Fitzpatrick: Parasitic, protozoa, C diff Pharm

Question 1

What drugs are used for nematodes?

Answer 1

Albendazole
Mebendazole
Pyrantel pamoate
Diethylcarbamazine
Ivermectin

Question 2

What drugs are used for Cestodes (tapeworms)?

Answer 2

Albendazole
Mebendazole
Praziquantel
Niclosamide

Question 3

What drugs are used for Trematodes?

Answer 3

Praziquantel

Question 4

What are the soil-transmitted helminths?

Answer 4

Ascaris
hookworm
trichuris

Question 5

What is used to treat these nematodes in endemic areas?

Answer 5

Albendazole

• Mebendazole is older
• these are both benzimidazoles

Question 6

MOA of benzimidazoles (Albendazole and mebendazole and Thiabendazole)

Answer 6

• 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…

Question 7

Where are nematodes usually residing?

Answer 7

the intestinal tract

Question 8

Why is mebendazole so great?

Answer 8

poor absorption, plus efficient metabolism, plus protein binding= LOW SYSTEMIC EXPOSURE
-so, it’s safe and effective :)

Question 9

How is Albendazole bioavailability and distribution?

Answer 9

modest absorption+EFFICIENT METABOLISM = low systemic exposure to parent drug
-safe and effects as a single dose

Question 10

Does albendazole itself have a lot of systemic exposure?

Answer 10

no, negligible

Question 11

What does abendazole get metabolized to that gets distributed a lot more places to kill tissue dwelling helminths, hydatid cysts?

Answer 11

Albendazole to Albendazole sulfoxide

Question 12

What does albendazole sulfoxide get metabolized to and what happens to it?

Answer 12

Albendazole sulfone

• inactive metabolite
• renal clearance

Question 13

Why is Thiabendazole only good for cutaneous use?

Answer 13

it has high systemic toxicity

-it’s good for larval migrans apparently

Question 14

Which anti-helminthic drug should be used for Enterobius vermicularis (pinworm)?

Answer 14

Mebendazole

Question 15

Which anti-helminthic drug should be used for Ancylostoma duodenale (Hookworm)?

Answer 15

Albendazole

Question 16

Ascaris lubricpoides?

Answer 16

Albendazole and Mebendazole

Question 17

Trichuris trichiura (whipworm)?

Answer 17

• Mebendazole
• Albendazole
• 3 day course most effective

Question 18

Toxocara spp

Larval migrans

Answer 18

Albendazole

Question 19

Why are we scared of albendazole and mebendazole in preggo people?

Answer 19

They are embryotoxic and teratogenic in preggo rats

-Pregnancy category C, not recommended in humans

Question 20

What is an alternative or adjunctive nematode therapy that is effective against hookworm, pinworm, and roundworm but INEFFECTIVE AGAINST TRICHURIS TRICHIURA?

Answer 20

Pyrantel pamoate

Question 21

What is in the NM junction of nematodes

Answer 21

N-AChR

-so they use acetylcholine a lot

Question 22

What is Pyrantel

Answer 22

a depolarizing NM blocking agent

-causes persistent activation of nicotinic acetylcholine receptors (N-AChR) and spastic paralysis of the worm

Question 23

What should we consider when we give pyrantel?

Answer 23

Worm burden

-they can get into places we don’t want them to be and clog up the joint

Question 24

What is the active ingredient in Pyrantel Pamoate?

Answer 24

• Pyrantel

- Pamoate is just the chewable component

Question 25

Pyrantel's bioavailability

Answer 25

Poorly absorbed from the GI tract - confines its action to intralumenal GI nematodes - less than 15% excreted in urine as parent drug and metabolite

Question 26

What ppl do we use Pyrantel with caution?

Answer 26

Pregnant women and children <2

Question 27

What was the other NEmatode/Helminth therapy we talked about?

Answer 27

Ivermectin

Question 28

What is Ivermectin used for?

Answer 28

intestinal strongloidyiasis- thread worm and Onchocerciasis- River Blindness

Question 29

What does Ivermectin do?

Answer 29

Activates Glutamate-Gated Chloride Channels - causes Cl-current - hyperpolarization - paralysis

Question 30

Can Ivermectin cross the BBB?

Answer 30

no | -so it won't mess with our GABA gated CL channels

Question 31

So, when is Ivermectin usually contraindicated?

Answer 31

When the Blood brain barrier is disrupted (meningitis, Trypanosomiasis)

Question 32

What has been the most extensive use for ivermectin in humans?

Answer 32

Onchoceriasis (River blindness) control in Africa - also useful for lymphatic Filariasis - Wuchereria bancrofti - Brugia malayi

Question 33

What is Diethylcarbamazine used for?

Answer 33

- Lymphatic filariasis | - Loasis

Question 34

What is bad about Diethylcarbamazine?

Answer 34

significant toxicity due to host-response following death of parasites

Question 35

What are the Cestodes that we have to worry about?

Answer 35

Cysticercosis Echinococcosis Taeniasis Diphyllobrothriasis

Question 36

When are people in an infective stage with Cysticercosis?

