Antiparasitic drug types
Antiparasitic drugs are essential medications designed to combat infections caused by parasites, which are organisms that depend on a host for survival. These parasites can be classified into three main types: helminths (worms), protozoa (unicellular organisms), and ectoparasites (external parasites like lice). Anthelmintics target helminths and can be further categorized into vermifuges, which paralyze worms, and vermicides, which kill them. Common anthelmintics include drugs like mebendazole, which disrupts the worms' ability to take up glucose.
Antiprotozoal drugs, such as quinine for malaria and metronidazole for amoebic infections, work through various mechanisms, impacting processes like protein synthesis and DNA structure. Ectoparasiticides are used to eliminate external parasites and include compounds like lindane, while endectocides, such as ivermectin, target both internal and external parasites.
Natural products like quinine, derived from the cinchona tree, have historical significance in treating parasitic infections, though their efficacy often requires scientific validation. Parasitic infections are particularly prevalent in regions with inadequate sanitation, affecting billions globally, especially in developing nations. The rise of resistance to antiparasitic drugs poses an increasing challenge in managing these infections, underscoring the need for ongoing research and effective treatment strategies.
Antiparasitic drug types
Definition
Antiparasitic drugs are drugs used to treat infections by parasites, organisms that live at the expense of another organism, or host. Parasites include helminths (worms), protozoa, and ectoparasites.
Anthelmintics
Helminths are parasites that are frequently found in the digestive tracts of humans and other mammals. Other sites of infestation include blood, liver, the lungs, and the skin, and can be dictated by the particular life cycle of the helminth. Helminths include the nematodes (roundworms), cestodes (flatworms), and trematodes (flukes).
The ultimate goal of an anthelmintic drug is to eliminate the worm infestation from the host. Broadly, anthelmintics can be classified as vermifuges, which stun the worm, and vermicides, which kill the worm. Once worms are killed or incapacitated, they are eliminated by the host’s digestive and immune systems.
Anthelmintic drugs include piperazines, tetrahydropyrimidines, imidazothiozoles, benzimidazoles, salicylanilides, nitroaryls, tetrahydroquinolines, isoquinolines, and organometallics. The effectiveness of these drugs varies from parasite to parasite. Mebendazole, one of the benzimidazoles, inhibits the formation of worm microtubules and depletes the worm’s glucose. Mechanisms of action vary from drug to drug.
Efforts have also been made to develop anthelmintic vaccines. These attempts have focused primarily on formulations of helminth antigens, which would sensitize the immune systems of humans and animals against the organism. Initial vaccine efforts have focused on the hookworm.
Antiprotozoals
Protozoa are unicellular eukaryotes. Of the six protozoan phyla, Sarcomastigophora and Apicomplexa include the most important species that cause human disease. Notable Apicomplexa parasites in humans include Plasmodium falciparum, which causes malaria, and Toxoplasma gondii, which causes toxoplasmosis. Other protozoan parasites include Giardia intestinalis, Cryptosporidium species, Trypanosoma species, and various amebas.
Antiprotozoal drugs include quinolines, nitroheterocycles, antifolates, bisamidines, haloacetamides, and organometallics. Quinine, an antimalarial drug, inhibits nucleic acid and protein syntheses, and glycolysis, but the exact mechanism of this inhibition is not completely understood. Metronidazole, an antiamebal, interacts with deoxyribonucleic acid (DNA), causing a loss of helical DNA structure and strand breakage.
Ectoparasiticides and Endectocides
Ectoparasiticides, broadly defined, are substances that kill external parasites, the vectors that carry them, and the vectors that carry internal parasites to their hosts. Ectoparasiticides include scabicides, insecticides, and insect repellents, and comprise a more diverse collection of compounds because of their more varied modes of action. Common examples are lindane, which is used to treat lice and scabies infestations, and insect repellents such as NN-diethyl metatoluamide (DEET).
