Fitz - Antifungal Drugs Flashcards
MOA: Amphoterecin B
insert into yeast membrane, physical association w/ ergosterol to form hydrophilic pores in cell membrane > disruption of membrane integrity
AEs: Amphotericin B Deoxycholate
-at infusion: chills, fever, anemia, hypotension
-later onset: nephrotoxicity
(mostly ass’d with the deoxycholate)
polyene drug
amphotericin B
mechanism of nephrotoxicity caused by amphotercin B
- direct damage to distal tubule
- Na, Mg, K wasting > hypokalemia
- decreased GFR> arteriole constriction
- further concentration of drug in tubule > inc damage
pts at increased risk for nephrotoxicity caused by amphotericin B
- transplant pt
- HIV pts
- pts with serious inf (gm(-), MRSA)
triazole drugs - 1st gen
- fluconazole
- utraconazole
triazole drugs - 2nd gen
- voriconazole
- posaconazole
MOA: fluconazole
- inhibition of lanoserol > ergosterol synthesis
- disrupts sterol content in cell membrane
what yeast CYP450 enzyme does fluconazole target?
14-alpha-demethylase
Fluconazole indications
- candida albicans
- cyptococcus (w/ AmpB)
Fluconazole limitations
aspergillus
Fluconazole clearance
75% renal
-good for candiduria
Itraconizole indications
- candida albicans
- other candida
- histo*
- coccidioides*
- blastomycoses*
voriconisol indications
- candida albicans
- other candida
- aspergillus
echinocandins
- caspifungin
- micafungin
- anidulafungin
MOA: echinocandins
inhibition of beta-(1,3)-glucan synthase leading to osmotic fragility of the fungal cell wall
metabolism of caspofungin
hepatic - good for renal pts
what type of pts do you worry about caspofungin drug interactions with?
immunocomp pts d/t cyclocporine or tacrolimus
caspofungin indications
-serious opportunistic infections (candidiasis, aspergillosis)
how long can it take to see results of antifungals?
up to 8 days!
what would you use in an HIV pt with cadidiasis who failed fluconazole, amphotericin B, and itraconazole
caspofungin
caspofungin limitations
- histoplasmosis
- coccidiomycosis
- fusarium spp
histoplasmosis has been ass’d with what type of therapy?
anti-TNFalpha therapy
most common pulmonary and systemic mycosis in humans
histoplasmosis
triazole opportunistic indications
- aspergilllus
- candida
- rhizopus
- cryptococcus
triazole pathogenic indications
- histoplasma
- coccidioides
- blastomyces
- paracoccidiodies
intraconizole is front line tx for
- histoplasmosis
- coccidioides
- blastomycoses
tx of oral candidiasis in HIV pts
- oral fluconazole
- can also use itraconazole
drug of choice for invasive aspergillosis
voriconazole
what do you use for candidiasis resistant to fluconasole (C. krusi, c. galbrata)
voriconazole
AEs: ketoconazole
- inhibition of adrenal and gonadal steroid synthesis
- gynecomastia
- decreased libido
2 triazoles with wide dist including the CSF
- voriconazole
- fluconazole
what would impair the absorption of itraconazole?
antacids - needs gastric acidity to dissolve
2 triazoles that inhibit hepatic CYP450 and enhance renal toxicity
- voriconazole
- itraconazole
why do you avoid voriconazole in kids?
vision disturbances
rare fungal infection ass’d with tornado-related wounds
zygomycosis
tx of mucormycosis (zygomycosis)
amphotericin B
drug of choic for crytoccal meningitis
amphotericin B + 5-FC
MOA: 5-FC
inhibition of DNA & protein synthesis
intrinsic resistance to 5-FC is caused by
mutated cytosine permease (can’t cross cell membrane)
acquired resistance to 5-FC is caused by
mutated cytosine deaminase (can’t be converted to active form, 5-FU)
role of amphotericin B in tx of cryptococcal meningitis
creates ergosterol pores for 5-FU to enter in the case of resistance
