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Antiparasitic Drugs for Integumentary Disease in Animals

By

Michael Shipstone

, BVSc, FACVSc, DACVD, University of Queensland

Last full review/revision Apr 2022 | Content last modified Jun 2022

Skin disease caused by ectoparasites is common in large animals. The most common equine parasitic dermatoses are chorioptic mange, pediculosis, habronemiasis, and onchocerciasis. In small animals, parasitic dermatoses are relatively common and may be due to a direct effect of the parasite itself (helminths, fleas, ticks, or mites) or the parasite may act as an intermediate host or vector for bacterial or rickettsial disease.

Isoxazolines for Integumentary Disease in Animals

Isoxazolines are a relatively new chemical class first launched as veterinary products in 2013 and are not naturally produced but rather manufactured. They have a broad spectrum of insecticidal and acaricidal activity. They are noncompetitive GABA receptor antagonists, bind to chloride channels in nerve and muscle cells, blocking signal transmission, and cause hyperexcitation, resulting in uncontrolled activity in the CNS and death of the target. The selective toxicity of isoxazolines between insects, acarines, and mammals is due to the differential sensitivity of the GABA receptors in the respective species.

As of 2022, there are four members of the group that are registered for veterinary use in dogs and cats: afoxolaner, fluralaner, sarolaner, and lotilaner. The registered target species of each active ingredient varies depending on country and include the following: fleas Fleas in Dogs and Cats Ctenocephalides felis (cat flea) on a severely flea-infested and anemic cat. Larva of Ctenocephalides spp (larvae are 1–5 mm in length, with hairs projecting laterally from each... read more Fleas in Dogs and Cats (Ctenocephalides spp), American dog ticks Dermacentor spp Of the 35 currently recognized Dermacentor spp, 19 inhabit temperate zones and 13 are found exclusively in the palearctic region. Among the tropical species, D nitens is of major... read more <i >Dermacentor</i> spp (Dermacentor variabilis), lone star ticks Amblyomma spp More than half of the approximately 135 known Amblyomma species are endemic to the New World. Amblyomma ticks are large, three-host parasites. They have eyes and long, robust mouthparts... read more <i >Amblyomma</i> spp (Amblyomma americanum), black-legged ticks Ixodes spp Ixodes spp, the largest genus of the family Ixodidae, contains approximately 245 species and is highly specialized both structurally and biologically. So far as is known, all Ixodes... read more <i >Ixodes</i> spp (Ixodes scapularis), paralysis ticks Ixodes spp Ixodes spp, the largest genus of the family Ixodidae, contains approximately 245 species and is highly specialized both structurally and biologically. So far as is known, all Ixodes... read more <i >Ixodes</i> spp (Ixodes holocyclus), brown dog ticks Rhipicephalus spp Approximately 60 of the 84 described rhipicephalid species are found in sub-Saharan Africa. The other rhipicephalid species have their origins in Eurasia and northern Africa, with R sanguineus... read more (Rhipicephalus sanguineus), bush ticks Haemaphysalis spp Few of the currently recognized 167 species of Haemaphysalis parasitize livestock, but those that do are economically important in Eurasia, Africa, Australia, and New Zealand. Some haemaphysaline... read more (Haemaphysalis longicornis), demodectic mange mites Canine Demodicosis: Sarcoptes scabiei. Sarcoptes scabiei var canis infestation is a highly contagious disease of dogs found worldwide. The mites are fairly host specific, but animals (including... read more Canine Demodicosis: (Demodex spp, sarcoptic mange mites Sarcoptic Mange (Canine Scabies): Sarcoptes scabiei. Sarcoptes scabiei var canis infestation is a highly contagious disease of dogs found worldwide. The mites are fairly host specific, but animals (including... read more Sarcoptic Mange (Canine Scabies): (Sarcoptes scabiei), and ear mites Otodectic Mange: Sarcoptes scabiei. Sarcoptes scabiei var canis infestation is a highly contagious disease of dogs found worldwide. The mites are fairly host specific, but animals (including... read more Otodectic Mange: (Otodectes cynotis) infestations.

