Why even in an asymptomatic individual is it important to treat entamoeba histolytica?
B/c they can pass it on to the elderly or those who are immunocompromised
How do we treat people with
asymptomatic
entamoeba histolytica?
With
acute intestinal or hepatic
entamoeba histolytica?
asymp: iodoquinol and paromomycin
symp: metronidazole and tinidaozole (metro)
A person who recently went camping and ran out of bottle water their last day presents with GI distress, cramping, and gas.
What are they infected with? What do we treat them with 1st line? (3)
- giardia lamblia from stream water
- 1st: metronidazole, tinidazole, and nitazoxamide
What are 2 alternatives for Giardia lamblia?
- albendazole/mebendazole
- paromomycin (if preg)
What is leading cause of watery diarrhea in the USA?
cryptosporidium parvum
What do we use to treat cryptosporidium parvum?
Nitazoxanide
(knit sox)
This commonly causes travelers diarrhea from drinking contaminated water and eating contaminated produce
Cyclospora cayetanensis
How do we treat Cyclospora cayetanensis?
Sulfamethoxazole/trimethoprim
(sulfacayte)
This can cause a vaginal infection. What do we treat it with?
Trichomonoas vaginalis
metronidazole
This often presents in children with perineal itching. What do we treat it with (3) and importantly who must be treated with it?
- pinworm: albend, mebend, pyartenl pamoate
- treat the whole family if we see a child with it bcc readily spreads
What do we treat the large roundworm Ascaris lumbricoides with? (2)
- albendazole
- mebendazole
What are the two hookworms?
What do we treat them with? (2)
- necator americanus
- ancyclostoma duodenale + braziliense
- albendazole and mebendazole
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How do most people get infected with a hookworm?
Walking without shoes and then having the hookworm invade through the skin (invades through skin but then moves through to intestinal tract)
(red boots)
Where do we see most hookworm infections in the USA?
Southern USA
Strongyloides stercoralis or the threadworm is a helminth. What do we use to treat it? (2) How does it infect?
- ivermectin and albendazole
- can infect through the skin and then moves to lungs and back down to intestinal tract (arrow on shirt)
Teichuris trichura is a helminth called the whipworm what do we treat it with?
mebedanzole
(try and trick me, i'll bend over)
All tapeworms (cestodes) except for one are treated with what?
praziquantel
What is the one tapeworm (Cestodes) that is not treated with praziquantel?
T. solium > neurocysticercosis can be treated with:
- albendazole, praziquantel, anticonvulsants (stops seizures), and glucocorticoids (stops the inflammation of dead cysts)
Praziquantel is almost exclusively eliminated by CYP _ which normally will be induced by the anticonvulsant drugs if someone has seizures or has neurocysitercercosis
3A4
Why do combine albendazole and praziquantel? (2)
- they are synergistic in killing the worms and cysts
- prazi has cyp interactions so we give albend alongside
Both fasciolopsis buski and clonorchis sinensis are trematodes (flukes) that are treated with what?
praziquantel
what are the 2 classes of anti-protozoal drugs?
- luminal agents that poorly absorbed and stay in GI lumen
- drugs that treat tissues forms
What are the 2 luminal agents? 2 Tissue agents?
luminal: Iodoquinol + Paramomycin
tissue: Nitazoxanide , 5-Nitroimidazoles (metro + tinidazole)
This drug is indicated in the treatment of entamoeba histolytica (and other amoebas) in minor cases and then in severe after another drug.
Iodoquinol
(iodo queen)
In a severe case of an amoeba infection what 2 drugs do we give?
A course of metronidazole and then Iodoquinol
(metro, iodo queen)
How long is the Iodoquinol treatment?
long (why paromomycin = preferred)
Iodoquinols MOA is unknown but what does it kill?
Kills luminal parasites in both the
trophozoite and encysted forms
What are the ADRs for Iodoquinol? (3)
- GI disturbances: D/N/V pain
- contains iodine: can disrupt thyroid function (hypo or hyper)
- can cause Iodine toxicity (dermatitis and urticaria, itchiness, fever)
Who is iodoquinol CIed in? (2)
- those with iodine intolerance
- pre existing liver disease
A very rare ADR for iodoquinol is what?
optic neuritis or optic atrophy
(EYE-odoquinol)
This drug is indicated as the drug of choice for entamoeba histolytic and other amoebas in the USA
Paramomycin
(pair of mice)
Why is paramomycin the drug of choice in the usa for amoebas? (2)
- kills luminal parasites
- fewer side effects and shorter course than iodoquinol (preferred)
What else is paramomycin indicated in?
Giardia lamblia especially in pregnant women (luminal so not absorbed)
Paramomycin MOA?
binds to 30S ribosomal subunit of protozoa
Even though paramomycin will kill trichomonas by binding to its 30S ribosomal subunit why is it not used?
b/c it gets trapped in the GI lumen and won't be able to get to the vagina
What are the ADRs for Paramomycin? (4)
- GI disturbances
- disruption of the gut micro biome that may cause C. diff
- ototoxicity
- renal toxicity
When will ototoxicity and renal toxicity possibly occur in someone taking paramomycin?
