Chloroquine

Quinine

Quinidine

Mefloquine

Artemisinin

Artesunate

Dihydroartemisinin

Malaria, all species

Retinopathy, prolonged QTinterval, methemoglobinemia, amnesia, death (supratherapeutic doses), pruitus, muscle weakness, worsening of psoriasis and porphyria

Visual field changes

-In parasite's food vacuole, where it binds to ferriprotoporphyrin IX (heme) and inhibits its polymerization.

-Most strains of P. falciparum have developed resistance to this drug.

-Kills only erythrocytic stage of slasmodial infections.

-Used therapeutically and prophylactically

Malaria, especially P. falciparum

Cinchonism (tinnitus, deafness, headaches, nausea, vomiting, visual disturbances), prolonged QT interval, disseminated intravascular coagulation, thrombocytopenia, hepatotoxicity, hemolytic uremic syndrome, interstital nephritis, rash, hypoglycemia, GI disturbance, headache

Chloroquine-resistant malaria

Seizure, neuropsychiatric symtoms (vivid dreams, insomnia, depression, hallucinations, psychosis), cardiac conduction abnormalities (bradycardia, prolonged QT interval, arrhythmia), GI disturbance, dizziness.

Depression, generalized anxiety disorder, psychosis, schizophrenia, convulsions

-Appears to disrupt polymerization of heme to hemozoin inside intraerythrocytic malarial parasites.

-Used therapeutically and prophylactically.

Malaria, all species

Hemolytic anemia, bradycardia, potential neurotoxic effects

heypersensitivity

-Form carbon-centered free radicals that alkylate heme

-First line therapy for uncomplicated and complicated malaria in combination with a 2nd antimalarial agent

-Not used prophylactically

-Oral artemether-lumefantrine is commercially available in the US for uncomplicated malaria

-IV artesunate is available for treatment of complicated P. falciparum malaria

Primaquine

Atovaquone

P. vivax, P. ovale

Hemolytic anemia, leukopenia, methemoglobinemia, GI distress

Glucose-6-phosphate dehydrogenase (G6PD), Preggers, concomitant meds that cause bone marrow suppression, Rheumatoid arthritis, Lupis

-Used to eradicate hypnozoites of P. vivax and P. ovale; sometimes used as primary prophylaxis against all malarial plasmodia

-Kills both liver and erythrocyte-stage malarial parasites

P. falciparum, toxoplasmosis, babesiosis

GI distress, headache, elevated liver enzymes

Hypersensitivity

-Inhibits the interaction between reduced ubiquinone and the cytochrome bc1 complex

-Used in combination with proguanil or doxycycline

Doxycycline

Tetracycline

Clindamycin

Malaria, all species

Photosensitivity, GI disturbance, esophageal ulceration, tooth discoloration in children, bulging fontanelle in neonates, vaginal candidiasis (doxycycline and tetracycline), C. difficile colitis (clindamycin)

Hypersensitivity, last half of pregnancy, childhood up to 8 y/o

-In combination with quinine, doxycycline or tetracycline is used for the treatment of chloroquine-resistant P. falciparum

-Clindamycin is used in combination with quinine when the use of doxycycline or tetracycline is contraindicated

Sulfadoxine-pyrimethamine

Sulfalene-pyrimethamine

Proguanil

P. falciparum

Stevens-Johnson syndrome, toxic epidermal necrolysis, megaloblastic anemia, leukopenia, thrombocytopenia, nephrotoxicity, GI distress, urticaria

Blood dyscrasias, Infants <2, preggers or breastfeeding, Severe hepatic 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

-Effective against blood schizont stages of P. falciparum, but not against gametocytes

-Sulfadoxine-pyrimethamine can be administered as a single dose, but worldwide resistance to this combination has markedly restricted its utility

Malaria, all species

Pancytopenia, thrombocytopenia, granulocytopenia, oral ulcerations, GI distress, pruritus, headache

Prophylaxis of P. falciparum malaria in patients with severe renal impairment

-Pyrimidine derivative that inhibits plasmodial dihydrofolate reductase

-Primarily active against the hepatic, pre-erythrocytic forms of P. falciparum and P. vivax

-In combination with chloroquine, used for prophylaxis in area where chloroquine resistance is not widespread

-Also used in combination with atovaquone for treatment and prevention of malaria

Anaerobic bacteria, amebiasis, giardiasis, trichomoniasis

leukopenia, thrombocytopenia, ototoxicity, disulfiram-like effect with alcohol, GI disturbance, headache, neuropathy, metallic taste, vaginitis

Hypersensitivity, first trimester of pregnancy, alcohol

-Metronidazole is activated by enzymes in parasites and anaerobic bacteria to form reduced cytotoxic compounds that damage microbial proteins, membranes, and DNA

-Active against E. histolytica trophozoites in tissues, but much less active against intraluminal ameba

-Individuals w/ invasive amebiasis are typically treated first w/ metronidazole and then with a 2nd agent such as iodoquinol or paromomycin

-Tinidazole is a second-generation nitroimidazole related to metronidazole; compared to metronidazole, it is better tolerated and requires a shorter duration of treatment

Giardiasis, Cryptosporidiosis

GI upset, headache

Hypersensitivity

-Structurally related to metronidazole

-Inhibits the pyruvate-ferredoxin oxidoreductase (PFOR) enzyme that converts pyruvate to acetyl CoA in protozoa and anaerobic bacteria

