Anti-fungal Drugs Flashcards
Which fungi cause superficial mycoses (dandruff, tinea vesicolor)
malessezia globosa, malessezia furfur
what fungi cause cutaneous mycoses? (dermathphytosis)
microsporum, trichophyton, epidermophyton
what is a cutaneous mycosis called that isn’t caused by microsporum, trichophyton, or epidermophyton?
dermatomycosis
microsporum, tricophyton, and epidermophyton infect what to cause dermathphytosis
infect skin, hair, nails
metabolize and live off of keratin
cutaneous mycoses are often associated with areas of the body that are:
poorly aerated
excessive moisture/sweatuing
tight clothing
high humidity
what are some examples of cutaneous mycoses
skin mycoses aka ringworm tinea corporis tinea pedis (athletes foot) tinea cruris (jock itch) tinea capitis (mycosis of scalp) tinea barbae (mycosis of beard) tinea unguium (mycosis of nail, aka onychomycosis)
what are the characteristics of subcutaneous mycoses?
chronic, localized
following traumatic implatation with soil fungi
may appear as a small nodule that grows and may drain or ulcerate
can become systemic, especially in immunocompromised
what are some examples of subcutaneous mycoses?
sporotrichosis (rose handlers disease)
chromoblastomycosis
mycetona
what fungi causes sporotrichosis
sporothrix schenckii
what fungi causes chromoblastomycosis
many agents, all dematiacious fungi
systemic infections can be either:
dimorphic
opportunistic
what are some examples of infections that are considered systemic?
soft tissue UTI pneumonia meningitis septicemia (in blood)
what are the characteristics of systemic mycoses?
entry into host by inhalation of airborne spores
spores germinate in lung
asymptomatic primary pulmonary infection is common
acute pulmonary disease less common
chronic pulmonary or dissemination infection is rare
-can infect immunocompetent or immunocompromised patients
-fungus endemic to a particular region
what are the different systemic mycoses that can occur
histoplasmosis
blastomycosis
coccidiomycosis
paracoccidiomycosis
blastomyces dermatitidis is endemic to:
mississippi river, ohio river, great lakes
characterized by broad based budding with thick walls that appears double contoured
coccidioides immitis is endemic to:
southwest USA
valley fever
appears with arthrospores when grown in lab
-dont want to expose lab workers so often sent away for molecular testing
paracoccidiodes brasiliensis is endemic to:
central and south america
90% of symptomatic disease found in males
mariners wheel morphology
histoplasma capsulatum is endemic to:
eastern and central USA
the opportunistic mycoses are:
candidiasis cryptococcosis aspergillosis mucomycosis pneumocystis jiroveci
what populations have the tendency to be immmunocompromised?
debilitated patients indwelling catheters prosthesis HIV diabetes or chronic renal, hepatic, cardiac disease alcoholism
describe candidiasis
candida albicans - most common species
overgrowth –> yeast infection
-normally kept under control by normal bacterial flora (almost all infections are endogenous)
lab ID by culture - gram positive, yeast with “feet”
usually occurs in moist areas
-can involve GI tract, kidnesy, liver, spleen, bloodstream, UT, respiratory tract, heart, eye
describe mucosal candidiasis
thrush
can be oral, vulvovaginal, esophogeal
describe cryptococcus
cryptococcus neoformans
site of infection = lung, meninges, CSF, blood, skin, mucous membranes, systemic
capsules stain pik with mucicarmine
diagnosis with india ink or antigen test* capsule***
describe aspergillosis
caused by aspergillus, several species
found in dust, soil, decomising organic matter (environmental)
- spores inhaled and can have a variety of symptoms
what does aspergillosis look like in tissue?
septated hypae
branching occurs at 45 degree angles
appears in radial facial, hypae nearly parallel
in cavitary lesions, conidial heads may be observed
describe mucomycosis
infection with zygomycete, rhizopus most comon
infection begins in nasal mucosa or sinuses and progresses to the orbit, palate, and brain
-aggressive and rapidly fatal
what do zygomycetes look like in tussue
large, nonseptated hypae
ribbon like
branch at 90 degrees
Name the antifungal drugs
ampotericin B, nystatin 5-fluorocytosine ketoconazole, miconazole, clotrimazole fluconazonle, itraconazole, voriconazole, posaconazole caspofungin, micafungin, anidulafungin griesofulvin terbinafine, butenafine, naftifine cicliprox, tolnaftate, selenium sulfide
what are the seven antifungal drug classes
polyenes azoles (imidazoles, triazoles) allylamines echinocandidins grisans pyrimadine miscellaneous
what is the target for polyenes?
