Chapter 36- Antiparasitics Flashcards
What is the clinical application of chloroquine
Malaria, all species
What are some adverse reactions seen with chloroquine
Retinopathy, prolonged QT interval, methemoglobinemia, pruritis
What is a contraindication to chloroquine use
Visual field changes
What is the exact mechanism of action of chloroquine
Protonated chloroquine accumulates inside the parasite’s food vacuole, where it binds to ferriprotoporphyrin IX (heme) and inhibits its polymerization
What stage of plasmodia infections does chloroquine kill
Erythrocytic stage only
What is the clinical application of quinine (quinidine)
Malaria, especially P. Falciparum
What antimalarial agent that is an inhibitor of heme metabolism can cause cinchonism (tinnitus, deafness, headaches, nausea, vomiting, visual disturbances)
Quinine
What are some contraindications for quinine use
G6PD, myasthenia gravis
What specific type of malaria is quinine used for
Acute blood-stage malaria, but not used prophylactically
What is the clinical application of mefloquine
Chloroquine-resistant malaria
What anti-malarial agent that inhibits heme metabolism has neuropsychiatric symptoms
Mefloquine
What are is the proposed mechanism of mefloquine
Appears to disrupt polymerization of heme to hemozoin inside intraerythrocytic malarial parasites
What is the mechanism of action of primaquine
Disrupts metabolism in plasmodia mitochondria, likely by inhibiting ubiquinone and by non-specific oxidative damage
What is the clinical application of primaquine
P. Vivax and P. Ovale (attacks hepatic form)
What is a contraindication for primaquine
G6PD- it crosses placenta and DNA induce fatal hemolysis in fetal erythrocytes independent of maternal G6Pd status
What antimalarial drug can also target toxoplasmosis and babesiosis
Atovaquone
What is the mechanism of action of atovaquone
Inhibits the interaction between reduced ubiquinone and the cytochrome Bc1 complex (disrupts pyrimidine synthesis)
What analogues are sulfadoxine and sulfalene
PABA analogues that competitive inhibit plasmodial dihydropteroate synthetase
What analogue is pyrimethamine
Folate analogue that competitively inhibits plasmodial dihydrofolate reductase
What stage of P. Falciparum infection is sulfadoxine/sulfalene-pyrimethamine effective against
Schizont stage
What is the contraindication for proguanil use
Prophylaxis of P. Falciparum malaria in patients with severe renal impairments
What does proguanil inhibit
Pyrimidine derivative that inhibits plasmodial dihydrofolate reductase
What is proguanil primarily effective against
Hepatic, pre-erythrocytic forms of P. Falciparum and P. Vivax
What is the clinical application of metronidazole and tinidazole
Anaerobic bacterial, amebiasis, giardiasis, trichomoniasis
What are some adverse reactions seen with metronidazole/tinidazole
Disulfiram-like efffect with alcohol; headache, metallic taste, vaginitis
What is the clinical application of nitazoxanide in kids
Giardiasis
What is the clinical application of nitazoxanide in adults
Crytosporidiosis
What is the mechanism of action of nitazoxanide
Inhibits the pyruvate-ferredoxin oxidoreductase (PFOR) enzyme that converts pyruvate to acetyl CoA in Protozoa and anaerobic bacteria
What is the clinical application of pentamidine
African trypanosomiasis; pneumocystis carinii pneumonia
What is the mechanism of action of pentamidine
Inhibits DNA, RNA, protein and phospholipid synthesis, and dihydrofolate reductase activity
What is the clinical application of suramin
Early stage African trypanosomiasis
What are some adverse reactions seen with suramin
Pruritis, paresthesias, vomiting, nausea
What is the mechanism of action of suramin
Inhibits RNA polymerase and glycerol phosphate dehydrogenase (interferes with parasite replication)
What is the clinical application of metarsoprol
Late stage African trypanosomiasis
What are some adverse reactions seen with metarsoprol
Reactive encephalopathy, death, phlebitis
What is the clinical application of eflomithine
West African trypanosomiasis (IV); hair removal (topical_
What is the mechanism of action of efomithine
Selective and irreversible inhibitor of ornithine decarboxylase
What is the clinical application of nifurtimox
New world trypanosomiasis (chagas disease)
What are some adverse reactions seen with nifurtimox
Pancytopenia, neuropathy, convulsions memory loss
What is the mechanism of action of nifurtimox
Generates toxic intracellular oxygen radicals in the parasites
What is the clinical application of sodium stibogluconate and meglumine antimonate
Leishmaniasis
What is the mechanism of action of ivermectin
Potentiates both glutamate gated chloride channels in nematode cell membranes and release of GABA from pre-synaptic terminals
What is the clinical application of ivermectin
Onchocerciasis, lymphatic filariasis, strongyloidiasis, scabies, cutaneous larva migrants
What is the mechanism of action of anbendazole, mebendazole, thiabendazole
Inhibit tubulin polymerization by binding to beta tubulin
What is the clinical application of albendazole, mebendazole, thiabendazole
Nematode infections, cysticercosis, echinococcosis
What is the mechanism of action of praziquantel
Increase parasites membrane permeability to calcium which leads to contraction and paralysis of worms
What is the clinical application of diethylcarbamazine
Filariasis
What excretes diethylcarbamazine
Kidney
What is the clinical application of pyrantel pamoate
Pinworm, roundworm, and hookworm infections
What is the mechanism of action of pyrantel pamoate
Causes constant release of acetylcholine, leading to persistent activation of parasite nicotinic acetylcholine receptors, leading to tonic paralysis
What is the clinical application of piperazine
Roundworm infection
What is the mechanism of action of piperazine
GABA agonist, leading to flaccid paralysis (rarely used)
