Isoniazid is an antimetabolite drug used to treat tuberculosis, along with rifampin and streptomycin. It prevents the synthesis of mycolic acid used to make the cell wall of these organisms. Like other drugs against tuberculosis, it can be hepatotoxic but also causes nerve damage and anemia. A new class of drugs is the diarylquinolines, which inhibits ATP synthesis in cases of tuberculosis. It is a risky class of drugs to use because it is hepatotoxic and causes heart arrhythmias. For this reason, it is not used unless there is severe tuberculosis that cannot otherwise be treated effectively.
OTHER ANTIMICROBIAL THERAPIES Other antimicrobial drugs are more difficult to use because fungi, helminths, and protozoans are eukaryotic so selective toxicity is more difficult to manage. Antiviral drugs often damage host human cells because the viruses reproduce intracellularly. Antifungal drugs most often target the cell membrane of fungi because fungi have ergosterol in the cell membrane, which isn’t the case in humans, who use cholesterol. Imidazoles impair ergosterol synthesis, including ketoconazole, miconazole, and clotrimazole, which treat many human fungal infections like yeast infections, athlete’s foot, and ringworm. Related drugs include fluconazole, which can be given intravenously, terbinafine, which targets a different step in ergosterol biosynthesis, and amphotericin B, which creates pores in the fungal cell membrane by binding to ergosterol. Much less commonly used are the echinocandins, which affect fungal cell walls, and nikkomycin Z, which affects chitin synthesis. Griseofulvin interferes with fungal cell division by blocking the mitotic spindle; it is only used topically. Atovaquone is an antimetabolite that mimics coenzyme Q. Antiprotozoal drugs target the differences between protozoans and humans. Atovaquone targets the electron transport chain in protozoal organisms. Proguanil is another antiprotozoal drug that blocks folic acid synthesis. It is used along with atovaquone to treat malaria. Artemisinin is also effective against malaria and tends to build up reactive oxygen species in these organisms. 181
