of GI mycoses with polyenes admin...
Definition
...orally
Term
systemic tx with polyenes admin...
Definition
...IV
Term
plasma half life of poleyene =
Definition
long as polyenesa re highly plasma bound (due to lipophilic nature of polyenes)
Term
clinical use of polyenes =
Definition
wide spectrum of activity including aspergillus and candida

for immunocompromised patients may need to give long term whuch may result in toxicity :(
Term
toxicity of propylene =
Definition
slow toxicity, usually renal - tubular necrosis and renal failure

Infusion related fever but v rare
Term
mech of greisofulvin =
Definition
unclear
inhibits nucleic acid synth and mitosis and microtubule formation in some way
Term
is griseofulvin water soluble?
Definition
v poorly
Term
is griseofulvin fat soluble?
Definition
quite = absorption enahnced if given with fatty foods
Term
griseofulvin is metab by...
Definition
...live
Term
griseofulvin distribution =
Definition
gd

depo in newly formed skin where it binds to keratin in the stratus corneum
Term
linical use of griseofulvin
Definition
tx of dermatomycoses

skin becomes resisitant to further fungal growth and as new skin and hair grow and replace old the infection gradually disappears. takes ~6wks
Term
if stop tx with griseofulvin b4 6wks=
Definition
reinfection (as drug only fungistatic)
Term
toxicity of griseofulvin
Definition
rare- relatively safe and qu commonly used

1.allergies
2.drug interactions eg with warfarin = decr anticoagulant effect
with phenobarbitone = incr griseofulvin metab
3. teratogenesis
Term
Azoles, give three examples
Definition
ketoconazole
imidazole
triazole
Term
mech of azoles =
Definition
inhibit laosterol 14-demethylase synth by inhibiting cytochrome p450 = accum of lanosterol and decr ergosterol = change perm and fluidity of cells mb
Term
action of azole =
Definition
fungistatic excpet at high concnetrations
Term
toxicity of azoles =
Definition
relatively non toxis :)
1. mainly GIT upsets (V and D)
2. ketoconazole effects mammalian cytochrom o450 (responisble for drug metab and steroid synth so ketoconazole can incr duration of other drugs)
Term
ketonconazole can be used to tx
Definition
cushings dz
Term
clinical use of azoles =
Definition
-broad spectrum
-systemic or topically
useful in face of polyene resistance
not v effective against yeast
Term
flucytosine works specifically against..
Definition
...yeast (no fungi activity)
Term
flucystosine (5-FU) is an analogue of...
Definition
...nucleotide
Term
id 5-FU water sol?
Definition
highly!
Term
mech of flucytosine =
Definition
taken up by yeast cells via cytosine permease (specific mech to yeast)

flucytosine is converted to 5-FU then fUMP then fUTP

fUMP inhibits RNA synth
fUTP inhibits DNA synth
Term
flucytosine is synergistic with...
Definition
...amphotercin B (as amphotercin B incr cell perm = incr uptake of flucytosine)
Term
admin of flucystosine =
Definition
oral (well absorbed)
Term
distribution of flucytosine =
Definition
widespread, goes into CSF = gd for intracranial infections
Term
resistance to flucytosine =
Definition
rapid :( therfore give with amphotercin B
Term
toxicity of flucytosine =
Definition
BM supression due to antineoplastic action of other metabolites of the drug (target rapidly dividing cells)=thrombocytopaenia, leukopaenia, anameia

overcome by lowing doses by co-admin with amphotericin B
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