There are three families of helminths that are primarily responsible for infections in humans.  These include the

nematodes, broadly classified as roundworms including true roundworms (ascarids), whipworms (trichurids), hookworms (Necator and Ancylostoma spp.), threadworms (Strongyloides) and pinworms (Enterobius)

trematodes -- the flukes

cestodes -- tape worms

Mechanism of Action -- These agents inhibit tubulin synthesis thus decreasing glucose transport into the worm (glucose uptake in helminths is mediated by a tubulin-dependent transport mechanism).  Thiabendazole is also known to inhibit  fumarate reductase, thus decreasing the formation of ATP. The worm is deprived of its energy source and is essentially "starved" to death.

Spectrum of Activity -- The benzimidazoles are a broad-spectrum class of agents, effective against numerous helminthic infections.  Albendazole and mebendazole are used primarily in the treatment of ascariasis (rounds), trichuriasis (whips), hooks, pins, and in cysticercosis (the larval stage of pork tapeworm).  They are also effective against threads.  Albendazole is the drug of choice in the treatment of hydatid disease, a relatively uncommon infection by a specific tape worm.  Thiabendazole is the treatment of choice for threadworm infection.  It is also effective in the treatment of "creeping eruption" or larval migrans, the cutaneous migration of larval forms of the worm.

Course of Therapy -- One course of therapy (1 to 3 days in length) is usually effective against most helminthic infections.  Treatment in pinworm infections may have to be repeated in two weeks, to ensure death of worms that were immature during the initial treatment.  Benzimidazole therapy for tapeworm infections and hydatid disease is usually chronic.

Side Effects -- Generally mild and transient including GI upset, headache, dizziness, lassitude, insomnia, and with chronic therapy -- reversible hepatic effects, alopecia, anæmia.

Clinical Aspects --

Albendazole and mebendazole are poorly absorbed on an empty stomach but greatly absorbed when taken with fatty meals.  If the target infection is in tissues, the medication should be taken with such a meal.  If the infection is gastrointestinal, they should be taken on an empty stomach.

Thiabendazole is well absorbed on an empty stomach.  Other differences with thiabendazole include its anti-inflammatory, antipyretic, and immunostimulant effects (all of which may be beneficial in helminthic infections).  It produces similar side effects as the other agents of the class but may also cause tinnitus, bradycardia, hypotension, hyperglycæmia, and CNS effects including convulsions.

Mechanism of Action -- Unknown, bithionol may work may uncoupling oxidative phosphorylation, thus reducing the production of ATP in the helminth.

Spectrum -- Bithionol is the drug of choice in the treatment of sheep liver fluke and the second drug of choice in lung fluke.

Side Effects -- Diarrhœa, abdominal cramps (up to 40% incidence), anorexia, nausea, vomiting, dizziness

Mechanism of Action -- Increases the helminthic cell permeability of calcium, thus increasing calcium influx.  This in turn causes a tetanic paralysis of the musculature and worm death.

Spectrum -- Praziquantel is effective in the treatment of schistosomal trematodes, liver fluke, and lung fluke.  It is NOT effective against sheep liver fluke (Fasciola sp.) or mature tapeworms.

Side Effects -- Headache, dizziness, drowsiness, lassitude, nausea/vomiting/diarrhœa, elevated liver enzymes, low grade fever, rash.  NOTE that the incidence of side effects is less in children that adults.

Contraindications -- The use of praziquantel is contraindicated in ocular cysticercosis because the death of the worm may cause ophthalmic damage and blindness.

Mechanism of Action -- Niclosamide inhibits helminthic oxidative phosphorylation.  An increase in ATPase activity may also contribute to its efficacy.

Spectrum -- Niclosamide is the drug of choice for most tapeworm infections.  Niclosamide is effective in the treatment of beef, pork, and fish tapeworms.  It is NOT effective for hydatid infections or cysticercosis.

Side Effects -- Primarily GI, incidence less than 4%.

Mechanism of Action -- This agent immobilises the worm (presumably through an anti-cholinergic effect at neuromuscular junctions) and decreases the surface structure integrity of the worm, thus making it more susceptible to the host defences and immune responses.

Spectrum -- DCB is the drug of choice for filariasis, a specific nematodal infection.

Side Effects -- Headache, malaise, anorexia, weakness, and less often -- GI effects, damage to eye (similar to praziquantel) and other effects that are due to the death of the worm (fever, malaise, rash, headache, GI effects, cough, and chest, muscle, or joint pain -- NOTE that many of these effects are similar to the drug and ALSO that these effects may be seen with any anthelminthic that results in worm death, rather than worm expulsion).

Mechanism of Action -- Anticholinergic action at the neuromuscular junction, causing helminthic paralysis.  Piperazine is metabolised to a nitrosamine, however this is not thought to contribute to its action nor to increase the risk of cancer in patients.

Spectrum -- An alternative treatment for ascariasis (true roundworm infection) -- if pyrantel or mebendazole are not effective.  Piperazine is an older compound that is little used now except in persistent infections.

Side Effects -- GI, dizziness, headache, may also see somnolence, ataxia, seizures and other motor effects, allergy.

Contraindications -- Piperazine should not be used in patients with epilepsy, renal failure, or hepatic failure.

Clinical Note -- Piperazine usually requires a longer duration of therapy than newer anthelminthics.

Mechanism of Action -- Ivermectin acts as a GABA agonists, causing a flaccid paralysis in the worm.  It also decreases embryogenesis in offspring of the worm.  Ivermectin does not cross the blood brain barrier in humans (therefore little CNS effects).

Spectrum -- Ivermectin is the treatment of choice in onchocerciasis (a nematode infection) -- treatment for this infection requires long term administration either 1 treatment every 3 months for 1 year OR 1 monthly treatment for 3 months EITHER of which is followed by repeat treatments every 12 months for up to ten years.  (One time treatment would cause a remission of the infection, but the larval stages may survive, causing the signs and symptoms of infection to reappear.)

Ivermectin is also effective in the treatment of threadworm infection -- One time treatment is curative in 80% of cases.  It may also be used in other roundworm infections.

Side Effects -- Usually none.

Contraindications -- Ivermectin should not be used in patients with a decrease in blood brain barrier integrity (i.e. meningitis).

Pyrantel/Oxantel

Mechanism of Action -- These agents are depolarising neuromuscular blockers.  The increase acetylcholine release and also inhibit acetylcholinesterase, thus causing ganglionic and myoneural stimulation and paralysis.

Spectrum -- Highly effective against pins, rounds (ascarids), and Trichostrongylus.  They are also effective, though less so, with hooks.  The primary use of pyrantel is the OTC treatment of pinworm infection (which usually comprises a one-dose treatment that may be repeated in two weeks).

Side Effects -- infrequent, transient, and mild -- GI, drowsiness, headache, insomnia, rash, fever.

Mechanism of Action -- Unknown, may be due to ability to decrease DNA binding but also causes a tetanic paralysis of the worm.  The fluke will become paralysed and detach from the mesenteric vessels and taken to the liver where males die.  The females survive and may migrate back to the mesentery but are infertile.

Spectrum -- Only used for Schistosoma mansoni, a fluke (trematode).

Side Effects -- Usually mild but of high incidence -- dizziness, headache, drowsiness -- more rare -- GI, rash, CNS/seizures, liver toxicity.