If the GI epithelium becomes compromised and the drug is able to move systemically
This drug is used to treat cryptosporidium parvum and Giardia Lamblia for a short 3 day course
Nitazoxanide
What is Nitazoxanide MOA?
Interferes with the pyruvate ferredoxin oxidoreductase (PFOR) enzyme-dependent electron transfer reaction involved in anaerobic energy metabolism
(knit sox FOR someone)
What is the active metabolite of nitazoxanide?
Tizoxanide
nitazoxanide will inhibit growth of crypto _ and _ and giardia _
sporozoites and oocysts
trophozoites
What are the ADRs for nitazoxanide? (2)
- yellow-green discoloration of the urine
- yellow discoloration of the eye
These two drugs are used together in large doses to treat Giardia and trichomonas vaginalis
Metronidazole and tinidazole
What parasite do we give metronidazole and tinidazole in larger quantities to treat?
entamoeba histolytica
What are metronidazole and tinidazole's MOA?
- bactericidal activity
- prodrugs that move inside cells and accept e- from reduced ferredoxin to produce highly reactive nitro radical anions which disrupt DNA
When we say metronidazole and tinidazole can be recycled what do we mean? What is a problem with this?
- they can lose the electron they accept but then just become their parent drug again and can accept another to keep working
- in the human body O2 can compete and decrease activation of the drug and increase recycling
What parasites are readily resistant to metronidazole and tinidazole? How? (2)
- T. vaginalis + G. lamblia
- O2 scavenging by the normally anaerobic parasite that causes it to have too much O2 and thus outcompete the drugs
- decreased levels of PFOR and ferredoxin can decrease the donation of the electrons
What are the ADRs for Metro and T? (3)
- GI problems
- metallic taste in mouth (metal metro)
- rare: seizures and peripheral neuropathy
What are the drug to drug interactions of metronidazole and tinidazole? (2)
- disulfiram like effects (V, headache, flushing)
- CYP3A4 interactions
When are M&T CIed? (5)
- pregnancy
- lactation
- Caution with alcoholism
- Caution with kidney AND liver disease
Pyrantel pamoate is indicated for these 2 organisms:
- enterobius vermicularis
- ascaris lumbricoides
Pyrantel pamoate similar to paramomycin is used in _
pregnancy
What is PP MOA?
- it's a depolarizing neuromuscular blocker that stimulates the release of ACh and blocks cholinesterase
= worm muscles contract and the worm to release hold on intestinal wall and be expelled
What are the ADRs for PP?
GI upset
What can we use Albendazole and Mebendazole to treat? (4)
- Necator and Ancyclostoma (hookworms)
- enterobius vemricularis (pinworms)
- ascaris lumbricoides (large worm)
- giardia alternative
What is better treated with just mebendazole?
tirchuris trichura
(try and trick me, i'll bend over)
What is better treated with just albendeazole? (2)
- tapeworms (neurocysticercosis)
- strongyloides stercoralis
We can use Ivermectin to treat what?
strongyloides stercoarlis
We can use praziquental to treat what? (4)
- cestodes: diphyllobaothrium datum (fish tapeworm) > have to give Vb12 too
- cestodes: Taenia solium
- trematodes: Fasciolopsis buski + clonorchis sinensis
Drug to treat a pt. w/ bloody diarrhea, RUQ pain, elevated liver enzymes and cysts with cigar bodies on O&P
metro
nidazole or tinidazole
(acute
Entamoeba histolytica
infection)
Tx for a pt. w/ diarrhea and abdominal pain who recently bathed in a river in SE Asia with pigs nearby
Praziquantel
Only parasite we talked about using iodoquinol for, and when would you used it?
Entamoeba histolytica
- given after a course of metronidazole for symptomatic individuals
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..
Signs of iodine toxicity: (4)
dermatitis, urticaria, pruritus, fever
What "secondary infection" may occur as a result of paramomycin?
C. difficile due to disruption of gut microbiome by an abx
2 parasites treated with nitazoxanide
- cryptosporidium parvum
- giardia lamblia
3 parasites treated with 5-Nitroimidazoles
- giardia
- trichomonas vaginalis
- entamoeba histolytica
Effect of oxygen on metronidazole?
decreases activation by competing for electrons (increases recycling)
Diarrhea is commonly associated with which antiparasite drugs (3)
- paramomycin
- iodoquinol
- pyrantel pamoate
Which of these drugs has the lowest incidence of GI side effects?
Nitroxanide
Which of these drugs is likely to cause constipation? (2)
Metronidazole, Tinidazole
What side effect can all of these drugs cause?
Nausea and vomiting