Anti-Protozoal

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Antimalarial Blood schizonticide - kill parasite form in erythrocyte. Acute Attacks

MOA - accumulates in food vacuole of plasmodia and prevents polymerization of hemeglobin breakdown product heme (toxic to parasites) into hemozoin.

USE - drug of choice for acute attacks of nonfalciparum and sensitive falciparum malaria and for chemoPROPHYLAXIS, except in regions where PF is resistant.

TOX - GI distress and skin rash at low doses and peripheral neuropathy, skin lesions, auditory and visual impairment, qunidine-like cardiotoxicity at high doses.

RESISTANCE - efflux via P-glycoprotein pump.

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Chloroquine

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Antimalaria Blood schizonticide. Acute Attacks

MOA - Complexes with dsDNA to prevent strand separation, blocking DNA replication/transcription.

USE - in P. Falciparum infections resistant to chloroquine.

TOX - cinchonism (GI distress, headache, vertigo, blurred vision, and tinnitus), disturbances in cardiac conduction, hemolysis in G6PD-deficient patients, Blackwater Fever (intravascular hemolysis). CONTRAINDICATED in pregnancy.

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Quinine - isomer of qunidine (class IA antiarrhythmic)

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Antimalarial with unknown MOA. Acute Attacks.

USE - first-line drug for prophylaxis in all geographical areas with chloroquine resistance.

TOX - GI distress, dizziness, seizures in overdose, arrhythmias.

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Mefloquine

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Antimalaria used in eradication of liver stages (P vivax, P ovale).

MOA - forms quinoline-quinone metabolites, which are electron-transfering redox compounds that act as cellular oxidants. Also limits malaria transmission by acting as a gametocide.

TOX - well tolerated but may cause GI distress, pruritus, headaches, and methemoglobinemia. HEMOLYSIS in G6PD deficient patients. CONTRAINDICATED in pregnancy.

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Primaquine

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Antimalarials used in acute attacks but only in resistant P falciparum. Blood schizonticide.

MOA - Sulfonamides act as antimetabolites of PABA and block folic acid synthesis by inhibiting dihydropteroate synthase while Pyrimethamine and Cycloguanil are selective inhibitors of protozoan DHFR. Sequential Blockade with Pyrimethamine with Sulfadoxine together.

TOX - skin rashes, GI distress, hemolysis, kidney dmage, and drug interactions caused by competition for plasma protein binding sites.

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Antifolate (Pyrimethamine, Proguanil, Sulfadoxine, Dapsone)

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Antimalarial. CHEMOPROPHYLACTIC for travelers to geographical areas with both chloroquine- and mefloquine-resistant P falciparum.

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Doxycycline

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Treatment of malaria in many countries due to its low cost and effectiveness against chloroquine-resistant strains of P falciparum.

HEMO TOX - agranulocytosis and aplastic anemia.

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Amodiaquine

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Antimalarial of unknown mechanism.

Active against erythrocytic stages of all 4 human malaria species.

TOX - QT prolongation and embryotoxicity. Thus, not used for chemoprophylaxis

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Halofantrine

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Antimalarial Blood Schizonticide.

MOA - metabolized in the food vacuoles of the parasite forming toxic free radicals.

Not used in chemoprophylaxis due to short half lives.

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Artesunate and Artemether

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First choice for asymptomatic amebiasis.

MOA - converted in gut to diloxanide freebase form, which is the active amebicide.

TOX - GI symptoms.

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Diloxanide Furoate

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Used as backup drugs for severe intestinal or hepatic amebiasis in hospitalized patients.

MOA - inhibit protein synthesis by blocking ribosomal movement along mRNA.

TOX - GI distress, muscle weakness, CV dysfunction.

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Emetine and Dehydroemetine

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Orally active luminal amebicide used as an alternative drug for mild-to-severe intestinal infections.

TOX - GI. High doses may lead to thyroid enlargement and neurotoxic effects, including peripheral neuropathy and visual dysfunction.

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Iodoquinole

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AMINOGLYCOSIDE antibiotic used as a luminal amebicide.

TOX - GI, headache, dizziness, rashes, and arthralgia.

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Paromomycin

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Used for Pneumocystosis, Toxoplasmosis, hemolymphatic stages of Trypanosomiasis, and kala azar form of Leishmaniasis.

TOX - following pareneteral use, including respiratory stimulation followed by depression, hypotension resulting from peripheral vasodilation, hypoglycemia, anemia, neutropenia, hepatitis, and pancreatitis.

MOA unknown.

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Pentamidine

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FIRST CHOICE in prophylaxis and treatment of pneumocystis pneumonia (P. carinii). Also prophylactic against toxoplasmosis and infections caused by Isospora Belli.

TOX - gi distress, rash, fever, neutropenia, and thrombocytopenia.

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TMP-SMX (trimethoprim-sulfamethoxazole)

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-combination has synergistic activity against Toxoplasma gondii through sequential blockade of 2 steps in folic acid synthesis.

Active against many gram negative bacteria, including Aeromonas, Enterobacter, H influenzae, Klebsiella, Moraxella, Salmonella, Serratia, and Shigella.

TOX - sulfonamide: hypersenstivity, myelotoxicity, kernicterus, and drug interactions caused by competition for plasma protein binding.

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ANTIFOLS: Pyrimethamine and Sulfonamide

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Drug used for Pneumocystosis and Toxoplasmosis

MOA - inhibits mitochondrial electron transport and probably folate metabolism.

TOX - avoid in patients with a history of cardiac conduction defects, psychiatric disorders, or seizures.

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Atovaquone

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First Line Choice for chemoprophylaxis of chloroquine-resistant malaria.

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Malarone (Proguanil w/ Atovaquone)

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Drug of Choice in African sleeping sickness and for Trypanosomiasis.

MOA - inhibits enzyme sulfahydyl groups.

TOX - may cause a reactive encephalopathy that can be fatal.

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Melarsoprol

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Drug of Choice for American Trypanosomiasis.

MOA - inhibits the parasite-unique enzyme trypanothione reductase.

TOX - causes allergies, GI irritation, and CNS effects.

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Nifurtimox

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Drug of Choice for the early hemolymphatic stages of African Trypanosomiasis (T brucei gambiense, T rhodesiense).

- an alternative to Ivermectin in treatment of onchocerciasis.

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Suramin

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Suicide substrate of Ornithine Decarboxylase - effective in some forms of African trypanosomiasis.

Penetrates into the CNS and seizures have occured in overdose.

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Eflornithine

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Drug of Choice for Leishmaniasis (all species).

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Sodium Stibogluconate

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Drug of Choice for mild to severe intestinal infection of amebiasis.

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Metronidazole plus Diloxanide or Iodoquinol

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Regiment of choice for treating amebiasis w/ severe extraintestinal disease and HEPATIC ABSCESS.

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Metronidazole plus Diloanide, followed by Paramomycin