Anti-fungal Drugs Flashcards by Taryn W

Which fungi cause superficial mycoses (dandruff, tinea vesicolor)

malessezia globosa, malessezia furfur

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what fungi cause cutaneous mycoses? (dermathphytosis)

microsporum, trichophyton, epidermophyton

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what is a cutaneous mycosis called that isn’t caused by microsporum, trichophyton, or epidermophyton?

dermatomycosis

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microsporum, tricophyton, and epidermophyton infect what to cause dermathphytosis

infect skin, hair, nails

metabolize and live off of keratin

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cutaneous mycoses are often associated with areas of the body that are:

poorly aerated
excessive moisture/sweatuing
tight clothing
high humidity

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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)

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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

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what are some examples of subcutaneous mycoses?

sporotrichosis (rose handlers disease)
chromoblastomycosis
mycetona

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what fungi causes sporotrichosis

sporothrix schenckii

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what fungi causes chromoblastomycosis

many agents, all dematiacious fungi

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systemic infections can be either:

dimorphic

opportunistic

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what are some examples of infections that are considered systemic?

soft tissue
UTI
pneumonia
meningitis
septicemia (in blood)

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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

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what are the different systemic mycoses that can occur

histoplasmosis
blastomycosis
coccidiomycosis
paracoccidiomycosis

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blastomyces dermatitidis is endemic to:

mississippi river, ohio river, great lakes

characterized by broad based budding with thick walls that appears double contoured

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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

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paracoccidiodes brasiliensis is endemic to:

central and south america

90% of symptomatic disease found in males
mariners wheel morphology

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histoplasma capsulatum is endemic to:

eastern and central USA

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the opportunistic mycoses are:

candidiasis
cryptococcosis
aspergillosis
mucomycosis
pneumocystis jiroveci

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what populations have the tendency to be immmunocompromised?

debilitated patients
indwelling catheters
prosthesis
HIV 
diabetes or chronic renal, hepatic, cardiac disease
alcoholism

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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

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describe mucosal candidiasis

thrush

can be oral, vulvovaginal, esophogeal

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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***

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describe aspergillosis

caused by aspergillus, several species
found in dust, soil, decomising organic matter (environmental)
- spores inhaled and can have a variety of symptoms

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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