ergosterol
what is the target for azoles and allylamines
ergosterol biosynthesis
what is the target for echinocandidins
cell wall biosynthesis (beta-1,3-glucan synthesis)
what is the target for griesans
microtubules
what is the target of pyrimidine analogs
DNA synthesis
permease critical
amphotericin B and nystatin are:
polyenes
5FC is:
pyrimidine analog
ketoconazole, micronazole, clotrimazole are:
imidazoles
fluconazole, itraconazole, voriconazole, posaconazole are:
triazoles
caspofungin, micafungin, anidulafungin are:
echinocandidins
griesofulvin is:
griesan
terbinafine, butenafine, naftifine are:
allylamines
cicliprox, tolnaftate, and selenium sulfide are:
miscellaneous antifungals
what are the uses for ampho B
drug of choice for must systemic life threatening fungal infections
very broad spectrum
usually given IV
no CNS penetration
what are the uses for nystatin
candida, especially thrush (cutaneous mycoses
minimal GI absorption so when taken orally, it only treats GI problems
what are the uses for 5FC
used in combination with ampho B to treat candida, cryptococcus, aspergillus (opportunisitic infections)
what are the uses for imidazoles
- ketoconazole, micronazole, clotrimazole
broad spectrum against fungi no CNS penetration oral and topical absorption requires an acidic gastric environment (decreased with antacids) mostly replaced by the triazoles
what are the uses for triazoles
-fluconazole, itraconazole, voriconazole, posaconazole
broad spectrum against fungi
better Gi tolerance
inhibits P450
all but itraconazole penetrate the CNS
which triazole cannot penetrate CNS
itraconazole
what are the uses over echinocandins
-caspofungin, micafungin, anidulafungin
used as a second line after ampho B
newer, expensive
effective against aspergillus, candida
what are grisans (griesofulvin) used for
tinea infections
effective against dermatophytes (fungi that metabolize keratin)
what are allylamines used for
terbinafine
butenafine
naftifine
treat tinea
topical application
-terbinafine is oral
what antifungals have mechanisms that are not well characterized?
cicliprox
tolnaftate
selenium sulfate
what is the mechanism of polyenes
amphotericin B
nystatin
forms pores in the membrane by binding to ergosterol causing loss of K and other small molecules
what is the mechanism of 5FC
enters fungus using permease (not found in mammals)
converted to 5FU and then incorporated into nucleic acid (pyrimidine analog)
what is the mechanism of imidazoles
ketoconazole, microconazole, clotrimazole
inhibits production of ergosterol from lanosterol
what is the mechanism of triazoles?
fluconazole, itraconazole, voriconazole, posaconazole
inhibits production of ergosterol from lanosterol
what is the mechanism of echinocandins
caspofungin, micafungin, anidulafungin
inhibits cell wall biosynthesis by inhibiting beta-gucan production
what is the mechainsm of griesofulvin
inhibits microtubule function, preventing mitosis
binds to keratin in skin and hair making them more resistant to fungal infection
what is the mechanism of allylamines
terbinafine, butenafine, naftifine
inhibits ergosterol production via squalene epoxide
what are the side effects of amphoB
nephrotoxicity
can make pores in human cells because it also can bind cholesterol to a certain extent
what are the side effects of nystatin
makes pores in human cells by binding to cholesterol
highly insoluble, toxic if given IV - topical and oral but minimal GI absorption)
what are the side effects of 5FC
bone marrow suppression
GI upset
what are the side effects of ketoconazole
inhibits with CYP450, interferes with testosterone and cortisol production
GI upset
hepatic dysfunction
what are the side effects of micronazole and clotrimazole
too toxic to give IV but also poorly absorbed as a topical
what are the side effect of the triazoles
CYP450 interactions
hepatic dysfunctions
-safer than imidazoles
which antifungals have few untoward effects?
echinocandidins
allylamines (headaches and gi upset minor)
driesofulvin has rare but serious adverse effects
what rare side effects does griesofulvin have?
hepatotoxicity, GI irritation
bone marrow suppression
headaches
