Fitzpatrick: Parasitic, protozoa, C diff Pharm Flashcards
What drugs are used for nematodes?
Albendazole Mebendazole Pyrantel pamoate Diethylcarbamazine Ivermectin
What drugs are used for Cestodes (tapeworms)?
Albendazole
Mebendazole
Praziquantel
Niclosamide
What drugs are used for Trematodes?
Praziquantel
What are the soil-transmitted helminths?
Ascaris
hookworm
trichuris
What is used to treat these nematodes in endemic areas?
Albendazole
- Mebendazole is older
- these are both benzimidazoles
MOA of benzimidazoles (Albendazole and mebendazole and Thiabendazole)
- they disrupt microtubule dynamics
- bind to parasite B-tubulin, disrupt microtubule polymerization and microtubule-dependent processes
- remember that microtubules are made from alpha and beta tubulin dimers…
Where are nematodes usually residing?
the intestinal tract
Why is mebendazole so great?
poor absorption, plus efficient metabolism, plus protein binding= LOW SYSTEMIC EXPOSURE
-so, it’s safe and effective :)
How is Albendazole bioavailability and distribution?
modest absorption+EFFICIENT METABOLISM = low systemic exposure to parent drug
-safe and effects as a single dose
Does albendazole itself have a lot of systemic exposure?
no, negligible
What does abendazole get metabolized to that gets distributed a lot more places to kill tissue dwelling helminths, hydatid cysts?
Albendazole to Albendazole sulfoxide
What does albendazole sulfoxide get metabolized to and what happens to it?
Albendazole sulfone
- inactive metabolite
- renal clearance
Why is Thiabendazole only good for cutaneous use?
it has high systemic toxicity
-it’s good for larval migrans apparently
Which anti-helminthic drug should be used for Enterobius vermicularis (pinworm)?
Mebendazole
Which anti-helminthic drug should be used for Ancylostoma duodenale (Hookworm)?
Albendazole
Ascaris lubricpoides?
Albendazole and Mebendazole
Trichuris trichiura (whipworm)?
- Mebendazole
- Albendazole
- 3 day course most effective
Toxocara spp
Larval migrans
Albendazole
Why are we scared of albendazole and mebendazole in preggo people?
They are embryotoxic and teratogenic in preggo rats
-Pregnancy category C, not recommended in humans
What is an alternative or adjunctive nematode therapy that is effective against hookworm, pinworm, and roundworm but INEFFECTIVE AGAINST TRICHURIS TRICHIURA?
Pyrantel pamoate
What is in the NM junction of nematodes
N-AChR
-so they use acetylcholine a lot
What is Pyrantel
a depolarizing NM blocking agent
-causes persistent activation of nicotinic acetylcholine receptors (N-AChR) and spastic paralysis of the worm
What should we consider when we give pyrantel?
Worm burden
-they can get into places we don’t want them to be and clog up the joint
What is the active ingredient in Pyrantel Pamoate?
- Pyrantel
- Pamoate is just the chewable component
Pyrantel’s bioavailability
Poorly absorbed from the GI tract
- confines its action to intralumenal GI nematodes
- less than 15% excreted in urine as parent drug and metabolite
What ppl do we use Pyrantel with caution?
Pregnant women and children <2
What was the other NEmatode/Helminth therapy we talked about?
Ivermectin
What is Ivermectin used for?
intestinal strongloidyiasis- thread worm
and
Onchocerciasis- River Blindness
What does Ivermectin do?
Activates Glutamate-Gated Chloride Channels
- causes Cl-current
- hyperpolarization
- paralysis
Can Ivermectin cross the BBB?
no
-so it won’t mess with our GABA gated CL channels
So, when is Ivermectin usually contraindicated?
When the Blood brain barrier is disrupted (meningitis, Trypanosomiasis)
What has been the most extensive use for ivermectin in humans?
Onchoceriasis (River blindness) control in Africa
- also useful for lymphatic Filariasis
- Wuchereria bancrofti
- Brugia malayi
What is Diethylcarbamazine used for?
- Lymphatic filariasis
- Loasis
What is bad about Diethylcarbamazine?
significant toxicity due to host-response following death of parasites
What are the Cestodes that we have to worry about?
Cysticercosis
Echinococcosis
Taeniasis
Diphyllobrothriasis
When are people in an infective stage with Cysticercosis?
When they have EGGS in their stool
When are people in the Diagnostic stage of cysticercosis?
