Antimicrobials

Antiparasitics and Antivirals

Antimicrobials for Protozoan Infections

Antiprotozoan drugs include those that affect protein synthesis, are metabolites, and inhibit DNA synthesis in the organism.

Protozoans are a diverse group of single-celled organisms that inhabit most moist environments apart from the frigid poles of the planet. They are eukaryotic cells and move through the use of flagella, or "false feet" called pseudopods. Protozoans lack cells walls, and most reproduce using asexual reproduction. Some species are able to reproduce sexually, exchanging genetic material to form gametes that will fuse to become a zygote. A few protozoan species are known to be pathogenic to humans and animals. Most protozoan infections occur when the host consumes water containing live protozoans. Some pathogenic species are able to penetrate the skin, but most have to be consumed orally. Trichomoniasis is a sexually-transmitted disease caused by a protozoan parasite called Trichomonas vaginalis that is passed through unprotected sexual contact and usually produces few symptoms. Symptoms that do occur include painful itching, burning, and redness of the genital area. Treatment for trichomoniasis includes use of oral metronidazole medication.

Like many antimicrobials that affect bacteria, protozoan antimicrobials also inhibit protein synthesis, serve as antimetabolites, or inhibit DNA synthesis. The antiprotozoan drugs that inhibit protein synthesis are called lincosamides, which can also be effective against some gram-positive and gram-negative bacteria. These drugs bind to the 50S subunit of the ribosome and prevent the elongation of the protein. Lincosamides drugs are given orally.

Antiprotozoan drugs called antimetabolites, such as chloroquine, atovaquone, furazolidone, and nifurtimox, work to disrupt various parts of the protozoan metabolism. These drugs can interfere with electron transport, inactivate certain enzymes, and prevent glucose uptake. Chloroquine is an antimetabolite that is derived from the wormwood plant and blocks metabolic pathways of the parasite. It is especially effective against the genus Plasmodium, the type of protozoan that causes malaria. Furazolidone blocks carbohydrate metabolism and the initiation of translation during protein synthesis. Nifurtimox is a drug that also shuts down electron transport and is particularly effective against Trypanosoma cruzi, the protozoan that causes Chagas disease, which uses a tick bite as the vector.

Malaria Drug Uptake

As the mature malaria parasite grows within a red blood cell, there are several membrane barriers that need to be crossed by chloroquine, an antimetabolite that shuts down metabolic pathways of the parasite and limits access to the food vacuole, which is the site where hemoglobin degrades. This causes the protozoan parasite that causes malaria to become nonfunctional.

Antimicrobials for Helminth Infections

Antimicrobials against helminths work by inhibiting glucose uptake, preventing oxidative phosphorylation of ATP, and inhibiting nucleic synthesis.

Helminths are eukaryotic, multicellular, parasitic worms that can be seen with the naked eye. The three main groupings of helminths include the cestodes, the trematodes, and the nematodes. All these groups have species that infect mammalian hosts when the helminth eggs are consumed. Many times, the life cycles of these worms involve intermediate hosts, meaning the eggs have to pass through the bodies of other animals before the larvae are able to settle into their final hosts. Parasitic worms can have separate sexes or may be hermaphroditic, with both genders in the same animal. Infection by helminths can commonly occurs through consumption of infected food or water. However, some nematodes are able to penetrate the skin of the host.

Antihelminth drugs work to either disrupt the metabolism of the worm or inhibit nucleic acid synthesis. A drug called benzimidazole is known to inhibit microtubule formation (an essential step of cell division) and prevent glucose uptake by the worms. Without glucose, the worms are unable to perform cellular respiration to produce energy. This drug has also shown to be effective in protozoans. Niclosamide is a drug that prevents the production of ATP in the helminth's mitochondria. Cestodes are particularly affected by this. Other drugs, such as niridazole and oltipraz, have been shown to shut down DNA synthesis in Schistosoma, the worm that causes schistosomiasis and cercarial dermatitis, also known as “swimmer’s itch” in humans. It causes a raised, itchy patch on the skin’s surface. These drugs can bind to the helminth's DNA and prevent it from being copied. They can also reduce the supply of nucleotides available for DNA synthesis.

Tapeworm Life Cycle

Like most helminths (flatworms), the life cycle of the tapeworm involves the ingestion of the eggs and the use of an intermediate host for the developing larvae before the final host is infected.

Antimicrobials for Viral Infections

Antiviral drugs include those that inhibit nucleic acid synthesis, prevent attachment to the host cell, and prevent the uncoating of the viral coat.

Although they are not considered living organisms, viruses are affected by similar types of antimicrobial agents as bacteria and protozoans. The type of drugs used attack the metabolic pathways of the viruses, usually inhibiting nucleic acid synthesis. The drugs acyclovir and adenosine arabinoside inhibit the phosphorylation by kinase enzymes, which prevents the synthesis of RNA and DNA. These are effective in (1) viruses that code for kinase enzymes, (2) the herpesvirus, and (3) HIV, the virus that causes AIDS.

Other types of drugs, called attachment antagonists, prevent the attachment of the virus to the receptor proteins on the outside of the host cell. If the virus cannot attach, it cannot inject its genetic material into the host cell to be replicated. A drug called arildone blocks the attachment of the viruses to the cell membrane and is useful toward treating picornaviruses (such as polio and that which causes the common cold). Neuraminidase inhibitors are also attachment antagonists that work specifically to prevent the influenza virus from attaching to and infecting host cells.

A third type of antiviral drug is called a viral uncoating drug. These drugs, such as amantadine and rimantadine, neutralize the acids within the viruses that are necessary for the uncoating of the virus when it goes to inject its genetic material into the host cell. These drugs are used to prevent influenza A.