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Antiprotozoal drugs

The protozoans, unlike bacteria and fungi, do not have a cell wall. They have a nucleus and a cytoplasm that is surrounded by a selectively permeable cell (plasma) membrane. The cytoplasm contains organelles similar to those found in other animal and plant cells (e.g., mitochondria, Golgi apparatus, and endoplasmic reticulum). Thus, most of the antibiotics effective in inhibiting bacteria are not active against protozoans. Amphotericin B, however, reacts with sterols, which are components of both fungal and protozoal membranes. Most of the drugs used in the chemotherapy of diseases caused by the protozoans are derived from plants or are synthetic chemical compounds.

Metronidazole is usually given orally for the treatment of vaginal infections caused by Trichomonas vaginaliis, and it is effective in treating bacterial infections caused by anaerobes. It affects these organisms by causing nicks in, or breakage of, strands of DNA or by preventing DNA replication.

Iodoquinol inhibits several enzymes of protozoans. It is given orally for treating asymptomatic amebiasis and is giveneither by itself or in combination with metronidazole for intestinal and hepatic amebiasis. Balantidium coli and Dientamoeba fragilis infections also are treated with iodoquinol. Emetine, an alkaloid derived from ipecac syrup, is obtained from the roots of Cephaelis ipecacuanha, a plant native to Brazil. It is used along with iodoquinol or chloroquine phosphate as alternative therapy for treatment of severe intestinal and hepatic amebiasis. Emetine is given by injection and can cause serious toxicity. Dehydroemetine is less toxic than emetine and may be used as an alternative drug.

Quinacrine is the drug of choice for giardiasis, an infection of the intestine caused by a flagellated amoeba. Quinacrine inserts itself into DNA, thereby ultimately preventing the synthesis of nucleic acids. It is given orally and can cause yellow staining of skin and sclera and deposition of blue and black pigment in the nail beds.

Trypanosomes are flagellated protozoans that cause a number of diseases. Trupanosoma cruzi, the agent of Chagas' disease, is treated with nifurtimox, a nitrofuran derivative. It is given orally and results in the production of activated forms of oxygen, which are lethal to the parasite. Other forms of trypanosomiasis (African trypanosomiasis, or sleeping sickness) are caused by T. gambiense or T. rhodesiense. When these parasites invade the blood or lymph, the drug of choice is suramin, a nonmetallic dye that affects glucose utilization and hence energy production. Because suramin is not absorbed from the gastrointestinal tract, it is given by intravenous injection. In the late form oftrypanosomiasis, when the parasites have invaded the central nervous system, melarsoprol and tryparsamide areadministered intravenously. They are used because they can penetrate the central nervous system and affect cellular structures and their functions.

Pneumocystis carinii causes pulmonary disease in immunocompromised patients. These infections are treated with trimethoprim-sulfamethoxazole, which inhibits folic acid synthesis in protozoans. An alternative agent for treatment of these diseases is pentamidine, which probably affects the parasite by binding to DNA. Because the drug is not well absorbed from the gastrointestinal tract it is given by the intramuscular route.

Malaria is one of the more serious protozoal infections. Chloroquine phosphate, given orally, is the drug of choice for prophylaxis and treatment. In regions where chloroquine-resistant Plasmodium falciparum is encountered, however, pyrimethamine, in combination with sulfadoxine, is used for prophylaxis. Both drugs interfere with folic acid synthesis and are well tolerated. Quinine sulfate, along with pyrimethamine and sulfadoxine, are used to treat infections caused by chloroquine-resistant P. falciparum.. A high level of quinine in the plasma frequently is associated with cinchonism, a mild adverse reaction associated with such symptoms as a noise in the ears (tinnitus), headache, nausea, abdominal pain, and visual disturbance. Primaquine phosphate is given orally to prevent attacks after a person has left an area where P. vivax and P. ovale are endemic and to prevent relapses with the same organisms.