Endectocides are compounds that possess antiparasitic qualities against both interior (endoparasites) and exterior (ectoparasites) parasites. One example of an endectocide is ivermectin, one of the avermectinclass, which can be used against intestinal threadworms, lice, and scabies. Avermectins bind to glutamate-gated chloride ion channels in invertebrate nerve and muscle cells, which results in an increase in permeability of the cell membrane to chloride ions. This change in permeability leads to hyperpolarization of the cell, resulting in paralysis and death of the parasite. Other mechanisms of action may vary. According to a 2023 article in Clinical Microbiology and Infection, during the COVID-19 pandemic in the early 2020s, some people began taking ivermectin in order to treat the virus. However, experts advised that such treatments, which were most commonly carried out without the supervision of medical professionals, were both unsuccessful at treating a virus and potentially harmful.
Antiparasitic Natural Products and History
A limited number of studies have been conducted outside the scope of the pharmaceutical industry in the use of natural products to eradicate parasitic infestations. These products include kalanji, myrrh, onion, oregano, papaya, and wormwood.
One of the first natural products to be successfully used against a parasite was the bark of the cinchona tree, which contains quinine. Quinine has been used against Plasmodium, the parasite that causes malaria. It should be noted that these products often require a process to formulate them into the preparation given in these studies, and it should not be inferred that consuming the source product necessarily will give the same effect. Many of these products also require further testing to validate their use.
Impact
Parasitic infections are common in areas in which sanitation and water cleanliness standards do not achieve a level required to prevent their transmission. In these areas, antiparasitic drugs are often the best defense against infectious agents such as helminths and amebas. In addition to gaining entry to the human body through oral and oral-fecal routes, certain parasites, such as the hookworm, can gain entry through breaks in the skin. Often because of poverty, people do not wear shoes that would protect them against soil-transmitted parasites like the hookworm. Other parasites, such as the pinworm, can be contracted by inhaling aerosolized eggs.
The World Health Organization (WHO) estimated in 2023 that, worldwide, 1.5 billion persons, or 24 percent of the population, were infected with helminths, making it one of the world's most common infections. The bulk of this burden fell on the developing countries, although parasites, such as Trypanosoma and Plasmodium, can be carried to industrialized areas from regions where parasitic infections are endemic. Immunocompromised persons should be monitored for infection more closely, as parasites have been found outside their usual target organs or in greater numbers when the immune system cannot mount its normal defense.
Resistance to antiparasitic drugs has increased. This resistance is now presenting its own challenges to the elimination of parasites. For this reason, scientists are continually working to develop new antiparasitic drugs.
Bibliography
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Barac, Aleksandra, et al. "Inappropriate Use of Ivermectin During the COVID-19 Pandemic." Clinical Microbiology and Infection, vol. 28, no. 7, 23 Mar. 2022, pp. 908-910, doi: 10.1016/j.cmi.2022.03.022. Accessed 4 Feb. 2025.
Cairncross, Sandy, Ralph Muller, and Nevio Zagaria. “Dracunculiasis (Guinea Worm Disease) and the Eradication Initiative.” Clinical Microbiology Reviews 15, no. 2 (2002): 223-246.
Hotez, Peter J., et al. “Helminth Infections: The Great Neglected Tropical Diseases.” Journal of Clinical Investigation 118, no. 4 (2008): 1311-1321.
Roberts, Larry S., and John Janovy, Jr. Gerald D. Schmidt and Larry S. Roberts’ Foundations of Parasitology. 8th ed. Boston: McGraw-Hill, 2009.
Sharma, Satyavan. Approaches to Design and Synthesis of Antiparasitic Drugs. New York: Elsevier Science, 1997.
"Soil-Transmitted Helminth Infections." World Health Organization, 18 Jan. 2023, www.who.int/news-room/fact-sheets/detail/soil-transmitted-helminth-infections. Accessed 3 Feb. 2025.