usually opportunistic, so often seen in cases of dec immunity
what are dermatophytoses?
fungal infection of the skin
what are the DIFFERENCES between fungi cells and animal cells? (3)
(1) DNA- animal is diploid, fungi are haploid (one set of chromosomes) (2) CELL WALL- animal cells don't have one, fungi cell walls are made of chitin, mannans, glucans. (3) CELL MEMBRANE- animal is mostly cholesterol, Fungi is mostly ergosterol
amphotericin, echinocandins, azoles, griseofulvin, flucytosine, terbinafine/naftifine/amorolfine(allylamines)... say what each of these works on
membrane, cell wall, inhibit formation of ergosterol out of lanosterol, microtubules, DNA, squalene-->lanosterol (which then can't proceed to ergosterol)
intracellular--> pyrimidine analogues/ thymidylate synthase inhibitors--> which drug is here?
intracellular--> mitotic inhibitors--> which drug is here?
what are the naturally occuring antifungal antibiotics? (3 categories)
*polyene antibiotics--> which in this category, and the specific MOA?
amphotericin B, natamycin, nystatin. The polyenes are able to form pores in the cell membrane which leads to gross disturbances in electrolyte balance
*what is the order of type of cells, for most to least affinity, of polyenes?
fungi>protozoa>mammalian cells>bacteria (fungi pizza--> my belly)
*spectrum of polyenes?
*what are polyenes the gold standard for?
*amphotericin B can enhance what other drug?
enhances the antifungal effect of flucytosine (BB has the flu :( )
*what can you say about amphotericin B and oral administration?
poorly absorbed oral admin. This could be good if treating upper GI infections- poor absorbption so stays in GI and fights fungi (Bad oral absorption)
*what can you say about amphotericin B and IV administration?
*SLOW* IV INFUSION! or it can be complexed with with liposomes or other lipid containing preparations (slow renal excretion, slow IV infusion...what a slowpoke)
*what is the protein binding of amphotericin B like?
HIGHLY protein bound (B for BOUND)
*what is the tissue penetration of amphotericin? exceptions?
usually there is POOR tissue penetration because of the high protein binding, EXCEPT if the tissue is inflamed, the barrier is compromised and the protein bound drug can get in
*what is the excretion of amphotericin B like?
VERY SLOW RENAL EXCRETION (>2mo) (hence, renal toxicity. I guess it only got a "B" in excretion class because of this)
*what are the unwanted effects of amphotericin B? (3)
(1) RENAL TOX (reversible) (2) hypokalemia- (can help with potassium chloride supplement) (3) irritant to endothelium (vomiting, chills, fever) (AMP energy makes me pee like I have renal toxicity, and then I pee out all the potassium from my endothelium)
*how can you make it so there is less unwanted effects of amphotericin B?
liposome-, lipid complexed preparations show less side effects
*WHERE are nystatin and natamycin not absorbed?
skin and mucous membranes (so...can put inside of vagina and it wont go systemically, will just stay in there and kill the yeast)
*what are nystatin and natamycin used to treat?
ONLY localized superficial infections
*side effects of nystatin and natamycin?
vomiting and diarrhea (nystatin goes in the vag and its side effects are VD.....lol)
what kinda fungi are nystatin and natamysin good against?
key notes of polyenes (5) (systemic, or local? broad or narrow? MOA? side effect?)
1. Amphotericin B: systemic and local 2. Natamycin and nystatin: local 3. Broad spectrum fungicidal drugs 4. Binding to ergosterol: changes in membrane permeability 5. Nephrotoxicity
*Which group does ketoconazole belong in? properties of the drug? any specific requirements?
Group: imidazoles. Properities: highly lipophilic, highly protein bound. Requirements: Needs LOW GI pH to be absorbed. (i see keto, i think ketoACIDosis, so i think need acidic PH to be absorbed. think that this requirement is because it's so lipophilic and protein bound)
*what group does clotrimazole belong in? Properties of the drug? metabolism?
Group: imidazoles. Properities: slightly water soluble. Metabolism: undergoes first pass effect. (the clot has been passed)
*what group do miconazole/enilconazole belong in? notable things about these?
imidazoles. have ether group, which gives low topical absorption (ETHER EN MY nose, not skin)
*what are the side effects of the imidazoles? (5)
(ketoconazole, clotrimazole, miconazole, enilconazole) GIT upsets, dec appetite, hepatotoxicity, inhibit CYP450, inhibit PgP= p glycoprotein....inhibit outward xport of pgp substrates (IM got a tummy ache-->well, GIT upset and a toxic liver would decrease your appatite, and liver issues affect CYP450...and CYP-->PgP/xport of PGP unhappy)
why are most imidazoles topically used?
they are highly lipophilic! so they will stay on the lipid layers of the skin
azoles-->triazoles. admin? spectrum?
