Antiparasitic Drugs



Antiparasitic Drugs





Overview


Endoparasitic infections are extremely common in many parts of the world, particularly in areas where the climate is warm and moist, the sanitation is poor, and insects and other vectors of disease are prevalent. In fact, billions of people in tropical and subtropical regions are infected with protozoa (single-cell organisms that dwell in the lumen, tissue, or blood) and helminths (worms, including nematodes, trematodes, and cestodes). Factors such as immigration, an increase in the number of international travelers, and an increase in the number of individuals with acquired immunodeficiency syndrome (AIDS) who are therefore at greater risk for opportunistic infections have all increased the probability that physicians will see endoparasitic infections that were formerly rarely found in their usual patient population.


Since 1960 the introduction of new drugs has enabled remarkable advances in the chemotherapy of some endoparasitic infections. Albendazole and mebendazole have significantly improved the treatment of several intestinal nematode infections, whereas praziquantel has revolutionized the treatment of trematode and cestode infections. At the same time, metronidazole and tinidazole have provided more effective and less-toxic drugs for the treatment of amebiasis, giardiasis, and trichomoniasis. The sites and mechanisms of action of selected antiparasitic drugs are depicted in Figure 44-1.



Unlike endoparasitic infections, ectoparasitic infestations are caused by organisms that live on the skin or hair shafts of patients. The most common examples are the lice and mites that cause pediculosis and scabies, respectively.


Table 44-1 provides information about the causes and treatment of numerous protozoan infections, helminthic infections, and ectoparasitic infestations. The antiparasitic agents that are commonly used or represent pharmacologic advances are discussed in this chapter. In some cases an antibacterial or antifungal agent (e.g., tetracycline or amphotericin B) is listed as either a preferred or an alternative drug; these agents are discussed in earlier chapters. A detailed discussion of other agents listed in the table is beyond the scope of this chapter.



TABLE 44-1


Causes and Treatment of Parasitic Infections and Infestations


















































































































































































































































CONDITION COMMON PATHOGENS PRIMARY DRUGS ALTERNATIVE DRUGS
Intestinal Protozoan Infections
Amebiasis, symptomatic with diarrhea, dysentery, or hepatic abscess Entamoeba histolytica Metronidazole or tinidazole followed by paromomycin or iodoquinol  
Amebiasis, asymptomatic cyst passer E. histolytica Paromomycin or iodoquinol Diloxanide
Balantidiasis Balantidium coli Tetracycline Metronidazole
Cryptosporidiosis Cryptosporidium parvum Nitazoxanide Antidiarrheal medication
Dientamoeba infection Dientamoeba fragilis Iodoquinol Tetracycline, metronidazole, or paromomycin
Giardiasis Giardia intestinalis Tinidazole or nitazoxanide Paromomycin or metronidazole
Microsporidiosis Encephalitozoon and Enterocytozoon species Albendazole Fumagillin
Extraintestinal Protozoan Infections
Amebic meningoencephalitis Naegleria fowleri Amphotericin B, azithromycin or both  
Babesiosis Babesia microti Atovaquone + azithromycin Clindamycin + quinine
Leishmaniasis Leishmania species Miltefosine Amphotericin B, antimony drug, fluconazole (cutaneous infections)
Malaria Plasmodium vivax or Plasmodium ovale Primaquine + chloroquine; primaquine + artesunate Primaquine + quinine and doxycycline
  Chloroquine-sensitive Plasmodium falciparum Chloroquine Artesunate; quinine + doxycycline; mefloquine
  Chloroquine-resistant P. falciparum, prophylaxis Atovaquone + proguanil; mosquito nets and repellants Doxycycline or mefloquine
  Chloroquine-resistant P. falciparum, treatment Artesunate + doxycycline or other drug; artemether + lumefantrine Quinine + (doxycycline or clindamycin or mefloquine)
Toxoplasmosis Toxoplasma gondii Pyrimethamine + sulfadiazine + folinic acid; spiramycin Trimethoprim + sulfamethoxazole; atovaquone
Trichomoniasis Trichomonas vaginalis Metronidazole or tinidazole  
Trypanosomiasis (African sleeping sickness) Trypanosoma brucei Pentamidine (early disease); melarsoprol or eflornithine (late CNS disease) Suramin
Trypanosomiasis, American (Chagas disease) Trypanosoma cruzi Nifurtimox Benznidazole
Intestinal Nematode Infections
Ascariasis Ascaris lumbricoides Albendazole or mebendazole Ivermectin; nitazoxanide
Capillariasis Capillaria philippinensis Mebendazole Albendazole
Pinworm infection Enterobius vermicularis Albendazole or mebendazole Pyrantel pamoate
Hookworm infection Ancylostoma duodenale and Necator americanus Albendazole or mebendazole Pyrantel pamoate
Strongyloidiasis Strongyloides stercoralis Ivermectin Albendazole
Whipworm infection Trichuris trichiura Albendazole Mebendazole or ivermectin
Extraintestinal Nematode Infections
Cutaneous larva migrans Ancylostoma braziliense Albendazole Ivermectin
Guinea worm Dracunculus medinensis Surgical removal  
Filariasis, lymphatic Wuchereria bancrofti; Brugia malayi and Brugia timori Doxycycline 6-8 wk, then add diethylcarbamazine Albendazole or ivermectin
Filariasis, cutaneous Loa loa Diethylcarbamazine Albendazole
River blindness Onchocerca volvulus Doxycycline followed by ivermectin ± prednisone Suramin
Trichinosis Trichinella spiralis Albendazole + prednisone Mebendazole + prednisone
Trematode Infections
Schistosomiasis Schistosoma species Praziquantel Oxamniquine for Schistosoma mansoni
Chinese liver fluke Clonorchis sinensis Praziquantel Albendazole
Sheep liver fluke Fasciola hepatica Triclabendazole or nitazoxanide Bithionol
Lung fluke Paragonimus westermani Praziquantel Bithionol
Cestode Infections      
Beef tapeworm Taenia saginata Praziquantel Niclosamide
Pork tapeworm Taenia solium Praziquantel Niclosamide
Dog tapeworm Dipylidium caninum Praziquantel Niclosamide
Dwarf tapeworm Hymenolepis nana Praziquantel  
Fish tapeworm Diphyllobothrium latum Praziquantel Niclosamide
Cysticercosis Larval T. solium Albendazole or praziquantel for CNS disease + dexamethasone  
Echinococcosis (hydatid disease) Echinococcus granulosus Percutaneous aspiration + albendazole  
Ectoparasite Infestations
Head lice, crabs Pediculus humanus, Phthirus pubis Permethrin, spinosad (head lice) Malathion, ivermectin
Scabies (mites) Sarcoptes scabiei Permethrin Ivermectin


