lec 7 antifungals, anti-protozoans, and antiparasitics

two main species of fungi

unicellular yeasts

filamentous molds

what is the ocular involvement of fungi

there is an enhanced risk of infection with contact lens wear, steroids, trauma, and immunocompromised people 

what are the antifungal classes

polyenes

pyrimidines

azoles

echinocandins

what is the only FDA approved med for antifungal

natamycin (mold)

polyenes

amphotericin B

natamycin

mystatin

pyrimdines

flucytosine

azoles

ketoconazole

fluconazole

posaconazole

voriconazole

itraconazole

miconazole

echinocandins

caspofungin

micafungin

anidulafungin

what is the better option for yeast

amphotericin B 

what is nystatin used for

yeast & mold

what are polyenes similar to

cell membrane antibiotics

they bind to fungal ergosterol (increase membrane permeability)

very little resistance

what are pyrimidines similar to

DNA synthesis antibiotics

they inhibit thymidine synthesis

they develop resistance; rarely used alone 

what are azoles similar to

folic acid or protein synthesis inhibitors

they impair ergosterol synthesis and some cytochrome P450 enzymes; may reduce metabolism of other drugs

they develop resistance

what are echinocandins similar to

cell wall antibiotic inhibitors

they inhibit glucan syntehsis - weaken cell wall

poor oral availability

what is ergosterol a precursor of

vitamin D

needed to form the cellular membrane

what is amphotericin B’s adverse reactions

renal toxicity

when thinking of antifungal adverse reactions, what is the first one you should think of

hepatotoxicity EXCEPT FOR amphotericin B (renal toxicity)

what is a protozoal infections

acanthamoeba

acanthamoeba

most common protozoa found in soils and water(fresh water, lakes, etc)

infection of the eye can cause sight threatening keratitis

it can carry several other bacteria and causes replication & infections such as: 

• e coli

• staph aureus 

• pseudomonas 

• legionella pneumophilia

this is responsible for the most virulent form of infectious keratitis with the worst prognosis

how do you get acanthamoeba

most cases are bc of contact lens wear > trauma

what is the life cycle of acanthamoeba

trophoxites ←→ double walled cysts

• when they become double walled cysts that makes them very resistant to killing

they’re found in fresh water, soils, and airborne cysts

what will you see with acanthoemba

the white stromal ring (similar to what it looks like with anesthetic abuse)

BUT ANESTHETIC ABUSE = NO PAIN

ACANTHOAMEBA = SEVERE PAIN

• bc it tends to attack the corneal nerve endings

how is the management of acanthamoeba

med therapy not well established but if you tx early you can be fine but most of em end up in a corneal transplant ☹

tx of acanthamoeba

1. corneal epithelial debridement

2. topical biguanides every hour-every 3 hours for 3-4 weeks to months

   1. polyhexamethylene biguanide + prpamidine

   2. bisbiguanide + propamidine

^ these are specific to acanthoemba not an antibiotic

what is an even better tx for acanthamoeba than the biguanides

akantior (polihexanide 0.08%)

toxoplamosis

lives in soil

• poorly cooked food

• unwashed veggies

• exposure to cat poop

you can infected but be asymptomatic while carrying the disease 

• if ur immunocompromised that can cause retinal infections 

where will you find toxo in the eye

posterior pole near the macula

acute phase toxo tx

sulfadiazine + pyrimethamine

sulfamethoxazole + trimethoprim

clindamycin

spiramycin

latent phase toxo tx

atovaquone

clindamycin

what is clindamycin good for

toxo & anaerobic bacteria

what kind of disease is toxo

obligate intracellular parasite

• needs host machinery to survive

what does demodex have

collarettes at the base of the lashes

cylindrical debri filled with keratin

what are demodex

mites that are obligate 

they live in our lashes

types of demodex & class

demodex folliculorum → longer, in the hair follicle

demodex brevis → shorter, in the sebaceous gland)

class: arachnida

does demodex increase or decrease with age

increases

what is the only FDA approved med for demodex & dosage 

xdemvy

a lotilaner 0.25% anti-parasitic solution

BID x 6 weeks

it is a gamma-aminobutyric acid (gaba) gated chloride channel inhibitor selective for mites

what are the sleeves we see in demodex made out of

keratin

epithelial cells

eggs

waste

“demodex poop”

why is the dosage for xdemvy 6 weeks?

bc the lifespan of the mites is 2-3 weeks so you wanna do it longer to make sure that the mite has acc went away

when acetylcholine binds to the nicotinic receptor what happens

you get an action potential aka muscle contraction 

what happens with GABA and xdemvy like how does that whole process work

GABA normally binds to the gaba gated chloride channel allowing chloride to get in which stops the action potential allowing ur muscles to relax (not contract)

xdemvy INHIBITS the gaba gated chloride channel

“xdemvy paralyzes the demodex mites” so it doesnt allow them to relax, it leaves them in their contracted form so they cant move or feed - they go bye bye

what are the adverse events of xdemvy

stings & burns (like all other drops) 

<2% chance of developing chalazion/hordeolum, punctate keratitis while on the medication (prob bc of the bacteria that the mite carries)

potassium sorbate perservative can discolor contacts so make sure to tell pt to remove them for 15 min 

• this is for soft contact lenses

• it doesnt do anything to RGPs or sclerals

what are the precautions for preggo for xdemvy & is it safe for children?

preggo cat B

not established for kids bc not a lotta people are exposed to demodex