-Mechanism of action against helminths unclear

African trypanosomiasis, Pneumocystis carinii (jiroveci) pneumonia

Paancreatitis, nephrotoxicity, cardiac arrhythmia, hypotension, hypoglycemia, leukopenia, thrombocytopenia, rash, liver enzyme abnormalities, bronchospasm, dizziness

hypersensitivity

-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

-Commonly used as a second-line treatment for individuals with Pneumocystis carinii (jiroveci) pneumonia

Early-stage African trypanosomiasis

Pruritus, paresthesias, vomiting, nausea

Hypersensitivity

-Inhibits RNA polymerase and glycerol phosphate dehydrogenase

Late-stage African trypanosomiasis

Reactive encephalopathy, death, fever, phlebitis, neuropathy

Hypersensitivity

-First-line drug for late-stage African trypanosomiasis, in which the disease involves the central nervous system

-Melarsoprol inhibits trypanosomal pyruvate kinase, thereby inhibiting glycolysis and decreasing ATP production; melarsoprol also inhibits adenine and adenosine uptake by trypanosomal transporters

-Treatment can be associated with 4-6% death rate

-Concomitant administration of corticosteroids lessens the likelihood of reactive encephalopathy

-Concomitant administration of thiamine lessens the likelihood of polyneuropathy

West African trypanosomiasis (IV), Hair removal (topical)

Myelosuppression, thrombocytopenia, seizure, ototoxicity

Hypersensitivity

-Active against early- and late-stage West African trypanosomiasis (T.b. gambiense), but not effective against East African trypanosomiasis (T.b. rhodesiense)

-Selective and irreversible inhibitor of ornithine decarboxylase; T.b. gambiense organisms may be susceptible because of their slow turnover of ornithine decarboxylase

-In the US topical formulation is used for hair removal

New World trypanosomiasis (Chagas' disease)

Pancytopenia, neuropathy, convulsions, vomiting, anorexia, memory loss, sleep disorders

hypersensitivity

-Generates toxic intracellular oxygen radicals in the parasite; mammalian cells are protected by the activity of antioxidant enzymes such as catalase, glutathione peroxidase, and superoxide dismutase

Leishmaniasis

Myelosuppression, chemical pancreatitis, prolonged QT interval, kidney dysfunction, rash

Hypersensitivity

-Contain pentavalent antimony and act by an unknown mechanism; postulated to inhibit the glycolytic pathway and fatty acid oxidation

Visceral Leeishmaniasis (oral), Cutaneous lymphomas and skin metastases from breast cancer (topical)

Leukocytosis, thrombocytosis, GI upset, pruritus, rash

Breastfeeding, concurrent radiation therapy of affected skin, large deep metastases, Pregnancy, small or well-defined areas where radiation or surgery would be successful

-A synthetic ether phospholipid analogue similar to natural phospholipids in cell membranes

-Has antineoplastic, immunomodulatory, and antiprotozoal activity

-May inhibit enzyme systems associated with plasma membranes (such as protein kinase C) and phosphatidylcholine biosynthesis

-May also inhibit platelet activating factor-induced responses and inositol phosphate formation

-Immunomodulatory effects include T-cell activation, interferon-gamma production, and increased interleukin-2 receptor and HLA-DR expression

Onchocerciasis, Lymphatic filariasis, strongyloidiasis, scabies, cutaneous larva migrans

seizure, inflammatory or allergic responses to dying microfilariae ("Mazzotti-type reaction"), including itching, fever, dizziness, headache

Hypersensitivity

-Potentiates both glutamate-gated chloride channels in nematode cell membranes and release of GABA from pre-synaptic terminals --> hyperpolarization of neuromuscular cells and pharyngeal paralysis

-Does not kill adult filarial worms and therefore cannot cure human hosts of O. volvulus infection

-Does not cross the BBB; however, the drug has increased CNS toxicity (headaches, ataxia, coma) when the BBB is hyperpermeable (as in meningitis)

-Resistance has been found in livestock parasites but not in humans; in livestock parasities, the P-glycoprotein may be involved.

Nematode infections, Cysticercosis, Echinococcosis

Agranulocytosis, leukopenia, pancytopenia, thrombocytopenia, hepatotoxicity, acute renal failure, GI disturbance, headache

Hypersensitivity

-Inhibit tubulin polymerization by binding to beta-tubulin --> degenerative changes in integumental and intestinal cells of helminths

-Thiabendazole causes significant nausea, vomiting, and anorexia at therapeutic does and is rarely used

-Mebendazole and albendazole are better tolerated; albendazole has the highest oral bioavailability of the three drugs

-Dose reduction is required for patients with renal insufficiency

Schistosomiasis, Tapeworm infections, Liver fluke infections

Headache, GI disturbance

Hypersensitivity

-Increases parasite membrane permeability to calcium

--> contraction of paralysis of worms

Filariasis

"Mazzotti-type reactions" in individuals with heavy microfilarial burdens, anorexia, headache, nausea

Hypersensitivity

-Mechanism of action unknown; postulated to stimulate innate immune system, inhibit microtubule polymerization, and inhibit arachidonic acid metabolism

-Kills adult filarial worms and is considered a curative agent

-Excreted by the kidneys; consider dose adjustment in individuals with decreased kidney function

Pinworm, roundworm, and hookworm infections

GI disturbance, dizziness

Hypersensitivity

-Causes constant release of acetylcholine --> persistent activation of parasite nicotinic acetylcholine receptors --> tonic paralysis

-Largely replaced by more effective and better tolerated agents

Roundworm infection

GI disturbance, pruritus

Hypersensitivity to piperazine

-GABA agonist --> flaccid paralysis rarely used