Nematodes, trematodes, and cestodes are three major groups of helminths (worms) that infect humans. Anthelmintic drugs are aimed at metabolic targets that are present in the parasite but either are absent from or have different characteristics than those of the host. Most anthelmintics target eliminating the organisms from the host, as well as controlling spread of infections.
Anthelmintic Drugs: DRUGS FOR THE TREATMENT OF NEMATODES
Focus topic: Anthelmintic Drugs
Nematodes are elongated roundworms that possess a complete digestive system. They cause infections of the intestine as well as the blood and tissues.
Mebendazole [me-BEN-da-zole], a synthetic benzimidazole compound, is a first-line agent for the treatment of infections caused by whipworms (Trichuris trichiura), pinworms (Enterobius vermicularis), hookworms (Necator americanus and Ancylostoma duodenale), and roundworms (Ascaris lumbricoides). Mebendazole acts by inhibiting the assembly of the microtubules in the parasite and also by irreversibly blocking glucose uptake. Affected parasites are expelled in the feces. Adverse effects include abdominal pain and diarrhea. Mebendazole should not be used in pregnant women. [Note: Many anthelmintics should be avoided in pregnancy; however, in mass prevention or treatment programs, certain agents (for example, mebendazole or albendazole) may be used in the second or third trimester.]
B. Pyrantel pamoate
Pyrantel pamoate [pi-RAN-tel PAM-oh-ate] is also effective in the treatment of infections caused by roundworms, pinworms, and hookworms. Pyrantel pamoate is poorly absorbed orally and exerts its effects in the intestinal tract. It acts as a depolarizing, neuromuscular-blocking agent, causing release of acetylcholine and inhibition of cholinesterase, leading to paralysis of the worm. The paralyzed worm releases its hold on the intestinal tract and is expelled. Adverse effects are mild and include nausea, vomiting, and diarrhea.
Thiabendazole [thye-a-BEN-da-zole], a synthetic benzimidazole, is a potent broad-spectrum anthelmintic agent. Current use of thiabendazole is limited to the topical treatment of cutaneous larva migrans (creeping eruption). Because of its toxic effects, it has been largely replaced by other agents for many clinical applications.
Ivermectin [eye-ver-MEK-tin] is the drug of choice for the treatment of cutaneous larva migrans, strongyloidiasis, and onchocerciasis (river blindness) caused by Onchocerca volvulus (kills microfilariae but has no activity against adult worms). [Note: Ivermectin is also useful in the treatment of pediculosis (lice) and scabies.] Ivermectin targets the glutamate-gated chloride channel receptors. Chloride influx is enhanced, and hyperpolarization occurs, resulting in paralysis and death of the worm. The drug is given orally and does not readily cross the blood–brain barrier. Ivermectin should not be used in pregnancy. The killing of the microfilaria in onchocerciasis can result in a dangerous Mazzotti reaction (fever, headache, dizziness, somnolence, and hypotension). The severity of this reaction is related to parasite load. Antihistamines or steroids may be given to ameliorate the symptoms.
Diethylcarbamazine [dye-eth-il-kar-BAM-a-zeen] is the drug of choice for filariasis caused by infection with Wuchereria bancrofti and Brugia malayi. It kills the microfilariae and has activity against adult worms. [Note: In countries where filariasis is endemic, a combination of antifilarial drugs (either diethylcarbamazine and albendazole or ivermectin and albendazole) may be used as preventive chemotherapy.] Diethylcarbamazine is rapidly absorbed following oral administration with meals and is excreted mainly in the urine. Adverse effects may include fever, nausea, vomiting, arthralgia, and headache. [Note: Diethylcarbamazine can accelerate blindness and cause severe Mazzotti reactions in patients with onchocerciasis. It should be avoided in patients with this disorder.]
Anthelmintic Drugs: DRUGS FOR THE TREATMENT OF TREMATODES
Focus topic: Anthelmintic Drugs
The trematodes (flukes) are leaf-shaped flatworms that are generally characterized by the tissues they infect (for example, liver, lung, intestinal, or blood;
Praziquantel [pray-zi-KWON-tel] is an agent of choice for the treatment of all forms of schistosomiasis, other trematode infections, and cestode infections such as taeniasis. Praziquantel is also used off-label in the treatment of cysticercosis (caused by Taenia solium larvae; Permeability of the cell membrane to calcium is increased, causing contracture and paralysis of the parasite. Praziquantel should be taken with food and not chewed due to a bitter taste. It is rapidly absorbed after oral administration and distributes into the cerebrospinal fluid (CSF). The drug is extensively metabolized, and the inactive metabolites are excreted primarily in the urine. Common adverse effects include dizziness, malaise, and headache as well as gastrointestinal upset. Dexamethasone, phenytoin, rifampin, and carbamazepine may increase the metabolism of praziquantel. Cimetidine causes increased praziquantel levels. Praziquantel is contraindicated for the treatment of ocular cysticercosis, because destruction of the organism in the eye may cause irreversible damage.
Anthelmintic Drugs: DRUGS FOR THE TREATMENT OF CESTODES
Focus topic: Anthelmintic Drugs
The cestodes, or “true tapeworms,” typically have a flat, segmented body and attach to the host’s intestine. Like the trematodes, the tapeworms lack a mouth and a digestive tract throughout their life cycle.
Niclosamide [ni-KLOE-sa-mide] (no longer available in the United States) is an alternative to praziquantel for the treatment of taeniasis, diphyllobothriasis, and other cestode infections. It inhibits the mitochondrial phosphorylation of adenosine diphosphate (ADP) in the parasite, making it lethal for the cestode’s scolex and segments but not for the ova. Anaerobic metabolism may also be inhibited. A laxative is administered prior to oral administration to purge the bowel of all dead segments and to enhance digestion and liberation of the ova. Alcohol should be avoided within 1 day of niclosamide use.
Albendazole [al-BEN-da-zole], another benzimidazole, inhibits microtubule synthesis and glucose uptake in nematodes and is effective against most nematodes known. Its primary therapeutic application, however, is in the treatment of cestodal infestations, such as cysticercosis and hydatid disease (caused by larval stage of Echinococcus granulosus). [Note: Albendazole is also very effective in treating microsporidiosis, a fungal infection.] Albendazole is erratically absorbed after oral administration, but absorption is enhanced by a high-fat meal. The drug distributes widely, including the CSF. It undergoes extensive first-pass metabolism, including formation of an active sulfoxide. Albendazole and its metabolites are primarily excreted in the bile. When used in short-course therapy (1 to 3 days) for nematodal infestations, adverse effects are mild and transient and include headache and nausea. Treatment of hydatid disease (3 months) has a risk of hepatotoxicity and, rarely, agranulocytosis or pancytopenia. Medical treatment of neurocysticercosis is associated with inflammatory responses to dying parasites in the CNS, including headache, vomiting, fever, and seizures.[/sociallocker]