Pharm 36 Parasitic Infections Flashcards
Chloroquine
Antimalarial Agent: decrease the metabolism and/or remove toxic heme products, resulting in inc toxicity to the plasmodia.
Used for all species of malaria
Contraindications: visual field changes
Protonated chloroquine accumulates inside the parasite’s food vacuole, where it binds to ferriprotoporphyrin IX (heme) and inhibits its polymerization, accumulation of this leads to oxidative membrane damage.
Kills only erythrocytic stage of plasmodial infections.
Quinine, Quinidine
Anitmalarial Agent: dec the metabolism and/or remove toxic heme products, resulting in inc toxicity to the plasmodia.
Used for: malaria (esp P. falciparum)
Contraindications: G6PD deficiency, myasthesnia gravis
Mech similar to chloroquine but also intercalates into DNA.
Used to treat acute blood-stage malaria but not prophylactic
Mefloquine
Anitmalarial Agent: dec the metabolism and/or remove toxic heme products, resulting in inc toxicity to the plasmodia.
Used for: Chloroquine-resistant malaria
Contraindications: depression, anxiety, schizophrenia
Disrupts polymerization of heme to hemozoin inside intraerythrocytic malarial parasites.
Artemisinin, Artesunate, Artemether, Dihydroartemisinin
Anitmalarial Agent: dec the metabolism and/or remove toxic heme products, resulting in inc toxicity to the plasmodia.
Used for all species of malaria
Form carbon-centered free radicals that alkylate heme.
First line therapy for malaria w/ secondary agent.
Can be used IV
Primaquine
Antimalarial Agent: Inhibits electron transport
Uses: P. vivax, P. ovale
Contraindications: G6PD deficiency, PREGNANCY, bone marrow suppressants, RA, lupus
Disrupts metabolism in plasmodial mitochondria by inhibiting ubiquinone and by oxidative damage. Kills liver and erythrocyte-stage malaria
Atovaquone
Antimalarial Agent: Inhibits electron transport
Uses: P. falciparum, toxoplasmosis, babesiosis
Inhibits interaction between reduced ubiquinone and the cytochrome bc1 complex.
Used in combo with proguanil or doxycycline
Doxycycline, Tetracycline, Clindamycin
Antimalarial Agent: inhibits translation. Inhibits protein synth. by binding to 30S subunit (dox and tetra) or 50S (clinda)
Uses: all species of malaria
Cannot be taken during last half of pregnancy or children under 8 years old (dox and tetra)
With quinine can be used for chloroquine-resistant P.falciparum
Sulfadoxine-pyrimethamine, sulfalene-pyrimethamine
Antimalarial Agents: Inhibitors of folate metabolism
Uses: P. falciparum
Contraindications: blood dyscrasias, infants less than 2 mo, pregnant or breast feeding, liver or renal disease
Sulfadoxine and sulfalene are PABA analogues that competitively inhibit plasmodial dihydropteroate synthetase.
Pyrimethamine is a folate analogue that competitively inhibits plasmodial dihydrofolate reductase.
Proguanil
Antimalarial Agents: Inhibitors of folate metabolism
Uses: all species of malaria
Contraindications: severe renal disease
Pyrimidine derivative that inhibits plasmodial dihydrofolate reductas.
Primarily active against the hepatic, pre-erythrocytic forms of P. falciparum and P. vivax.
Used with chloroquine and atovaquone
Metronidazole, Tinidazole
Antiprotozoal Agents
Used for: Anaerobic bacteria, Amebiasis, Giardiasis, Trichomoniasis
Contraindications: hypersensitivity to parabens, first trimester, alcohol use
Metronidazole is activated by enzymes in parasites and anaerobic bacteria to form reduced cytotoxic compounds that damage microbial proteins, membranes and DNA.
Tinidazole is a second-gen nitroimidazole related to metra, but is better tolerated and needs shorter duration of treatment
Pentamidine
Antiprotozoal Agents
Uses: African trypanosomiasis, Pneumocystis carinii (jiroveci) pneumonia
Inhibits DNA, RNA, protein, and phospholipid synthesis, and dihydrofolate reductase activity.
Has a high affinity for DNA in kinetoplasts and suppresses kinetoplast replication and function.
Second line treatment Pneumocystis carinii (jiroveci) pneumonia
Suramin
Antiprotozoal Agents
Uses: Early stage African trypanosomiasis
Inhibits RNA polymerase and glycerol phosphate dehydrogenase
Melarsoprol
Antiprotozoal Agents
Uses: Late stage African trypanosomiasis
Inhibits trypanosomal pyruvate kinase, thereby inhibiting glycolysis and decreasing ATP production; also inhibits adenine and adenosine uptake by trypansomal transporters
Treatment can be associated with 4-6% death rate (reactive encephalopathy).
Coadministered with corticosteroids lessens the likelihood of reactive encephalopathy.
Coadministration with thiamine lessens chance of polyneuropathy.
Eflornnithine
Antiprotozoal Agents
Uses: West African trypanosomiasis (IV), hair removal (topical)
Selective irreversible inhibitor of ornithine decarboxylase.
Nifurtimox
Antiprotozoal Agents
Uses: Chagas’ disease (new world trypanosomiasis)
Generates toxic intracellular oxygen radicals in the parasite; mammalian cells are protected by the activity antioxidant enzymes such as catalase, glutathione peroxidase, and superoxide dismutase.
Sodium stibogluconate, Meglumine antimonate
Antiprotozoal Agent
Uses: Leishmaniasis
Inhibits the glycolytic pathway and fatty acid oxidation
Miltefosine
Antiprotozoal Agent (also antineoplastic, immunomodulatory)
Uses: Visceral leishmaniasis (oral), cutaneous lymphomas and skin metastases from breast cancer (topical)
Contraindications: pregnancy, breastfeeding, radiation therapy, large deep metastases
Synthetic ether phospholipid analoge similar to phospholipids in cell membranes.
May inhibit enzymes associated with plasma membranes (protein kinase C) and phosphatidylcholine biosynthesis.
Inhibit platelet activating factor-induced responses and inositol phosphate formation.
Immunomodulatory effects include T-cell activation, interferon-gamma production, and increased IL-2 receptor and HLA-DR expression.
Ivermectin
Antihelminthic Agent
Uses: Onchoceriasis, Lymphatic filariasis, strongyloidiasis, scabies, cutaneous larva migrans
Potentiates both glutamate-gated chloride channels in nematode cell membranes and release of GABA from presynaptic terminals -> hyperpolarization of neuromuscular cells and pharyngeal paralysis.
Does not cross BBB but does increase CNS toxicity
Albendazole, Mebendazole
Antihelminthic Agent
Uses: Nematode infection, cysticercosis, echinococcosis
Inhibits tubulin polymerization by binding to beta-tubulin -> degenerative changed in integumental and intestinal cells of helminths.
Praziquantel
Antihelminthic Agent
Uses: Schistosomiasis, tapeworm infections, liver fluke infection
Increases parasite membrane permeability to calcium -> contraction and paralysis of worms
Diethylcarbamazine
Antihelminthic Agent
Uses: filariasis
Stimulates innate immune system, inhibit microtubule polymerization , and inhibit arachidonic acid metabolism.
Excreted by kidneys - consider dose adjustment in pts with decreased kidney function.