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CNS, Central nervous system.



Drugs for Infections Caused by Lumen- and Tissue-Dwelling Protozoa


Amebiasis, balantidiasis, cryptosporidiosis, giardiasis, and trichomoniasis are examples of infections caused by protozoan parasites that dwell in the lumen and tissues of their human hosts. Among the agents used to treat these infections are metronidazole, tinidazole, iodoquinol, and paromomycin (see Table 44-1).



Metronidazole


Drug Properties




Spectrum and Mechanisms.

Metronidazole is active against several anaerobic protozoa that commonly cause infection. These include Entamoeba histolytica (the agent of amebiasis); Giardia intestinalis (Giardia lamblia, giardiasis); Trichomonas vaginalis (trichomoniasis); and Balantidium coli (balantidiasis). Metronidazole is also active against anaerobic bacteria, including Bacteroides fragilis, Helicobacter pylori, and Clostridium difficile.


A number of anaerobic organisms express pyruvate-ferredoxin oxidoreductase, an enzyme not found in mammalian cells, which is involved in energy production, carbon recycling, and other metabolic functions. In susceptible anaerobic protozoa, this enzyme transfers electrons to the nitro group of metronidazole to form free nitro radicals that attack DNA and proteins and thereby produce a cytotoxic effect.



Indications.

Metronidazole, the drug of choice for amebiasis, giardiasis, and trichomoniasis, is also used as an alternative drug in the treatment of balantidiasis.


Patients with amebiasis can have intestinal infection, with or without dysentery, hepatic abscesses, or other extraintestinal manifestations of disease. Metronidazole acts primarily as a tissue amebicide and is usually given in combination with a luminal amebicide (e.g., iodoquinol) to eradicate intestinal amebas.


Giardiasis causes abdominal discomfort and diarrhea in persons infected with the cyst form of Giardia. In the western United States, Giardia cysts are sometimes present in contaminated streams and ponds and are ingested by campers. The administration of metronidazole for 5 days usually cures the infection.


Trichomoniasis is a sexually transmitted disease that produces vaginitis in women but is usually asymptomatic in men. To prevent reinfection, it is important to treat patients and their sexual partners. Treatment can consist either of a single large dose of metronidazole or of smaller doses taken over a 7-day period.


Metronidazole is also used in the management of several disorders that are not caused by protozoa. For example, it is sometimes used in the treatment of patients with dracunculiasis (guinea worm infection). This infection is caused by Dracunculus medinensis, a nematode found in India, Pakistan, and parts of Africa. Although metronidazole is not curative, it reduces inflammation and facilitates manual removal of the worm. Metronidazole is considered the drug of choice for enterocolitis caused by Clostridium difficile, and it is occasionally used to treat infections caused by other anaerobic bacteria. Metronidazole is available in gel or cream form for the topical treatment of rosacea (acne rosacea), a skin condition characterized by persistent erythema of the middle third of the face and other areas of the body.



Adverse Effects and Interactions.

Metronidazole is usually well tolerated, but it causes considerable gastrointestinal discomfort in some persons. Other adverse effects include nausea, vomiting, a metallic taste, and transient leukopenia or thrombocytopenia. To reduce the gastrointestinal side effects, patients should take metronidazole with food.


Metronidazole increases the anticoagulant effect of warfarin, so the dosage of warfarin should be adjusted as necessary. Metronidazole also causes a disulfiram-like reaction with ethanol, so patients should avoid drinking alcohol while they are undergoing treatment.


Metronidazole has been shown to be mutagenic in bacteria and mammalian cell cultures. Although retrospective studies of women who took the drug during pregnancy failed to reveal an increased incidence of birth defects or cancer, it appears prudent to avoid prescribing the drug to women during their first trimester of pregnancy whenever possible.

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Jul 23, 2016 | Posted by in PHARMACY | Comments Off on Antiparasitic Drugs
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