This group of compounds is highly efficacious against Demodex spp and has become the treatment of choice for demodicosis in dogs and cats.

Ivermectin for Integumentary Disease in Animals

Ivermectin is an avermectin and a fermentation product of Streptomyces avermitilis (also see Macrocyclic Lactones Macrocyclic Lactones The macrocyclic lactones (avermectins and milbemycins) are products or chemical derivatives of soil microorganisms belonging to the genus Streptomyces. The avermectins in commercial use... read more ). It acts as a GABA agonist, causing paralysis in susceptible arthropods and nematodes. It is used in small animals for treatment of Sarcoptes scabiei, Otodectes cynotis, Cheyletiella blakei, C yasguri, and Demodex canis; in cattle for psoroptic mange, lice, and Hypoderma larvae; in horses for equine filarial dermatitis from Onchocerca cervicalis; and in swine for Sarcoptes scabiei.

In small animals, all use for skin conditions is in an extralabel fashion in the US. For Demodex, the dosage is 0.3–0.6 mg/kg, PO, every 24 hours, until two negative skin scrapings 1 month apart. For Sarcoptes, Otodectes, and Cheyletiella, the dosage is 0.3 mg/kg, PO, repeated in 2 weeks. In cattle, 0.2 mg/kg is administered as a single subcutaneous injection for Psoroptes and lice. In horses, ivermectin (0.2 mg/kg, PO, repeated as necessary as part of a parasite management program) kills microfilariae but not adult Onchocerca cervicalis, so relapse may be noted within 2 months after treatment. In swine, the dosage is 0.3 mg/kg, SC, repeated in 2 weeks, or 0.1–0.2 mg/kg, in feed, for 7 days.

In mammals, GABA is found only in the CNS and does not readily cross the blood-brain barrier. At least 10 times the normal dose of ivermectin is needed for toxic reactions. Ataxia, CNS depression, and visual impairment develop in horses administered 2 mg/kg, PO. In cattle, 4 mg/kg, by drench, or 8 mg/kg, SC, leads to listlessness and ataxia; 30 mg/kg induces ataxia in swine.

Some dog breeds (Collies, Shetland Sheepdogs, Old English Sheepdogs, Australian Collies, and their crosses) have an abnormality in the blood-brain barrier associated with a mutation of the multiple drug resistance gene, MDR1, that allows increased ivermectin into the CNS and results in toxicity. Dogs that are homozygous for the mutation produce a severely truncated P-glycoprotein (<10% of the normal amino acid sequence) and will develop ivermectin toxicosis at the dosages used to treat demodicosis. The critical point at which transient, nonfatal clinical signs (mydriasis, ataxia, and tremors) are evident seems to be 120–150 mcg/kg. At higher dosages, collapse, coma, and respiratory collapse may develop. Dogs that are heterozygous for the MDR1 gene can also react, although less severely, and similar idiosyncratic reactions may develop in any breed, so a gradually increasing dose (daily progression of 50, 100, 150, 200, then 300 mcg/kg) should be administered to identify susceptible patients. Administration should be stopped if any adverse effects occur.

Milbemycin Oxime for Integumentary Disease in Animals

Milbemycin is derived from fermentation products of Streptomyces hygroscopicus and, like ivermectin, acts as a GABA agonist, although it has a wider spectrum of activity against intestinal parasites. It has been used in an extralabel manner in dogs to treat nasal mites, scabies, and generalized demodicosis. No adverse effects have been reported in ivermectin-sensitive breeds. In dogs, the dosage for nasal mites and scabies is 1–2 mg/kg, PO, every 7 days, for 3–5 treatments, and for Demodex is 1–2 mg/kg, PO, every 24 hours until two negative skin scrapes or hair plucks.

