Имидаклоприд инструкция по применению для кошек

Sources

Imidacloprid (1-[(6-chloro-3-pyridinyl)-methyl]-N-nitro-2-imidazolidinimine) is a neonicotinoid of the chloronicotinyl nitroguanidine class.¹⁵ Imidacloprid is used with pyriproxyfen in topical spot-on products to kill all life stages of fleas on dogs and cats and to prevent and control lice infestations on dogs.¹⁶ The manufacturer states that these products should be used with caution in debilitated, aged, pregnant, or nursing animals, and kittens less than 8 weeks of age or puppies less than 7 weeks of age. Imidacloprid is used in combination with permethrin in dog-only spot-on products that control fleas and ticks. Topical formulations of imidacloprid in combination with moxidectin are used on dogs and cats to prevent heartworms as well as control fleas, ear mites, and intestinal nematodes.¹⁷

Toxic Dose

Dermal LD₅₀ of technical imidacloprid for rats is more than 5000 mg/kg.¹⁵ Dogs fed up to 41 mg/kg of imidacloprid for a year developed increased cholesterol levels and increased concentration of cytochrome P450.¹⁸ Kittens exposed topically to 5.2 times the recommended dose of an imidacloprid-moxidectin combination developed mydriasis, salivation, depression, squinting, and poor appetite.¹⁷

Toxicokinetics

According to the technical profile of the spot-on formulation, topically applied imidacloprid spreads rapidly over the skin by translocation.¹¹ The product is not systemically absorbed, but sequesters in hair follicles and glands where it is shed with sebum. Ingested imidacloprid is quickly absorbed from the gastrointestinal tract.^11,13 Within 48 hours, 96% of absorbed imidacloprid is eliminated via urine (70% to 80%) and feces (20% to 30%).¹¹

Mechanism of Toxicity

Imidacloprid blocks nicotinergic pathways, which results in a buildup of acetylcholine at the neuromuscular junction.^7,11 Acetylcholine buildup results in insect hyperactivity, then paralysis, and later death.

Clinical Signs

There is limited published information detailing adverse effects of imidacloprid in dogs or cats; however, clinical effects from the veterinary product are expected to be mild. Because the drug is bitter tasting, oral contact may cause excessive salivation.^7,11 Signs of poisoning from imidacloprid are similar to nicotinic signs, including lethargy, vomiting, diarrhea, hypersalivation, initial tremors, muscle weakness, and ataxia.¹⁵

Animals exposed to oral or topical overdoses of imidacloprid-moxidectin combination products may develop signs consistent with avermectin toxicosis: mydriasis, depression, ataxia, tremors, blindness, and coma (see Chapter 52).⁷

Minimum Database

Assessment of the hydration status and urinary function may be required because the kidneys are the primary sites of elimination of imidacloprid.

Confirmatory Tests

Some laboratories can test for imidacloprid in hair and skin samples. However, these results can only confirm the exposure because toxic levels in tissues have not been determined.

Treatment

There is no specific antidote for imidacloprid; treatment for adverse effects would be symptomatic and supportive. If the exposure is dermal, the treatment includes initial stabilization and bathing with a mild dishwashing detergent. Treatment of ingestion of a topically applied veterinary imidacloprid product should consist of dilution with milk or water.

Hypersensitivity skin reactions could occur with any topical product. In those instances, a bath with a noninsecticidal shampoo and symptomatic care, such as hydrocortisone, antibiotics, or antihistamines, is recommended.

Animals exposed to moxidectin-containing formulations and showing signs consistent with macrocyclic lactone toxicosis (e.g., depression, ataxia, mydriasis, blindness, salivation) should be managed as outlined in Chapter 52, “Ivermectin: Macrolide Antiparasitic Agents.”

Prognosis

Although published reports of adverse effects of imidacloprid are limited, in most situations, animals are expected to recover within 24 to 72 hours with veterinary care.

Differential Diagnoses

Differential diagnoses for reactions to oral exposures (drooling, gagging, etc.) include corrosive oral injury, exposure to insoluble calcium oxalate-containing plants, and nontoxicant-related nausea.

Lungworm

A. abstrusus has worldwide distribution.⁴² Adult A. abstrusus lungworms live in the respiratory bronchioles and alveolar ducts of cats. After mating, the females produce eggs that hatch in this same location. The first stage larvae (L1) then ascend the bronchial tree to the pharynx, from where they are swallowed and subsequently excreted in the feces and into the environment. L1s are then ingested by slugs and snails that act as intermediate hosts, with rodents, frogs, lizards, snakes, or birds acting as paratenic hosts. Cats become infected by ingesting a mollusk or a paratenic host (or both).²⁷²

Most infections are subclinical^96,244; however, heavy infections can result in clinical signs as a result of damage to the lung parenchyma induced by eggs and larvae. Severe disease can be fatal. Severe clinical disease was reproduced experimentally after kittens were infected with 800 L3 larvae; coughing developed 6 weeks after exposure.⁹⁷ A. abstrusus infection can mimic allergic respiratory disease because radiographs often demonstrate a bronchointerstitial pattern (although an alveolar pattern predominates during the period of heaviest larval shedding at 5 to 15 weeks post infection) and BAL fluids comprise predominantly eosinophils; further, cats can show an initial positive response to administration of corticosteroids and bronchodilators.^88,271

