Other Antimicrobial Therapies

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.

There are other antimetabolite drugs that will treat things like toxoplasmosis. Sulfadiazine blocks folic acid synthesis and can also treat malaria. Pyrimethamine is a related drug that targets a different enzyme in folic acid synthesis.

Nitroimidazoles and quinolones block nucleic acid synthesis in protozoal organisms. Metronidazole is used to treat giardia, trichomonas, and Entamoeba infections. The drug breaks DNA strands, blocking DNA replication. The main adverse effect is an increase in cancer risk in humans. Pentamidine is also a drug that blocks DNA replication, used to treat African sleeping sickness and leishmaniasis. In addition to its effects on DNA replication, it also affects the loading of amino acids onto transfer RNA.

Quinolones are used to treat malaria and are related to quinine. They block the ability of the protozoan to take up amino acids from hemoglobin. It cannot be used long-term because of serious adverse effects. It will also treat amebiasis.

Helminths are hard to treat because these are multicellular eukaryotes. Mebendazole and albendazole can treat these infections by preventing the formation of microtubules. It affects the intestines of the helminth so that glucose cannot be taken up. Ivermectin blocks specific glutamate-gated chloride channels only seen in invertebrates so they die from starvation and paralysis. Several helminthic infections are treated with ivermectin as are infections with bed bugs, lice, and mites.

Other drugs against helminths include Niclosamide, used to treat tapeworm infestations because it is not absorbed by the GI tract. Praziquantel will also treat liver flukes, schistosomiasis, and tapeworm infections. Thioxanthenones are related to quinine and treat schistosomiasis. They block RNA synthesis.

Antiviral drugs are used against viruses. It is hard for scientists to develop specific drugs that are not also toxic to humans. Most of these drugs are nucleoside analogs that block nucleic acid synthesis. Acyclovir mimics guanosine and is used for herpes viral infections. This includes genital herpes, shingles, chickenpox, and Epstein-Barr viral infections. The biggest risk of using this drug is nephrotoxicity. Ribavirin is another guanosine analog, used to treat hepatitis C along with interferon.

Amantadine and rimantadine bind to certain transmembrane proteins so that the influenza virus cannot escape the cell. The biggest problem with this drug is the