Chapter 11: Antiparasitic drugs
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| Malaria |
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| what are the four species of organisms that can cause malaria? | plasmodium vivax, plasmodium ovale, plasmodium malariae, plasmodium falciparum
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| which species of malaria causes the most devastating and deadly form of malaria? | plasmodium falciparum
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| when traveling to an endemic area, what is the key thing to do to prevent getting malaria | prophylaxis
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| prophylactic agents for malaria are determined how? | determined by the region to which one is traveling, which largely determines whether one is going to a chloroquine resistant area of the world or not.
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| chloroquine resistance has primarily developed in which species of malaria | plasmodium falciparum (the deadliest kind)
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| if malaria is acquired, treatment is based upon what? | what species is definitively causing the infection.
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| if one is infected with p. vivax, or p.ovale, what drug in addition to anti malarial treatment must they receive? why? | primaquine. because these two species form hypnozoites (latent forms) in the liver that are not killed by standard malarial treatment. THe hypnozoites will cause recurrent symptoms later when viable hypnozoites become metabolically active.
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| this drug destroys hypnozoites | primaquine
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| what are the drugs for prophylaxis in areas where malaria is chloroquine sensitive? what if woman is pregnant? | chloroquine or atovaquone-proguanil. chloroquine is the drug of choice for these situations in which the patient is pregnat.
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| what is the drug of choice for areas with chloroquine resistance? what if patient is pregnant? | atovaquone/proguanil. second line agents include mefloquine, doxycycline. if pt. is prgnant, mefloquine is the DOC.
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| this drug is a protein synthesis inhibitor, it discolors developing teeth and bones, and so cannot be used in children less than 8 years old or in pregnant women. | doxycycline
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| what are some serious adverse effects of mefloquine? | MI when used in combination with quinines, drug induced psychosis, seizures, retinal damage, G6PD exacerbation.
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| mefloquine is contraindicated in which patients? | those with GAD, MDD, seizur disorder.
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| what is the MOA of atovaquone? | acts as a ubiquinone analog, thereby selectively inhibiting the protozoans mitochondrial ETC, effectively limiting the organisms ability to undertake ATP synthesis. teratogenic.
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| what is the MOA of chloroquine? | poisons organisms, causing physical destruction to them, starving them, and inhibiting their DNA syntehsis.
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| what is the DOC for chloroquine resistant p.falciparum? | quinine + one of the following: (doxycycline, tetracycline, clindamycin). also can use atovaquone-proguanil or mefloquone if chloroquine resistant.
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| if a patient with chloroquine rsistant p.falciparum infection is pregnant, what is the drug of choice? | quinine plus clindamycin.
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| what is the DOC for treating malaria caused by chloroquine resistant p vivax? | qunine plus either doxycycline or tetracycline plus primaquine. equally effective alternative agents include mefloquine plus primaquine.
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| what is the DOC for pregnant women with p.vivax? | quinine alone (no primaquine)
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| any malarial infection caused by p.vivax or p.ovale must also be treatd with what? | primaquine (unless patient is pregnant)
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| what are the four ways chloroquine kills malaria? | 1. transforms heme into a toxin 2. forms complexes with plasmodia and the RBCs that contain plasmodia 3. alkalizes plasmodia food vacuoles, starving the orgnaism 4. inhibits plasmodia DNA synthesis.
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| what is the MOA of quinine? | inihibits plasmodium DNA synthesis.
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| what is an adverse effect of quinine? | causes cinochism (tinnitis, photophobia, mental dullness, depression, confusion, headache, nausea)
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| what is the MOA of primaquine? | prevent malaria relapse by killing any malarial orgnaisms in the liver. also prevents gametocyte formation (the stage of organism taken up by biting mosquitos), and therefore prevents malaria spread
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| what is the MOA of Artemether? | combined with lumefantrine, and is used as another option for treatment of chloroquine resistant p.falciparum or chloroquine resistant. p.vivax. cheap.
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| other protozoa |
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| what is the DOC for treatment of trichomoniasis (trichomoniasis vaginalis) and amoebiasis (Entamoeba Histolytica) | metronidazole. can also be used as an alternative drug for treatment of giardia lamblia. it acts as an electron acceptor, creating compounds that readily bind the organisms proteins and DNA, causing the organisms death. can cause a disulfiram-like rxn.
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| what is an alternative DOC for entamoeba histolytica? | tinidazole. it has the same MOA as metronidazole, but has a better side effect.
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| what is the DOC for giardiasis | tinidazole
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| what is the DOC for leishmania donovani? | stibogluconate
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| what is the MOA for stibogluconate? | inhibits glycolysis, so the organism is unable ot use glucose an dies.
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| what is the DOC for systemic infeciton with Leishmania? | Amp B
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| what is the DOC for early stage stage East African sleeping sickness caused by trypanosoma brucei rhodensiense. | suramin
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| what is the MOA of suramin? | reacts with a number of metabolic enzymes of the target organism, espeicallyl glucose-6-phosphate dehyedrogenase, resulting in cellular destruction. does not cross the BBB.
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| what is the DOC for west african sleeping sickness caused by trypanosoma brucei gambiense | pentamidine causes pruritis and fever.
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| what is the MOA for pentamidine? | inhibit topoisomerase, prohibiting the organism from using its own DNA. it is nephrotoxic, causes pancreatitis and hypotension
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| this is used a s the treatment for all forms of africal sleeping sickness (late stage). it is only first line for late stage east african sleeping sickness. reacts iwth sulfhydryl groups in the organims and humna. | melarsoprol
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| used as a first line treatment for lat stage west african sleeping sickness, preferred over melarsoprol for this form of sleeping sickness. inhibits ornithine decarboxylase | eflornithine
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| these are the drugs of choice for treatment of chagas disease. both work to create radical oxygen species that destroy enzymes, killing the organism. | benznidazole, nifurtimox
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| this is the DOC ofr cryptosporidiosis and giardiasis. | nitazoxanide. it is a prodrug rapidly converetd to its active metabolite.
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| this is the DOC for treatment of infetions iwth pneumocystis jiroveci, and cyclospora cayetanensis. work by inhibiting folate manufacture and use, inhibits DNA synthesis. | trimethoprim-sulfamethaxazole. trimethoprim causes megaloblastic anemia
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| TMP-SMX is also a DOC for prophylaxis against what agent? | toxoplasma encephalitis.
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| this is the DOC for treatment of infections iwth pathologic amoeba, naegleria fowleri. this is an aggressive and deadly amoeba | amphotericin B. although it is an antifungal, it is the only drug known to work against this agent.
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