Metz.antiprotozoa

• Antiprotozoal drugs are used to treat diseases caused by protozoans, including malaria, amebiasis, toxoplasmosis, pneumocystosis, trypanosomiasis, and leishmaniasis
• Antiprotozoal drugs


  • Antimalarial agents
  • Drugs for amebiasis
  • Drugs used for other parasites
• Antimalarial agents


  • Chloroquine
  • Artemisinins
  • Mefloquine
  • Primaquine
  • Quinine
  • Antifolates
  • Others
• Chloroquine


  A 4-aminoquinoline derivative that accumulates in the food vacuole of plasmodia and prevents polymerization of the hemoglobin breakdown product heme into hemozoin
• Chloroquine


  • Rapidly absorbed when given orally, widely distributed to tissues, and has an extremely large volume of distribution
  • Excreted largely unchanged in the urine
• Artemisinins


  Metabolized in the food vacuole of the parasite, forming toxic free radicals. Active against P falciparum, including multidrug-resistant strains
• Quinine


  Complexes with double-stranded DNA to prevent strand separation, resulting in block of DNA replication and transcription to RNA
• Mefloquine


  A synthetic 4-quinoline derivative with an unknown mechanism of action
• Primaquine


  A synthetic 8-aminoquinoline that forms quinoline-quinone metabolites, which are electron-transferring redox compounds that act as cellular oxidants
• Antifolate drugs


  • Pyrimethamine
  • Proguanil
  • Sulfadoxine
  • Dapsone
• Antifolate drugs


  • Sulfonamides act as antimetabolites of p-aminobenzoic acid (PABA) and block folic acid synthesis in certain protozoans
  • Pyrimethamine and cycloguanil are selective inhibitors of protozoan dihydrofolate reductases
• Other antimalarial drugs


  • Doxycycline
  • Amodiaquine
  • Atovaquone
  • Halofantrine
• Doxycycline


  A tetracycline that is chemoprophylactic (taken daily) for travelers to geographical areas with multidrug-resistant P falciparum
• Amodiaquine


  Widely used to treat malaria in many countries because of its low cost and, in some geographical areas, effectiveness against chloroquine-resistant strains of P falciparum
• Atovaquone


  A quinine derivative that appears to disrupt mitochondrial electron transport in protozoa
• Halofantrine


  Active against erythrocytic (but not other) stages of all 4 human malaria species, including chloroquine-resistant falciparum
• Drugs for the prevention of malaria in travelers

  • Chloroquine (weekly)
  • Mefloquine (weekly)
  • Doxycycline (daily)
  • Malarone (atovaquone plus proguanil, daily)
  • Primaquine (daily for 14 days)
• Drugs for amebiasis


  • Tissue amebicides (chloroquine, emetines, metronidazole, tinidazole)
  • Luminal amebicides (diloxanide furoate, iodoquinol, paromomycin)
• Tissue amebicides


  Act on organisms in the bowel wall and the liver
• Luminal amebicides


  Act only in the lumen of the bowel
• Diloxanide furoate


  Commonly used as the sole agent for the treatment of asymptomatic amebiasis and is also useful in mild intestinal disease when used with other drugs
• Emetines (emetine and dehydroemetine)

  Inhibit protein synthesis by blocking ribosomal movement along messenger RNA, used parenterally as backup drugs for treatment of severe intestinal or hepatic amebiasis together with a luminal agent in hospitalized patients
• Iodoquinol


  A halogenated hydroxyquinoline, an orally active luminal amebicide used as an alternative to diloxanide for mild-to-severe intestinal infections
• Metronidazole and tinidazole


  Effective orally and distributed widely to tissues, used as the drug of choice in severe intestinal wall disease and in hepatic abscess and other extraintestinal amebic disease, used with a luminal amebicide
• Drugs used in the treatment of amebiasis

  • Diloxanide furoate
  • Iodoquinol
  • Paromomycin
  • Metronidazole
  • Tinidazole
  • Emetine
  • Dehydroemetine
• Paromomycin


  An aminoglycoside antibiotic used as a luminal amebicide, may be superior to diloxanide in asymptomatic infection
• Nitazoxanide


  Has activity against various protozoans (including Entamoeba) and helminths, currently approved in the United States for treatment of gastrointestinal infections caused by G lamblia and Cryptosporidium parvum
• TMP-SMZ


  The first choice in prophylaxis and treatment of human pneumocystis pneumonia (PCP), also prophylactic against toxoplasmosis and infections caused by Isospora belli
• Pentamidine


  Mechanism of action is unknown but may involve inhibition of glycolysis or interference with nucleic acid metabolism of protozoans and fungi, used in primary and secondary prophylaxis of P jirovecii pneumonia and in the treatment of active pneumocystosis in the HIV-infected patient
• Pyrimethamine and sulfonamides


  Combination has synergistic activity against Toxoplasma gondii through the sequential blockade of 2 steps in folic acid synthesis, used for prophylaxis against and treatment of toxoplasmosis
• Atovaquone


  Inhibits mitochondrial electron transport and probably folate metabolism, approved for use in mild to moderate pneumocystis pneumonia
• Alternative drug regimens for the treatment of pneumocystis pneumonia

  • Trimethoprim plus dapsone
  • Primaquine plus clindamycin
  • Trimetrexate plus leucovorin
• Pentamidine


  Commonly used in the hemolymphatic stages of disease caused by Trypanosoma gambiense and T rhodesiense
• Melarsoprol


  An organic arsenical that inhibits enzyme sulfhydryl groups, the drug of choice in African sleeping sickness as it enters the CNS
• Nifurtimox


  A nitrofurazone derivative that inhibits the parasite-unique enzyme trypanothione reductase, the drug of choice in American trypanosomiasis and an alternative agent in African forms of the disease
• Suramin


  A polyanionic compound, a drug of choice for the early hemolymphatic stages of African trypanosomiasis (before CNS involvement)
• Eflornithine


  A suicide substrate of ornithine decarboxylase, effective in some forms of African trypanosomiasis, available for both oral and intravenous use and penetrates into the CNS
• Nifurtimox


  A drug that inhibits the parasite-unique enzyme trypanothione reductase, used in American trypanosomiasis, African forms of the disease, and mucocutaneous leishmaniasis
• Nifurtimox


  • Causes significant toxicity, including allergies, gastrointestinal irritation, and CNS effects
• Suramin


  A polyanionic compound that is a drug of choice for the early hemolymphatic stages of African trypanosomiasis (before CNS involvement), and an alternative to ivermectin in the treatment of onchocerciasis