M. Sc. In Pharm (Pharmacology) Antiamebic drugs Pawitra Pulbutr M. Sc. In Pharm (Pharmacology)

วัตถุประสงค์เชิงพฤติกรรม มีความเข้าใจและอธิบายถึงกลไกการออกฤทธิ์, เภสัชจลนศาสตร์ และอาการไม่พึงประสงค์ของยา Antiamebic มีความเข้าใจและอธิบายถึงการนำไปใช้ประโยชน์ทางคลินิกของยา Antiamebic

Entamoeba histolytica infection .... Protozoa Amebiasis Entamoeba histolytica infection .... Protozoa

Forms of Amebiasis 1. Asymptomatic intestinal infection 2. Mild to moderate intestinal infection 3. Severe intestinal infection (dysentery) 4. Hepatic abscess 5. Ameboma or extrahepatic forms of amebiasis

Antiamebic drugs Kill... trophozoite Tissue Amebicides Active at intestinal wall, liver, other tissues Not effective in lumen Nitroimidazole Metronidazole, Tinidazole, Nimorazole, Ornidazole Emetines Chloroquine...Liver

Antiamebic drugs Luminal amebicides Active in intestinal lumen Dichloroacetamides Diloxanides furoate Halogenated hydroxyquinolines iodoquinol clioquinol Antibiotics … Paromomycin, Tetracyclines, Erythromycin

Metronidazole Tissue amebicides Most effective for invasive amebiasis Expected mechanism... Toxic oxygen products Destroy trophozoite DNA

Metronidazole Clinical uses Drug of choice for intestinal amebiasis extraintestinal amebiasis congenital trichomiasis

Other Nitroimidazole Tinidazole Nimorazole Ornidazole Longer half life Metronidazole = Flagyl® Tinidazole = Fasigyn®

Emetine & Dehydroemetine tissue amebicide Irreversible block of protein synthesis Block ribosome translocation on mRNA Parenterally Accumulate in liver, lung, spleen, kidney

Chloroquine High level in liver use in ... Amebic liver abscess...ONLY

Luminal amebicides Diloxanide furoate direct amebicide…unknown mechanism dissociate in lumen into diloxanide & furoic acid 90% diloxanide absorption Unabsorbed diloxanide....Active luminal amebicide

Iodoquinol iodoquinol = diiodohydroxyquin luminal amebicide Unknown mechanism of action Interfere thyroid function test decrease 131I uptake Alternative to diloxanide furoate

Treatment amebiasis Asymptomatic intestinal infection not necessary in endemic area... Reinfection Luminal amebicide DOC....diloxanide furoate

Tissue amebicide + Luminal amebicide Treatment amebiasis Mild to moderate intestinal infection Severe intestinal infection (dysentery) Hepatic abscess / other extrahepatic infection Tissue amebicide + Luminal amebicide DOC Metronidazole + diloxanide furoate

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