When there are gravid proglottids in the feces
What is the drug of choice for all adult form tapeworm infection?
Praziquantel
What drug is used elsewhere but not in the US for tapeworm infections?
Niclosamide
What is the drug of choice for LARVAL forms of tapeworm infections?
Albendazole
- cysticercosis
- echinococcus granulosus (cystic hydatid disease
- longer treatment duration 1-6 months risk of hepatotoxicity
What is praziqueantel contra-indicated in?
for treatment of ocular cysticercosis
-destruction of the organism in the eye may damage the eye itself
What is the drug of choice if there is a cystic hydatid disease due to Echinococcus granulosus (dog tapeworm in a human)?
Albendazole
-3 month treatment or longer
What is that one morphology thing that Fitzy pointed out about Schistosomiasis? (specifically, S. mansoni)
There’s a little spicule thing under microscopy
What is the drug of choice for all forms of Schistosomiasis?
Praziquantel
What does schistosoma present as?
Eggs in intestine
Flukes in the liver
Bioavailability of Praziquantel
- rapidly absorbed
- distributes into CSF
- metabolized
- Short half life
- extensive first pass metabolism
- extensive ptn binding
- inactive metabolites
What does praziquantel interfere with?
what does it cause?
calcium homeostasis
-causes falccid paralysis in adult flukes
What is necessary for praziquantel’s antithelminthic effect?
formation of specific antibodies
What does Praziquantel do exactly?
causes antigens within the parasite to be exposed to the action of host antibodies
What are the protozoal infections?
Amebiasis
Giardiasis
What are the anti-protozoal/antiamebic agents?
Metronidazole
Tinidazole
Nitazoxanide
What are the luminal amebicides?
Iodoquinol
Diloxanide furoate
Paromomycin
What is Metonidazole extensively used to treat?
infections caused by anaerobic organisms
- Protozoa and amoeba: Trichomonas vaginalis, entamoeba histolytica, giardia lamblia
- Bacteria: enterococcus species, clostridium
What is unique about the metabolism of the 3 protozoa and the anaerobic bacteria?
they do not rely on pyruvate dehydrogenase
-so they have pyruvate ferredoxin oxidoreductase (PFOR) complex
What activates metronidazole?
Pyruvate ferredoxin oxidoreductase (PFOR) complex
So, what is the drug of choice for amediasis?
Metronidazole
What drug is approved for the treatment of giardiasis as a single dose and is appropriate first-line therapy, considered to be superior to metonidazole?
Tinidazole
Adverse effects of Metronidazole/Tinidazole
- METallic taste
- Disulfiram-like reaction: severe symptoms associated with intake of alcohol and medication “disulfiram”
- abdominal distress, vomiting, flushing, headache
- alcohol-withdrawal symptoms
What are the therapeutic goals of treating Amebiasis?
- ) eliminate the invading trophozoites
2. ) eradicate intestinal carriage of the organism
What could E. histolytica be referred to in a question stem or answer choice if the test writer wants to be annoying?
A one-celled parasite
What doe E. histolytica present as?
loose feces, stomach pain, cramping
-severe symptoms from amebic dysentery include stomach pain, BLOODY stools, and fever
What does E. histolytica form in the liver?
abscess
-rarely spreads to other parts of the body like the lung and the brain
What is symptomatic, or invsive colitis treated with?
metronidazole followed by a luminal amebicide
What are some luminal amebicides that we could use?
paromomycin, diiodohydroxyquin, or diloxanide furoate
-to eliminate intraluminal cysts
What should asymptomatic patients with E. histolytic be treated with?
just an intraluminal agent alone…. makes sense
What is Paromomicin?
aminoglycoside family (not orally absorbed)
- Binds 30S ribosome of pathogen… disrupts protein synth
- Drug of choice for colonization of intestine with E. Histolytica
- alternative to metronidazole for E. histolytic infection during pregnancy
What should patients with Giardiasis be treated with?
tinidazole (bolded)
-or metronidazole, or nitazoxanide as the drugs of choice
What is Giardia lamblia?
a flagellated protozoan parasite, causes both epidemic and sporadic disease and is an important etiology of waterborne and foodborne diarrhea
What are the symptoms of Giardiasis?
diarrhea, malaise, steatorrhea, abdominal cramps, bloating, flatulence, nausea, and especially in young children, weight loss and failure to thrive
