12 - Antiparasitic Drugs Flashcards
What approach is used for antiparasitic chemotherapy?
“Cure vs control”
-may have to eradicate multiple stages of parasite in host (adult, larval or immature stages, ova).
What are the different Nematode (roundworm) infections?
- Ascaris Lumbricoides
- Enterobius vermicularis (pinworm)
- Guinea worm
- Trichinosis
- Filariasis
- Strongyloides stercoralic (threadworm)
- Necator americanus (hookworm)
- Ancylostoma braziliense (dog hookworm)
- Toxocara canis
What is the general lifecycle of roundworms?
Adults in small intestines cause egg release in feces.
Rhabditiform larva hatches from egg.
Filariform larva grows and can penetrate skin (bare feet)
What are the four treatments for roundworm infections?
Mebendazole
Albendazole
Thiabendazole
Pyrantel pamoate
What drug treats many intestinal roundworms, kills some ova, is poorly absorbed, and has low systemic toxicity?
Mebendazole
What drug treats Echinococcus and cutaneous larval migrans? What are the side effects?
Albendazole.
Distributes well; causes elevated hepatic enzymes, abd. pain, nausea, vomiting, and headache.
What drug is effective against hookworm, pinworm, roundworm, not BOT for whipworm (trichuris)? What are side effects?
Pyrantel pamoate (OTC as Pin-X for pinworm).
Poorly absorbed, mild GI symptoms.
What oral or topical drug is used to treat strongyloides and cutaneous larva migrans from disseminated dog or cat hookworm? What are side effects?
Thiabendazole
Rapidly absorbed; causes nausea, vomiting, and dizziness.
What drug is the drug of choice for schistosoma and has some activity against other trematodes (flukes)? What are side effects?
Praziquantel
Can cause abdominal discomfort and nausea.
What are different organisms that cause cestode (tapeworm) infections?
- Taenia saginata
- Taenia solium
- Echinococcus granulosis, E. multilocularis (hydatid cysts)
- Diphyllobotherium latum
- Dwarf tapeworm
What is the general life cycle of a tapeworm?
- Eggs excreted in the environment and eaten by cattle (saginata) or pigs (solium).
- Eggs hatch and penetrate walls of intestines in animals and encyst in muscules and organs.
- We eat undercooked animal products and the scolex attaches and bore into our intestines and encyst in our brain or other organs.
- Sections loaded with tapeworms can break off into stool.
What drug is used to treat taenia solium because it also kills the the eggs (which are infective to main, and thereby prevet cysticercosis)?
Praziquantel
Good activity for many cestodes (tapeworms)
What is the agent of choice for neurocysticercosis?
Albendazole.
What drug is the 3rd choice for treatment of tapeworms and given to those who can’t tolerate praziquantel or albendazole?
Paromomycin sulfate.
What drugs can be used to prevent malaria?
None!
Antimalarial drugs only prevent progression to symptomatic malaria (this is what is meant by prophylaxis).
What is a characteristic of P. vivax and P. ovale infection? How long are these treated for prophylaxis?
They both remain in the liver as hypnozoites.
Target hepatic form for 14 days after leaving endemic area.
How should you treat malaria prophylactically?
For all four species, target RBC forms whine in the endemic area and continue for 4 weeks after leaving endemic area.
What drug is a blood schizonticide that causes parasitized erythrocytes to concentrate the drug >25 fold? How does it do this? What is the adverse effect?
Chloroquine
Does this be a pH-dependent mechanism into acidic vacuoles.
Can cause visual impairment.
What is the mechanism of action of chloroquine?
Chloroquine inhibits polymerization and degradation of hemoglobin in intraerythrocytic trophozoites, allowing heme to accumulate to toxic levels.
What are the uses of Chloroquine? What does and doesn’t it target?
Prevent attacks of all 4 species of malaria, provided they are sensitive.
-not effective on chloroquine-resistant strains of P. falciparum and P. vivax
Can eradicate P. malariae and sensitive P. falciparum.
