Antiparasitics 2 (LaCount) Flashcards
Parasitic infections associated with HIV (U.S. and Global)
US = PCP, Toxo, Crypto
Worldwide = Malaria, Leshmania, T. cruzii (Chagas)
Pentamidine mechanism
unknown
Pentamidine’s major problem
its highly toxic
50% of patients have sides
Pentamidine ROA
parenteral
Pentamidine Sides
hyper/hypoglycemia (rare)
Pentamidine is first line for what?
West African Trypanosomiasis
**also Alternative treatment for visceral leishmania and Pneumocystosis
Anaerobic protozoa
- E. Hystolytica
- Giardia
- Trichomonas vaginalis
One of the most common water borne illnesses in US
giardia
Incidence of T. vaginalis in US
20-25% of women
E. Hystolytica cysts are killed by…
boiling, but not by chlorination
Amebiasis is more common ________, but…
Latin america, Africa, India
but it can occur anywhere
Most amebiasises are _____
but…
asymptomatic
but some people develop liver abscesses
Giardia incidence in developed countries
2% adults
7% kids
Most common intestinal parasite in US
giardia
Giardia Tx
Metronidazole
Nitazoxanide
Cryptosporidium is the most frequent cause of…
recreational water-related disease outbreaks
Most common Cryptosporidium symptom
watery diarrhea
other sx = N/V, cramps, dehydration, weight loss and fever!
Drug of choice for Cryptosporidium
Nitazoxanide!
T. vaginalis Sx
vaginitis with purulent discharge
vulvar and cervical lesions
(often asymptomatic in men)
Metronidazole is DOC for
E. histolytica, Giardiasis, Trichomonas
Mzole kills…
kills trophozoites, not cysts
Mzole mechanism
unknown
activated by anaerobe ETC proteins
Drug similar to Mzole? How is it different?
Tinidazole
lower toxicity
Mzole and alcohol may result in…
Antabuse effect
= N/V, Tachycardia
Mzole blocks ACETALDEHYDE DEHYDROGENASE
amebiasis treatment - drugs for intestinal forms
Paromomycin + Iodoquinol
Paromomycin catergory
distribution
also effective against…
Aminoglycoside
not significantly absorbed in GI
also effective against Cryptosporidium
Iodoquinol is an alternative to ____
commonly used in combo with _____
Mechanism?
Alt to Paromomycin
Combo wiht Mzole
Mechanism unknown
Nitazoxanide PK
Mechanism
inhibits what organisms?
Rapid metabolism to tizoxanide
Interferes with PFOR (pyruvate ferredoxin oxidoreductase)-dependent electron transport reaction —> inhibits anaerobic metabolism
Inhibits: Sporozoites + Oocysts of Cryptosporidium parvum
Trophozoites of Giardia
95% of trypanosomiasis due to what?
brucei gambiense – west african trypanosomiasis
5% of trypanosomiasis caused by …
brucei rhodesiense – east african trypanosomiasis
Chagas disease caused by
trypanosoma cruzii
Trypanosome unique features
Unique organelles - kinetoplast, glycosome
Distinct mech’s of gene expression
Leshmaniasis drugs
Sodium Stibogluconate
Amphotericin B
Alternative meds for leshmaniasis
pentamidine or MILTEFOSINE
African trypanosomiasis drugs
Early stage
- Pentamidine (West)
- Suramin (East)
Late stage
- Melarsoprol (E/W)
- Eflornithine (West)
American trypanosomiasis drugs
Nifurtimox
Benznidazole
Miltefosine is a ____ analog
Approved for use against ______ in india
Phospholipid
Visceral leishmaniasis
Why would one avoid Miltefosine?
It is teratogenic
(avoid if pregnant)
Most commonly used drugs for T. cruzi
Nifurtimox and Benznidazole
Nifurtimox and Benznidazole mechanism
Activated by a NADH-dependent nitroreductase (mitochondrial)
= generation of nitro radical ions
Benznidazole is preferred to nifurtomix because…
it is less toxic
N + B reduce _______ of T. Cruzi
BUT they do not…
reduce the severity of the acute phase of T. Cruzi
…does not reverse the tissue damage caused by chronic infections
With N + B treatment, ____ is common. over the course of treatment, which is about ________ in duration
toxicity
3-4 months
Worms have a unique biology in that they… (2)
- multiply outside of their definitive host
- Evade the immune system (lifetime chronic infections)
Helminths include what catergories
Cestodes (tapeworms)
Trematodes (flukes)
Nematodes (Roundworms)
Echinococcosis
- aka
- forms what?
