Parasite Pharmacology - Burkin Flashcards
What are the characteristics of protozoa?
- eukaryotic
- 80S ribosomes
- cholesterol in membrane
- no cell wall
- metabolic pathways similar to animal cells
- VERY SIMILAR TO HUMAN CELLS
Name the anti-malarial drugs.
- quinine
- chloroquine
- primaquine
- antimetabolites
Name some other anti-protozoal drugs.
- metronidazole
- diloxanide
- nifurtimox
- suramin
What drugs are effective against the malaria parasite when it is in the mosquito?
The sporontocides:
- primaquine
- proguanil
- pyrimethamine
What drugs are effective against the malaria parasite when it is in human tissue?
The tissue schizontocides:
- primaquine
- proquanil
- pyrimethamine
- tetracycline
What drugs are effective against the malaria parasite when it is in human blood?
The blood schizontocides:
- chloroquine
- quinine, quinidine
- mefloquine
- artesunate
- sulfadoxine + pyrimethamine
- halofantrine
- tetracycline
What is quinine used for?
Used to treat chloroquine resistant Plasmodium falciparum.
What is the MOA of quinine?
It blocks heme polymerization. This leads to toxic build up in RBC and destruction of the RBC.
What are the adverse affects of quinine?
- cinchonism - like an overdose effect that can cause hemolytic anemia
- curare effect - paralysis and vasodilation
- myocardial depression
- vasodilation
- hemolytic anemia
What is Chloroquine used for?
- prophylaxis
- amebiasis
- acute malarial attacks
What is the MOA of Chloroquine?
It blocks plasmodial heme polymerization, increases heme concentrations which is toxic to the parasite.
What form of the parasite is sensitive to chloroquine?
The erythrocytic form. Is not effective against hypnozoites.
What are the adverse reactions of Chloroquine?
- prophylaxis - little toxicity
- Acute - anorexia, nausea, vomiting, headache, hemolytic anemia
- Amebicidal doses - photosensitization, retinopathy , leukopenia
- do not take with anti-diarrheals because makes chloroquine less effective
What is Primaquine used for?
Used to treat latent liver forms of P. vivax and P. ovale. Also effective for blood stages of parasite.
What is the MOA of Primaquine?
Binds to DNA, damages mitochondria and inhibits protein synthesis.
What are the adverse effects of Primaquine?
- same as chloroquine
2. hemolytic anemia
Why should the use of anti-malarials be limited and monitored in G6PD deficient pt’s?
G6PD pt’s are deficient in the G6P dehydrogenase enzyme. This enzyme is important in preventing oxidative stress in RBC’s. Some anti-malarials such as primaquine and chloroquine cause hemolytic anemia and their use in G6PD deficient patients would make their anemia worse.
Why should the use of anti-malarials that cause hemolytic anemia not be used in pregnant women?
The baby is relatively G6PD deficient and can become anemic.
What is Primethamine-Sulfadoxine or Fansidar used for?
Used to treat chloroquine resistant P. falciparum.
What is the MOA of Primethamine-Sulfadoxine?
Inhibits folic acid synthesis in the malaria parasite by inhibiting the parasite dihydrofolate reductase. Folic acid is needed for DNA and RNA synthesis.
What are the adverse reactions of Pyrimethamine-sulfadoxine?
- can cause kinecterus or bilirubin build up in fetuses
- hemolytic anemia
- Stephens-Johnson syndrome - skin peels off
- contraindicated in pregnant women and G6PD deficient pt’s
What is Mefloquine used for?
- MDR P. falciparum infection
- MOA thought to be blockage of heme polymerization
- can cause neurologic effects - acute psychosis, transient encephalopathy and convulsions
What is Atovaquone + chloroguanide used for?
- MDR P. falciparum infection
- MOA - inhibits malarial DHFR, affects folic acid synthesis
- can cause diarrhea, vomiting, kidney failure, affects human folic acid synthesis
What are Artemisinin derivatives used for?
- standard treatment of P. falciparum
- MOA - oxidative stress in malarial parasite
- can cause nausea, vomiting, anorexia, dizziness and possible allergic Rx
What are Tetracylines used for?
- Doxycyline used for prophylaxis
2. contraindicated for pregnant women, hepatic dysfunction pt’s, children under 8 years old
What is metronidazole used for?
- Amebiasis, trichomoniasis, giardiasis
2. Anaerobic bacterial infections
What is the MOA of metronidazole?
Activated only in anaerobes to metabolites that damage DNA.
What are the adverse effects of metronidazole?
- GI distress
- seizures and neuropathy
- potential mutagen
- Disulfiram effect - makes sick if used with alcohol
- contraindicated if pregnant
What is Nifurtimox used for?
- treatment of Chagas disease
- MOA - oxidative damage to DNA
- causes GI effects, vertigo, insomnia , rashes
What is Suramin used for?
- Treatment of African trypanosomiasis
- MOA - inhibits multiple enzymes
- causes GI effects, neurological effects, hematopoietic effects
What are the therapeutic strategies of antihelminthic drugs?
- inhibit muscle contraction
- inhibit energy metabolism
- limit distribution of generally toxic drugs
What is praziquantel used for?
- treatment of cestode and fluke infection - broad spectrum
- causes calcium influx and muscle contraction of smooth muscle of worm. This causes antigenic structures to be exposed to immune system.
- may cause nausea, vomiting and abdominal pain
What is Bithionol used for?
- lung and liver fluke infections
- alternative to praziquantel
- may cause nausea, vomiting, diarrhea, rashes and photosensitization
What are some alternative drugs used to treat fluke infections?
- Metrifonate (cholinesterase inhibitor) - treat S. hematobium
- Oxamaquine - treat S. mansoni
- Niridazole - treat S. mansoni and S. hematobium
What is Mebendazole used to treat?
- Trichuriasis, capillariasis, hookworm infection, echinococcosis, enterobiasis, ascariasis
- MOA - binds to tubulin and disrupts microtubule function
- low toxicity but poorly absorbed
- potential teratogen - contra indicated for pregnant women
What is Albendazole used for?
- treat Strongyloidiais, Trichurasis, capillariasis, ascariasis, filariasis, toxocariasis, hydatid disease, cystercercus cellulosis, taenium solium
- MOA - disrupts microtubule function
- can cause GI discomfort and headache
- potential teratogen - contraindicated in pregnant women and one month before becoming pregnant
What is Thiabendazole used for?
- treat strongyloidiasis and nematode larval infections
- MOA -blocks helminth specific enzyme fumarate reductase, disrupts microtubule function also
- high incidence of nausea, vomiting and anorexia
What is Diethylcarbamazine used for?
- treatment of tissue and blood nematodes - Filariasis
- MOA - enhances immune response
- can cause headache, malaise, nausea and inflammation
What is Ivermectin used for?
- Nematode infections - onchocerciasis, enterobius, strongyloides, trichuris and ascaris
- MOA - tonic paralysis of musculature by activating glutamate coupled Chloride channels
3 usually well tolerated