Targets blood schizonts of P. vivax or ovale but does NOT target liver hypnoziotes.
What drug has a similar MOA to chloroquine and is a blood schizont? What does it treat?
Mefloquine.
Treats Chloroquine-resistant P. falciparum and P. vivax.
Prophylaxis in chloroquine-resistant areas.
What are side effects and contraindications of Mefloquine?
Contraindicated in those with epilepsy or psychiatric disorders.
Black box warning for psychiatric effects such as anxiety, paranoia, and depression. Vestibular effects such as dizziness and vertigo.
What drugs work by blocking pyrimidine synthesis? What is the MOA of each drug?
Atovaquone + proguanil
Atovaquone: selectively inhibits malarial mito electron transport (cyt bc1) to disrupt pyrimidine synthesis.
PRoguanil: inhibits malarial dihydrofolate reductase to block folate synthesis and ultimately pyrimidine synthesis.
What are the uses of atovaquone + proguanil? What are the side effects?
Prevention and treatment of chloroquine-resistant P. falciparum.
Nausea, diarrhea, vomiting, and rash.
What drug is similar to chloroquine and is a blood schizonticide used for all for malarial parasites and for severe acute attacks? What can this treat?
Quinine
Can be used on chloroquine-resistant P. falciparum.
What are the side effects of Quinine?
Cinchonism: headache, visual disturbances, dizziness, tinnitus.
Gastric irritation, nausea, vomiting.
Cardiac effects similar to quinidine. (IV no loner available in US, only oral).
What drug decreases malarial protein synthesis by depressing dihydroorotate dehydrogenase activity and thereby interfering with pyrimidine synthesis?
Doxycycline.
What can doxycyline be used to treat?
Multi-drug resistant P. falciparum
Prophylaxis of chloroquine-resistant P. falciparum
What drug can kill liver hypnozoites and is a radical cure/terminal prophylaxis for P. vivax and P. ovale? What else can it be used to treat?
Primaquine - should be used in combo with blood schizonticide.
Can be used with clindamycine for pneumocystis jiroveci pneumonia in AIDs pts.
What are the side effects of primaquine?
Hemolytic rxns in those with G6P dehydrogenase deficiency
-Primaquine-mediated hemolysis led to discovery of G6PD deficiencies
CDC recommends only giving to pts with normal documented G6PD
What is the most common causative agent of amebic dysentary?
Entamoeba histolytica.
What are the anatomical sites of action of drugs that treat amebic dysentary caused by entamoeba histolytica?
- Tissue Amebicides: for symptomatic infections
2. Luminal amebicides: used alone for asymptomatic infections or with tissue amebicide for symptomatic infections.
What drug is a tissue amebicide? What drugs are luminal amebicides?
Tissue: metronidazole
Luminal: iodoquinol, paromomycin sulfate
What is the life cycle of entamoeba histolytica?
Mature cysts are consumed and then shed in the feces. They can also cause extraintestinal disease in other parts of the body.
Eggs are shed in feces.
What luminal amebicide causes diarrhea, GI symptoms, and is contraindicated in those that are hypersensitive to iodine?
Iodoquinol
What luminal amebicide is an aminoglycoside that inhibits protein synthesis? How is it given? What are side effects?
Paromomycin sulfate.
Oral dose poorly absorbed = low incidence of systemic side effects.
Causes diarrhea, nausea, vomiting, and epigastric pain.
What protozoal disease can metonidazole treat?
Giardia lamblia
Trichomonas vaginalis
What drug can treat giardia lamblia and cryptosporidium parvum?
Nitazoxanide
What is the NOA of nitazoxanide? What are side effects?
Inhibits pyruvate: ferredoxin oxidoreductase and disrupts anaerobic energy metabolism.
Causes diarrhea, nausea, and abdominal pain.
What drug works as prophylaxis and treatment for pneumocystis jiroveci and treats toxoplasma gondii?
Atovaquone
What drugs can be used to treat Pneumocystic jiroveci?
TMP-SMX
Clindamycine + primaquine
Atovaquone
Dapsone
