Tiêu đề 16. CHEMOTHERAPY OF PROTOZOAL INFECTIONS (AMOEBIASIS, GIARDIASIS).pdf ✅

PHARMD GURU Page 1  Protozoal infections are common among people in underdeveloped tropical and subtropical countries, where sanitary conditions, hygienic practices, and control of the vectors of transmission are inadequate.  However, with increased world travel, protozoal diseases, such as malaria, amebiasis, leishmaniasis, trypanosomiasis, trichomoniasis, and giardiasis, are no longer confined to specific geographic locales.  Because they are eukaryotes, the unicellular protozoal cells have metabolic processes closer to those of the human host than to prokaryotic bacterial pathogens.  Therefore, protozoal diseases are less easily treated than bacterial infections, and many of the antiprotozoal drugs cause serious toxic effects in the host, particularly on cells showing high metabolic activity, such as neuronal, renal tubular, intestinal, and bone marrow stem cells.  Most antiprotozoal agents have not proved to be safe for pregnant patients. AMOEBIASIS  Amebiasis (also called amebic dysentery) is an infection of the intestinal tract caused by Entamoeba histolytica.  The disease can be acute or chronic, with patients showing varying degrees of illness, from no symptoms to mild diarrhea to fulminating dysentery.  The diagnosis is established by isolating E. histolytica from fresh feces.  Therapy is aimed not only at the acutely ill patient but also at those who are asymptomatic carriers, because dormant E. histolytica may cause future infections in the carrier and be a potential source of infection for others. LIFE CYCLE OF ENTAMOEBA HISTOLYTICA:  Entamoeba histolytica exists in two forms: cysts that can survive outside the body and labile but invasive trophozoites that do not persist outside the body.  Cysts, ingested through feces-contaminated food or water, pass into the lumen of the intestine, where the trophozoites are liberated. CHEMOTHERAPY OF PROTOZOAL INFECTIONS (AMOEBIASIS, GIARDIASIS)
PHARMD GURU Page 2  The trophozoites multiply, and they either invade and ulcerate the mucosa of the large intestine or simply feed on intestinal bacteria. [Note: One strategy for treating luminal amebiasis is to add antibiotics, such as tetracycline, to the treatment regimen, resulting in a reduction in intestinal flora, the ameba’s major food source.]  The trophozoites within the intestine are slowly carried toward the rectum, where they return to the cyst form and are excreted in feces.  Large numbers of trophozoites within the colon wall can also lead to systemic invasion.  A summary of the life cycle of E. histolytica is presented in Figure 36.2.
PHARMD GURU Page 3 CLASSIFICATION: Classification (According to their Site of Action) 1. Luminal amoebicides: They are poorly absorbed after oral administration, hence attain high concentration in the bowel. They act on trophozoites in the gut lumen and kill them. a) Amides: Diloxanide furoate and nitazoxanide b) 8-Hydroxyquinolines: Iodoquinol, iodochlorhydroxyquin c) Antibiotics: Tetracyclines, paromomycin 2. Tissue amoebicides: They attain high concentration in blood and tissues following oral or parenteral administration. a) Nitroimidazoles: Metronidazole, tinidazole, secnidazole, ornidazole, satranidazole b) Alkaloids: Emetine, dehydroemetine (DHE) c) 4-Aminoquinoline: Chloroquine Among tissue amoebicides, nitroimidazoles and alkaloids are used for intestinal and extraintestinal amoebiasis. Chloroquine is used for extraintestinal amebiasis. 1. LUMINAL AMOEBICIDES: A) AMIDES: DILOXANIDE FUROATE:  Diloxanide furoate is a synthetic compound. The trophozoites in gut lumen which form cysts are killed by diloxanide furoate (luminal amoebicide). It is not effective against tissue trophozoites.  After oral administration, diloxanide furoate in the gut is split into diloxanide and furoic acid. The diloxanide moiety is partly absorbed; the unabsorbed portion in the gut exerts antiamoebic activity.  It is the drug of choice for asymptomatic amoebic carriers. In intestinal and extraintestinal amoebiasis, diloxanide furoate is given along with a tissue amoebicide for complete eradication of the organism (i.e. both trophozoites and cysts).
PHARMD GURU Page 4  Diloxanide furoate is administered in a dose of 500 mg t.d.s. for about 7–10 days. It is well tolerated and rarely causes side effects, such as flatulence, nausea and skin rashes. NITAZOXANIDE:  Nitazoxanide is a luminal amoebicide. It is converted to active metabolite (tizoxanide). It is useful orally in amoebiasis and giardiasis.  Adverse effects are headache and GI disturbances. B) 8-HYDROXYQUINOLINES: Hydroxyquinolines were widely used as luminal amoebicides in the past for amoebiasis. They have been banned in various countries because of their toxicity, subacute myelooptic neuropathy (SMON). C) ANTIBIOTICS: TETRACYCLINES:  They are luminal amoebicides. The unabsorbed portion of older tetracyclines reaches colon and inhibits the bacterial flora, which are required for survival of E. histolytica. PAROMOMYCIN:  Paromomycin, an aminoglycoside, is a luminal amoebicide. It is not absorbed from the GI tract following oral administration. It alters the intestinal flora.  Adverse effects like nausea, vomiting and abdominal pain can occur. Oral paromomycin is safe for use in pregnancy. It is also useful in kala-azar. 2. TISSUE AMOEBICIDES: A) NITROIMIDAZOLES: METRONIDAZOLE: Metronidazole is a nitroimidazole derivative which is highly effective against most anaerobic bacteria and several protozoa, such as E. histolytica, Giardia lamblia and Trichomonas vaginalis. It helps in the extraction of guinea worm (Dracunculus medinensis).