Moxidectin for Integumentary Disease in Animals

Moxidectin belongs to the milbemycin class of compounds. It is registered for heartworm control (Dirofilaria immitis) but has also been used in an extralabel manner for treatment of Otodectes and demodicosis in dogs. In cattle, it is used to treat lice (Linognathus vituli, Solenopotes capillatus, and Bovicola bovis), mites (Psoroptes and Chorioptes bovis), ticks (Boophilus microplus), and fly warbles and grubs (Hypoderma bovis and Hypoderma lineatum). In sheep, it is used for Psorobia ovis infestation. The dosage in dogs is 0.2–0.4 mg/kg, PO, every 24 hours until two negative skin scrapings, and in cattle and sheep is 0.2 mg/kg, topically, once.

Selamectin for Integumentary Disease in Animals

This semisynthetic macrocyclic lactone is applied topically but acts systemically. It is effective against Ctenocephalides spp (both adults and larvae), Sarcoptes scabiei, Otodectes cynotis, and Dermacentor variabilis. The dose in dogs and cats is 6 mg/kg, applied topically, every 30 days as needed.

Lufenuron for Integumentary Disease in Animals

Lufenuron is an insect growth regulator that inhibits synthesis of chitin, a critical component of insect exoskeletons. It is taken up by adult fleas while feeding. Although it has no effect on adult fleas, it prevents development of the intermediate stages of the flea life cycle (ie, eggs, larvae, and pupae). It is effective against Ctenocephalides spp in dogs and cats at a dosage of 10 mg/kg, PO, every 30 days as needed. Chitin is also a component in the fungal cell wall of dermatophytes. An initial study showed efficacy of lufenuron in treating small animal dermatophytosis; however, additional studies have failed to show efficacy.

Nitenpyram for Integumentary Disease in Animals

Nitenpyram inhibits the nicotinic acetylcholine receptor. It is used to treat Ctenocephalides spp in dogs and cats at a dosage of 1 mg/kg, PO, every 24 hours as needed to control adult fleas. Nitenpyram has a short half-life and kills fleas on the animal within 30 minutes of administration. It is toxic to fleas for only 24–48 hours and is normally used in combination with an insect growth regulator to provide continuous flea control.

Spinosad for Integumentary Disease in Animals

Spinosad stimulates the nicotinic acetylcholine receptor, which causes activation of motor neurons and results in involuntary muscle contractions and tremors, leading to paralysis and death of the insect. It is used to treat Ctenophalides spp in dogs at a dosage of 31–70 mg/kg, PO, every 30 days as needed and in cats at a dosage of 50–90 mg/kg, PO, every 30 days as needed. It may trigger severe clinical signs of ivermectin toxicosis if administered concurrently with extralabel, high-dose ivermectin.

Indoxacarb for Integumentary Disease in Animals

Indoxacarb blocks sodium channels in the insect to cause paralysis and death. It is effective against Ctenophalides spp, both adults and larvae, and is applied as a spot-on, topically, once a month.

Cythioate for Integumentary Disease in Animals

Cythioate is an organophosphate that kills via anticholinesterase activity. It is indicated for Ctenocephalides spp infestations at a dosage of 3 mg/kg, PO, twice weekly (dogs) or 1.5 mg/kg, PO, twice weekly (cats). Effective blood concentrations are maintained for <12 hours, but serum cholinesterase activity may be decreased for >1 month after dosing.

Sodium Stibogluconate for Integumentary Disease in Animals

Sodium stibogluconate is used for treatment of cutaneous leishmaniasis Leishmaniosis in Dogs The leishmaniases are spectral diseases caused by protozoan parasites of the genus Leishmania. Key signs range from localized cutaneous lesions to lymphadenopathy and renal failure for... read more Leishmaniosis in Dogs , either as a sole treatment or in combination with allopurinol, paromomycin, or pentamidine. The exact mode of action is unknown; however, it is believed to interfere with energy metabolism in Leishmania amastigotes. Dosage in dogs is 30–50 mg/kg, IV or SC, every 24 hours for 3–4 weeks. If adverse effects occur (musculoskeletal pain, increase in liver transaminase activity, pancreatitis, myocardial injury, hemolytic anemia, leukopenia, or renal dysfunction), the dose may be administered every other day for longer periods. Note that IV administration should be over 5 minutes to minimize cardiotoxicity.

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