Mechanism of Action

The benzimidazole and probenzimidazole drugs are believed to inhibit energy metabolism in susceptible parasites leading to energy exchange breakdown and inhibition of glucose uptake. The drugs also bind to tubulin molecules, which binding inhibits microtubule formation and cell death of susceptible parasites through disruption of cell division.

Dose and Toxicity

If a labeled product containing fenbendazole or febantel is available, the label should be followed for each respective parasite. In general, fenbendazole at the dosage of 50 mg/kg, PO, daily for 3 days, is considered safe and effective against most of the target helminths of both dogs and cats (see Tables 37-1 and 37-2). In the United States, febantel is labeled only for oral administration in dogs. However, the drug has been administered safely to cats in several studies at dosages as high as 56.5 mg/kg (adult cats).^11,14 Side effects at the recommended dosages in dogs and cats are rare, and if side effects occur, generally salivation or vomiting, they are usually mild and self-limiting.

Clinical Application

Fenbendazole and febantel are prescribed frequently for the target helminths as discussed (see Tables 37-1 and 37-2). However, neither compound is effective for the treatment of Dipylidium caninum or Echinococcus spp. infections. Febantel is combined with praziquantel (see “Isoquinolones” section), which effectively treats the other tapeworms and pyrantel (see “Tetrahydropyridimines” section), which increases its activity against hookworms and roundworms (Drontal Plus, Bayer Animal Health). Benzimidazoles also treat Trichuris vulpis infections, which is an advantage over some of the drugs in other classes with anthelmintic activity.

Fenbendazole or febantel are also commonly prescribed to dogs or cats with small bowel diarrhea for potential activity against Giardia spp. (see Chapter 57).^14–17 Fenbendazole is one of the anthelmintics that is believed to have activity against the trematodes that can be associated with gastrointestinal disease (Alaria spp., Nanophyetus salmincola, Heterobilharzia americana, Platynosomum fastosum).¹⁸ However, optimal protocols have not yet been established and fenbendazole is not labeled for this use.

Mechanism of Action

The emodepside mechanism of action is considered unique to the drugs with anthelmintic activity. The drug binds to the latrophilin receptor presynaptically, which activates a complex signal transmission cascade that eventually results in the release of inhibitory neuropeptides into the synaptic gap. The resulting ion influx that occurs postsynaptically results in the inhibition of pharyngeal pump function that leads to paralysis and death of susceptible nematodes.

Dose and Toxicity

Based on the label in the United States, the emodepside-containing topical solution should be applied to cats older than 8 weeks of age and greater than 1 kg of body weight. The drug has been applied to small numbers of pregnant queens and 4-week-old kittens in a research study without apparent side effects.¹⁹ Adverse effects associated with administration of the topical solution to 606 cats in a controlled, double-masked field safety study reported by Bayer Animal Health were infrequent, mild, and self-limited. The reactions reported were licking/excessive grooming in 18 cats (3.0%), scratching treatment site in 15 cats (2.5%), salivation in 10 cats (1.7%), lethargy in 10 cats (1.7%), alopecia in eight cats (1.3%), agitation/nervousness in seven cats (1.2%), vomiting in six cats (1.0%), diarrhea in three cats (0.5%), eye irritation in three cats (0.5%), respiratory irritation in one cat (0.2%), and shaking/tremors in one cat (0.2%).^21–23 Salivation, vomiting, and mild neurologic effects induced by administering the topical solution orally to cats were self-limited. Side effects induced by administration of the oral preparation to dogs have also been minimal.^21–23

Clinical Application

In addition to the label indications, administration of emodepside to a small number of pregnant queens that were experimentally infected with Toxocara cati apparently blocked lactogenic transmission to the kittens.¹⁹ Combining emodepside with praziquantel expands the spectrum of activity to include cestodes and, potentially, trematodes (see “Isoquinolones” section).²³ Emodepside also has effects against helminths of other body systems like feline lungworm.²⁴

Mechanism of Action

The exact mechanisms of action of the isoquinolones are unknown but may relate to inhibition of organism attachment. At low concentrations in vitro, praziquantel appears to impair the function of the cestode suckers and stimulates parasite motility. At higher concentrations in vitro, praziquantel increases the contraction of the worm’s strobila, which can be irreversible at very high concentrations. Isoquinolone administration may cause damage to the integument of susceptible cestodes and trematodes, which may impart increased vulnerability to digestion by the host.