Parasitic Agents Flashcards
Malaria in the blood
Schizont
Malaria is the liver
Merozoites
What malaria drug works on the liver
Primiquine
What malaria drugs works on the blood cycle
chloroquine and Artemisinins
Drugs used for prophylaxis of malaria
Primaquine and Chloroquine
Drugs used for treatment of malaria
Artemether/lumefantrine, Chloroquine, Primaquine
What 2 drugs have significant gametocidal activity
Artemether and primaquine
T/F: Blood stage antimalarials are ineffective against liver stage parasites
True
T/F: We have drugs against sporozoites therefore we have a “true prevention”
False
What malarial drug is a weak base that becomes trapped in acidic parasite food vacuoles (trapped in infected RBC). Digestion of hemoglobin liberates heme (hematin), which is toxic to the parasite. Inhibits biocrystallization
Chloroquine
Resistance to chloroquine is due to
Mutated vacuolar efflux transporter (PfCRT)
Therapeutic uses of chloroquine
Ineffective against most strains. Prophylaxis and treatment against sensitive strains during pregnancy
Adverse rxns of chloroquine
Generally well tolerated for prophylaxis. Can cause pruritis, headache, and GI effects in treatment doses. High doses cause CV toxicity.
Name an Artemisinins
Artemether- derived from chinese medicinal plant qinghao.
MOA of artemether
Unclear- evidence suggests artemisinins are converted to toxic free radicals by heme
Artemether has a _______ half life ________ absorbed in the GI tract so not useful for chemoprophylaxis.
Short, rapid
Systemic antiprotozoal agent
Metronidazole- a prodrug that is converted to a DNA-damaging metabolite by anaerobic organisms
Luminal antiprotozoal agent
Paromomycin
Benzimidazole
Albendazole
MOA of albendazole
Inhibits polymerization of parasite B-tubulin, preventing formation of cytoplasmic microtubules. Disrupts nematode motility and DNA replication. First pass metabolism to active form, albendazole sulfoxide.
What drug is this?: Generally used in combo with other antimalarials. Fixed dose combo with lumefantrine which sustains antimalarial activity. A first line oral treatmnt of MDR faciparum malaria in endemic areas.
Artemether
Adverse rxns of artemether
Safe reputation but:
1) Neurotoxicity
2) Potent embryotoxicity in animal models; humans unclear
MOA and Therapeutic uses for primaquine
MOA: Unclear
Therapeutic: With chloroquine to achieve clinical and radical cure of vivax/ovale malaria. Terminal prophylaxis after completion of travel to vivax/ovale endemic areas. Primary prophylaxis against all species if other agents are inappropriate.
Adverse effects of primaquine
Generally well tolerated in G6PD deficiency normal patients.
Prototype for drug-induced hemolytic anemia in G6PD deficiency.
Contraindicated in all G6PD deficient patients and in pregnant women.
Therapeutic uses of metronidazole
Amebiasis, giardiasis, trichomoniasis. For amebiasis- given in combination with a luminal amebicide to eradicate luminal survivors.
MOA of paromomycin
Aminoglycoside that binds to 30S ribosomal subunit of E.histolytica to inhibit protein synthesis; not absorbed from GI tract so is not effective systemically.
Therapeutic uses of paromycin
Alone for asymptomatic amebiasis or in combo with metronidazole for amebic colitis/dysentery.
Alternative to metronidazole during 1st trimester in pregnant females being treated for giardiasis.
Therapeutic uses for albendazole
Cestode infections
Roundworm infections
Pinworm infection
Adverse rxns of albendazole
Teratogenic effects in animals; use should be avoided in pregnancy.
Long term use can cause liver toxicity
MOA, Therapeutic uses, and adverse rxns of Praziquantel
MOA: Increases permeability of trematode and cestode cell membranes to calcium; results in paralysis, dislodgment, and death.
Therapeutic: Drug of choice for schistosomiasis and effective in treatment of most other trematode and cestode infections.
Adverse rxns: Generally well tolerated- not sure if symptoms (fever, pruritis, rash) are from drug or release of proteins from worm death.
MOA for Pyrantel pamoate
Depolarizing neuromuscular blocking agent. Only effective in GI tract because poor absorption. Causes persistant activation of parasite nicotinic ACh receptors and inhibition of AChE; results in spastic paralysis followed by expulsion of the worms.
Therapeutic uses for pyrantel pamoate
Available OTC and alternative to albendazole for ascariasis and enterobiasis
Adverse rxns of pyrantel pamoate
Generally well tolerated- will produce neuromuscular blockade if given parenterally
MOA for ivermectin
Immobilization of worms by tonic muscle paralysis.
a) Activates glutamate-gated Cl- channels found only in invertebrates.
b) causes hyperpolarization of cell membrane
c) P-glycoprotein efflux transporter pumps the drug out of mammalian CNS
Therapeutic uses for Ivermectin
Broad spectrum agent used to treat infections by nematodes and arthropods in veterinary med.
Onchocerciasis (river blindness), lymphatic filariasis and intestinal nematodes in humans.
Adverse rxns for Ivermectin
Generally well tolerated
- Mazzotti rxn- pruritis, rash, fever, lymphadema due o immune reaction to dying worms.
- Teratogenic (cleft palate) in animal studies- should be avoided in pregnancy
Effective drugs against Pinworm
Benzimidazole or Pyrantel pamoate
Effective drug against threadworm
Ivermectin
Effective drug against Tapeworms and/or flukes
Praziquantel