- treatment
Dog tapeworm
forms hydatid cysts in the liver
Albendazole and surgical excision of cysts
Cystercercosis
- caused by
- produces
- Tx
- caused by Taenia solium
- produces cysterci in the brain and eyes
- praziquantel, albendazole, surgery
Taeniasis
- caused by (aka)
- produces
- Dx and Tx
T. saginata (beef tapeworm)
does NOT produce cysterci
Dx by proglottids in stool, Tx: Niclosamide
Diphyllobothriasis
caused by/aka
Dx/Tx
Caused by D. latum (fish tapeworm)
Stool eggs, Tx = Niclosamide
Taenia solium causes what two syndromes
Taeniasis (intestinal infection, stool/niclosamide)
Cystercercosis (brain infection, prazi/albend)
Which form of Taenia saginata/solium penetrate the intestinal wall and circulate to musculature
Oncosphere
Cysticercosis 4 steps
- ingestion
- oncospheres hatch in intestine
- oncospheres invade intestinal wall and migrate to striated muscle, brain, liver
- develop into cysticerci
Pinworm disease
- organism
- hosts
- Dx and Tx
Enterobiasis
- Ent. vermicularis
- humans only host
- perianal egg ID, Mebendazole or Pyrantel pamoate
Roundworm disease
- Organism
- type of infection
- Dx
- treatment
Ascariasis
- Ascaris lumbricoides (most prevalent multicellular parasite)
- Intestinal growth of larvae
- stool egg ID
- Mebendazole or pyrantel pamoate
Threadworm disease
- organism
- disease/infection characteristics
- transmission
- Dx and Tx
Strongyloidiasis
- Strongyloides stercoralis
- Usually benign, can be fatal in ICP due to CNS/organ infctn (HYPERINFECTION SYND)
- Stool larvae, Tx = Thiabendazole, albendazole, ivermectin
Hookworm disease
- organism
- transmission
- Dx and Tx
- Ancylostoma duodenale and Necator americanus
- direct penetration of the skin
- eggs in stool, pyrantel pamoate or mebendazole
Whipworm disease
- Organism
- Sx
- Transmission
- Tx
- trichuris trichiura
- N/D, rectal prolapse
- ingestion of contaminated soil
- Mebendazole
River blindness
- organism
- features/Sx
- Transmission
- Dx
- Tx
- Onchocerciasis (volvulus)
- SubQ nodules, ocular lesions
- blackfly bite
- Detect microfiliariae in skin
- Ivermectin or surgery
Visceral larva migrans
- organism
- only ___ cause disease
- Dx
- Tx
Toxocara canis
only larvae cause disease
ID larvae in tissue
Mebendazole / thiabendazole
Filariasis
- organism
- Sx
- Transmission
- Dx/Tx
- Wuchereria bancrofti
- elephantiasis
- Anopheles or Culex mosquitoes
- ID microfilariae in blood, Combo of DIETHYLCARBAMAZINE and ALBENDAZOLE
Disease from loa loa
Loiasis
Larvae under skin, leave track marks
worms visible in subconjunctival space
Treated with diethylcarbamazine
Dracunculiasis caused by…
drinking water containing intermediate host copepods where larvae live
…have to actually remove the subQ worms via surgery
Trichinella spiralis diagnosis
muscle biopsy that shows coiled encysted larvae
Benzimidazole drugs (3, one fact each)
Mebendazole (1st)
Thiabendazole (Toxicity limits use)
Albendazole (for GI and Tissue)
Bendimidazole MOA
binds to tubulin ->> inhibits formation of MT at the PLUS end (minus end still shortens)
Doesn’t bind to mammalian tubulin
Albendazole DOC for
Cysticercosis
Albendazole rapidly converted to ______
albendazole sulfoxide
(active metabolite)
Mebendazole used for..
pinworm, hookwarm, ascariasis, thricuriasis
Thiabendazole is not preferred b/c…
toxicity and potential teratogen
Praziquantel is effective against what catergories of organisms
cestodes and trematodes
NO effect on nematodes
Praziquantel MOA (lower concentrations)
increased muscular activity at lower [C]
Worms detach from blood vessel walls
migrate from mesenteric vv. -> liver
Praziquantel higher concentration MOA
tegumental damage
exposes a number of tegumentsl antigens
**may also disrupt CALCIUM homeostasis**
Prazi is the DOC for..
Dosing?
all forms of schistosomiasis
high cure rate with 2-3 doses
–> single dose kills 100% of T. saginata/solium, and D. latum
Toxicity for prazi:
more severe reaction to dying worms
Ivermectin is DOC for
strongyloidiasis and onchocerciasis
Ivermectin drug type
semisynthetic macrocyclic lactone
Ivermectin MOA
Paralyzes microfilariae
Binds to Glutamate-activated Chloride channels in nematode nerve/muscle cells
causes hyperpolarization by increaseing internal [Cl-]
*also binds to GABA-gated and ligand gated chloride channels
ivermectin doesnt kill…
adult worms
(only paralyzes)
Ivermectin used to treat _____
onchocerciasis
also for ascaris, enteroboius, strongyloides, filariasis
Treatment with ivermectin must be continued…
for the lifespan fo the adult worm
Pyrantel pamoate is a…
MOA?
What does it treat? (and dosing?)
…broad spec antihelminth (OTC)
MOA = Causes Ach release and inhibits cholinesterase
Tx for pinworms (moderate against hookworms)
- Ascariasis = one dose
- Pinworms = 2 doses 2 weeks apart
Scabies organism
sarcoptes scabiei
scabies burrow in what tissue
stratum corneum of the skin
causes itching and rash
Treatment for scabies
Permethrin cream
(salycylic acid if crusted scabies)
Head live tx
Permethrin or pyrethrin
1st application 10 minutes, second application 10 days later
Malathion if chronic
Newer pediculicides contain benzyl alcohol, dimethicone, or spinosad
