Antiparasitics Flashcards
What class of drug is metronidazole?
Nitroimidazole
Why is metronidazole toxic to bacteria and parasites but not humans?
Pyruvate:ferrodoxin oxidoreductase reduces metronidazole in both prokaryotes. This metabolite is toxic and breaks DNA. In humans, however, the aerobic environment re-oxidizes metronidazole and thus eliminate its toxicity.
Note: this lecturer has metronidazole’s MOA as “enzyme unique to parasite.”
What are two drugs that are related to metronidazole?
Nitazoxanide and tinidazole
Tinidazole actually has fewer side effects and is better tolerated.
Metronidazole is contraindicated in what patients?
- First trimester pregnancy
- Renal insufficiency
- Hepatic insufficiency
- Alcoholics (because of disulfiram-like reaction)
Metronidazole is an ____________ of CYP450.
inducer
_____________ is commonly used to treat Cryptosporidiosis because it is poorly absorbed and can kill the parasites on the walls of the intestine.
Paromomycin
Also, visceral and cutaneous Leishmaniasis
There are two combinations that can treat Toxoplasmosis: ________________.
- pyrimethamine/sulfadiazine
* pyrimethamine/clindamycin
________________ selectively targets parasitic dihydrofolate reductase.
Pyrimethamine
Sulfonamides selectively target parasitic _____________.
dihydropteroate synthase (substrates PABA and pteridine)
Pentamidine also treats ______________.
Leishmaniasis and Trypanosomiasis
How does pentamidine work?
It isn’t fully agreed upon, but it might disrupt DNA.
Why is pentamidine given in inhaled form?
It is not absorbed orally.
List the three benzimidazoles.
- Thiabendazole (not used because of toxicity)
- Albendazole
- Mebendazole
How do the benzimidazoles work?
They inhibit microtubule formation, just like vincristine (think of Vin Diesel as the strong man bending the bar at the carnival).
Describe the important differences between mebendazole and albendazole.
- Mebendazole: not absorbed so concentrates in the gut; gets metabolized to inactive products; excreted in bile
- Albendazole: orally absorbed; distributes to tissues; requires hepatic metabolism for activation; excreted in urine
Because of the above properties, albendazole would be given for neurocysticercosis or hydatid cysts, while mebendazole would be given for intestinal nematodes.
How does pyrantel pamote work?
It is an acetylcholine receptor agonist. If it were given intravenously, it would cause paralysis. Fortunately, it is not well absorbed and can be given orally for Enterobiasis.
Ultimately, it concentrates in parasites and causes spastic paralysis.
List two contraindications for pyrantel pamote.
- Liver failure
* Someone taking piperazine
______________ is used for all cestode and trematode (fluke) infections exept hydatid cysts and neurocysticercosis.
Praziquantel
Although the mechanism of praziquantel is not known, it’s thought that ______________ may play a role.
damaging the integument of the parasite to induce an immune response
What two drugs can treat CNS Trypanosomiasis?
Melarsoprol and eflornithine
Remember that suramin is for the serum (i.e., the hematologic phase).
What drug treats Leishmaniasis?
Stibogluconate (like the T-bone steak)
When liver cells that have been infected with sporozoites rupture, they release ______________.
merozoites
The ____________ stage of Plasmodium is infectious to RBCs.
merozoite
What is a schizont?
A replication cycle
Which two forms of malaria can lie dormant?
P. vivax and P. ovale
How do the quinine antimalarials work?
Plasmodia metabolize nutrients in an acidic vacuole. When they break down hemoglobin, the heme portion produces oxidative species. The quinine drugs bind to heme and prevent it from polymerizing to its safe form, thus causing the accumulation of ROS.
During the febrile stage of malaria, high levels of quinine can be given because ________________.
high levels of alpha-1-acid glycoprotein are produced, which binds quinine
Note: because patients often get better with quinine, they down-regulate alpha-1-acid glycoprotein and can have cinchonism.
The army did not follow up on those given mefloquine (when it was developed at the Walter Reed Medical Center) and they missed that _______________.
mefloquine can cause psychotic disturbances
Malarone (atovaquone and proguanil) is very safe. But it can _____________.
interact with rifampin, cause rash, and induce nausea
_______________ also bind to heme and generate ROS.
Artemisinins
_____________ is the only drug effective against latent P. vivax or P. ovale.
Primaquine (like the primal queen not hypnotized)
True or false: metronidazole doesn’t get absorbed and is thus strictly a luminal agent.
False. It gets rapidly absorbed and distributes to all tissues, even the CSF.
How common is Toxoplasmosis?
50% of U.S. adults and 90% of French adults are seropositive by age 50
How does suramin work?
The mechanism is not fully known, but it’s thought that it may inhibit the parasite glucose metabolic pathway.
_____________ has a 1:2,000 incidence of life-threatening adverse effects.
Suramin
What antiparasitic was brought back on the market due to hair removal side effects?
Eflornithine (“It makes your skin as smooth as thE FLOoR.”)
What drug treats Strongyloides infection?
Ivermectin
What are two side effects among the benzimidazoles?
- Albendazole: cholestasis
* Mebendazole and albendazole: teratogens
Describe the pharmacokinetics of praziquantel.
- Rapidly absorbed
* 99% eliminated by the liver at the first go
A major contraindication to praziquantel is _______________.
ocular cysticercosis; the lysing of cestodes in the eye can lead to permanent ocular damage
The _____________ stage of P. falciparum and P. malariae is over in four weeks.
liver
P. falciparum is responsible for roughly ______% of malaria deaths.
85
When was quinine first used?
1633
High doses of quinidine can cause ______________.
hemolysis, tinnitus, and death
Atovaquone works by __________________.
disrupting pyrimidine synthesis
Proguanil gets metabolized to cycloguanil which is ____________.
DHFR inhibitor