Topical AND systemic use. BROAD spectrum. (TRI it all!)
*fluconazole is in which group? properties? excretion?
in triazoles.(more) water soluable, minimally protein bound, LARGE VD, penetrates barriers, renal excretion (the flu goes all over your body-- so it gets everywhere)
*itraconazole is in which group? properties? excretion?
in triazoles. highly lipophilic, active metabolite!!!, biliary excretion ( IT loves livers, so it is HIGHLY ACTIVE to get to bile needs to be fatty)
*voriconazole/posaconazole are in which group? properties? metabolism?
in triazoles. poor water solubility, hepatic metabolism
*what are the side effects of the triazoles?
teratogenic, hepatotoxic(itraconazole), inhibits CYP 3A(itraconazole) (in mammalian cells) (tri, terato, and ITRAS go through the liver and have active metabolites, so the other two make sense)
check out slide 19 table
summary of effects-- dont pay too much atten if its 1st or 2nd generation (he said)
what are the mechanisms of resistance against azoles? (4)
(1) fail to accumulate (inc out or dec in) (2) altered 14-demethylase (the CYP450 enzyme which converts lanosterol-->ergosterol) (3) diminished affinity for the CYP450 (changes in interactionof drug w target enzyme) (4) changes in other enzymes in the ergosterol path (compensating or circumventing the toxic consequences of changes in ergoesterol composition)
flucytosine is converted via a fungal enzyme(no animal analogue=selective tox) to an ANTI-metabolite of 5-fluorouracil (5-FU.) 5-FU interferes with thymidylate synthetase and thus DNA synthesis
*spectrum of flucytosine?
narrow (inhibiting fungal thymidylate synthetase and DNA synthesis-->selective toxicity bc not all fungi have this enzyme)
*super important thing you should know about flucytosine?
RAPID EMERGENCE OF RESISTANCE--DO NOT USE ALONE!!! (the flu likes company...)
side effects of flucytosine?
infrequent unwanted side effects
*spectrum of griseofulvin?
small spectrum (small grizzle is the only acceptable kind)
*what is griseofulvin effective against?
Trychophyton, Epidermophyton, Microsporum (MET would die if she ate grizzle)
*MOA of griseofulvin?
interferes with mitosis by binding to fungal microtubules
*indications of griseofulvin?
dermatophytosis!! involved with any of the fungi within its small spectrum (Trychophyton, Epidermophyton, Microsporum)
*pharmacokinetics of griseofulvin (properties, solubility, absorption, distributes where?)
oral absorptin varies with preparation and particle size. Distributes to the SKIN! (thus, good with dermatophytes) (i will only eat grizzle depending on its size. I'm looking at you, sausage)
*side effects of griseofulvin?
INDUCES CYP450. causes important drug interactions. also embryotoxic and teratogenic (grizzle getting lodged in your liver enzymes is bad for little fetuses)
MOA of echinocandins?
inhibition of 1,3-Beta-glucan synthesis--> disruption of fungal cell wall. The disruption of the wall mannoproteins which leads to exposure of antigen and greater immune system response
pharmacokinetics of echinocandins. (admin? good against what? not good against what? pertinance to vetmed?)
POOR oral bioavail. IV admin q24hrs. Effective against invasive forms of fungal infections (aspergillosis, candidiasis). NOT YET USED in vetmed (no efficacy against the yeast form of fungi) (the little echino will kill invaders in its nesting area)
*allylamine--> what is the drug in this category?
terbinafine (ally loves wear turbans)
* terbinafine. what is the MOA of terbinafine?
non-competitive inhibition of squalene epoxidase (which makes squalene-->lanosterol. remember that lanosterol then --> ergosterol, which is inhibited by azoles)
*allylamine--> terbinafine. pharmacokinetics? (properities, absorbed well where, goes where, metabolism and excretion? side effects?)
lipophilic (so big VD). rapidly absorbed from GIT, rapid diffusion to dermis and epidermis, limited side effects!! (ally loved fat turbans, shed eat them till her skin was covered in them!)
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