Answer 36

When they have EGGS in their stool

Question 37

When are people in the Diagnostic stage of cysticercosis?

Answer 37

When there are gravid proglottids in the feces

Question 38

What is the drug of choice for all adult form tapeworm infection?

Answer 38

Praziquantel

Question 39

What drug is used elsewhere but not in the US for tapeworm infections?

Answer 39

Niclosamide

Question 40

What is the drug of choice for LARVAL forms of tapeworm infections?

Answer 40

Albendazole - cysticercosis - echinococcus granulosus (cystic hydatid disease * longer treatment duration 1-6 months risk of hepatotoxicity

Question 41

What is praziqueantel contra-indicated in?

Answer 41

for treatment of ocular cysticercosis | -destruction of the organism in the eye may damage the eye itself

Question 42

What is the drug of choice if there is a cystic hydatid disease due to Echinococcus granulosus (dog tapeworm in a human)?

Answer 42

Albendazole | -3 month treatment or longer

Question 43

What is that one morphology thing that Fitzy pointed out about Schistosomiasis? (specifically, S. mansoni)

Answer 43

There's a little spicule thing under microscopy

Question 44

What is the drug of choice for all forms of Schistosomiasis?

Answer 44

Praziquantel

Question 45

What does schistosoma present as?

Answer 45

Eggs in intestine | Flukes in the liver

Question 46

Bioavailability of Praziquantel

Answer 46

- rapidly absorbed - distributes into CSF - metabolized - Short half life - extensive first pass metabolism - extensive ptn binding - inactive metabolites

Question 47

What does praziquantel interfere with? | what does it cause?

Answer 47

calcium homeostasis | -causes falccid paralysis in adult flukes

Question 48

What is necessary for praziquantel's antithelminthic effect?

Answer 48

formation of specific antibodies

Question 49

What does Praziquantel do exactly?

Answer 49

causes antigens within the parasite to be exposed to the action of host antibodies

Question 50

What are the protozoal infections?

Answer 50

Amebiasis | Giardiasis

Question 51

What are the anti-protozoal/antiamebic agents?

Answer 51

Metronidazole Tinidazole Nitazoxanide

Question 52

What are the luminal amebicides?

Answer 52

Iodoquinol Diloxanide furoate Paromomycin

Question 53

What is Metonidazole extensively used to treat?

Answer 53

infections caused by anaerobic organisms - Protozoa and amoeba: Trichomonas vaginalis, entamoeba histolytica, giardia lamblia - Bacteria: enterococcus species, clostridium

Question 54

What is unique about the metabolism of the 3 protozoa and the anaerobic bacteria?

Answer 54

they do not rely on pyruvate dehydrogenase | -so they have pyruvate ferredoxin oxidoreductase (PFOR) complex

Question 55

What activates metronidazole?

Answer 55

Pyruvate ferredoxin oxidoreductase (PFOR) complex

Question 56

So, what is the drug of choice for amediasis?

Answer 56

Metronidazole

Question 57

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?

Answer 57

Tinidazole

Question 58

Adverse effects of Metronidazole/Tinidazole

Answer 58

- METallic taste - Disulfiram-like reaction: severe symptoms associated with intake of alcohol and medication "disulfiram" - abdominal distress, vomiting, flushing, headache - alcohol-withdrawal symptoms

Question 59

What are the therapeutic goals of treating Amebiasis?

Answer 59

1. ) eliminate the invading trophozoites | 2. ) eradicate intestinal carriage of the organism

Question 60

What could E. histolytica be referred to in a question stem or answer choice if the test writer wants to be annoying?

Answer 60

A one-celled parasite

Question 61

What doe E. histolytica present as?

Answer 61

loose feces, stomach pain, cramping | -severe symptoms from amebic dysentery include stomach pain, BLOODY stools, and fever

Question 62

What does E. histolytica form in the liver?

Answer 62

abscess | -rarely spreads to other parts of the body like the lung and the brain

Question 63

What is symptomatic, or invsive colitis treated with?

Answer 63

metronidazole followed by a luminal amebicide

Question 64

What are some luminal amebicides that we could use?

Answer 64

paromomycin, diiodohydroxyquin, or diloxanide furoate | -to eliminate intraluminal cysts

Question 65

What should asymptomatic patients with E. histolytic be treated with?

Answer 65

just an intraluminal agent alone.... makes sense

Question 66

What is Paromomicin?

Answer 66

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

Question 67

What should patients with Giardiasis be treated with?

Answer 67

tinidazole (bolded) | -or metronidazole, or nitazoxanide as the drugs of choice

Question 68

What is Giardia lamblia?

Answer 68

a flagellated protozoan parasite, causes both epidemic and sporadic disease and is an important etiology of waterborne and foodborne diarrhea

Question 69

What are the symptoms of Giardiasis?

Answer 69

diarrhea, malaise, steatorrhea, abdominal cramps, bloating, flatulence, nausea, and especially in young children, weight loss and failure to thrive