Diagnosis depends on recognition of the organism in feces, BAL fluid, or pleural fluid.^140,272 In one study standard fecal examination recognized A. abstrusus in only 21.7% of infected cats.¹²⁸ Using the Baermann technique to examine feces is considered the most sensitive method for larval detection; however, sensitivity is less than 90%.^140,285 A PCR assay for A. abstrusus has recently been validated for use on Baermann sediment, feces, and pharyngeal swabs. This shows great promise to aid in diagnosis, with a reported specificity of 100% and sensitivity of 96.6%.²⁷²

Many parasiticides have proved to be effective in treating cats with A. abstrusus infection. Fenbendazole has been used at 20 mg/kg orally every 24 hours for 5 days or 50 mg/kg orally every 24 hours for 15 days.^16,88,98 Ivermectin (0.4 mg/kg subcutaneously, repeated 2 weeks later) has been reported to be effective in some reported cases.^27,131 Abamectin (0.3 mg/kg subcutaneously, repeated 2 weeks later) was effective in the treatment of one cat.⁷⁸ A single topical application of imidacloprid/moxidectin reduced larval counts by 100% in one study,^269a and topical application of emodopside/praziquental reduced larval counts by 99.4% in another.^272a Two applications of selamectin (6 mg/kg, topical) were effective in the treatment of only one of three cats.⁸⁸

Eucoleus aerophilus (formerly Capillaria aerophilus) has been recognized worldwide.^15,197,270 The life cycle is considered direct. There is, however, some speculation that earthworms may serve as a paratenic or intermediate host. Infection may not result in clinical signs; alternatively, a chronic cough and weight loss may develop. Infection is rarely fatal.⁴² Definitive diagnosis is by detection of eggs on sugar and zinc sulfate solution fecal flotation²⁷⁰; eggs may also be detected in BAL samples.¹⁵ Radiographs typically show a diffuse interstitial lung pattern, and BAL cytology shows an eosinophilic inflammatory response.⁴² Abamectin (0.3 mg/kg subcutaneously, repeated 2 weeks later) has been reported as effective treatment in one cat.¹⁵ Other anthelmintics, such as ivermectin or milbemycin oxime, may also be effective in cats.⁴²

Lung Fluke

P. kellicotti is a trematode that can infect the lungs of cats and dogs in the Eastern United States, mainly in areas surrounding the Mississippi River. Other species of Paragonimus can affect cats across eastern Asia and Central and South America. The disease in man is endemic in southeast Asia and portions of central Africa.²¹⁴ Adult flukes live within cysts inside the lung parenchyma and are about 6 mm long. Eggs are deposited into the lung tissue, where they are coughed up, swallowed, and then passed in the feces. If the eggs enter fresh water, they begin to develop and produce a ciliated miracidium, which hatches and seeks out a young snail host. After asexual multiplication in the snail, the cercarial stage is produced, which penetrates the shell of a crayfish and encysts in an area near the heart of the crustacean. Within the crayfish the cercaria forms a cyst wall and becomes a metacercaria. When the crayfish is ingested by a cat (or dog), the excised metacercariae penetrate the intestinal tract and enter the peritoneal cavity, within which they migrate for 7 to 10 days before entering the pleural cavity through the diaphragm. The lungs are entered approximately 2 weeks after infection.²⁵⁹ Dogs and cats typically become infected by eating metacercariae in crayfish, but rats can serve as paratenic hosts and transmammary or transplacental transmission is also thought to be possible.²³ Clinical signs such as occasional coughing are usually mild, although pneumothorax can result from migrating flukes. Early lesions appear radiographically as indistinct nodular densities containing small air cavities and having irregular, sharply defined margins; older cysts are usually air-filled pneumatocysts, but ill-defined interstitial nodular densities may also be seen.^229,280 Successful treatment has been reported with praziquantel (25 mg/kg orally every 8 hours for a total dose of 150 mg/kg) and albendazole (25 mg/kg orally every 12 hours for 11 to 24 days).^23,61,114

Toxoplasma

Toxoplasma gondii may cause self-limiting small bowel diarrhea but typically causes no disease in cats. However, transplacentally or lactationally infected kittens and immune-suppressed older cats can show severe systemic signs.⁶⁰ In a study of 100 cases with histologically confirmed toxoplasmosis, 76.7% of 86 lung tissue samples assessed had organisms present, and in the 36 cats considered to have generalized toxoplasmosis, 26 had predominantly pulmonary lesions.⁵⁹ Retrospective studies of feline LRT infection have found T. gondii in 1 of 20 cats (5%)⁷⁸ and 6 of 245 cases (2.4%).¹⁷ Diagnosis is achieved by recognition of Toxoplasma tachyzoites, which can be found in BAL fluid¹⁴ or FNA of affected lung tissue.^219,235 Diffuse interstitial to alveolar patterns are typically described,^14,219,235 but a bronchial influence is also possible¹⁴ (Figure 30-20). Serology can aid diagnosis.⁶⁰ Recognition of Toxoplasma in an adult cat should instigate investigations to determine a cause of immune suppression, which is often FIV related^50,78 but can be iatrogenic (e.g., due to administration of corticosteroids or cyclosporin).^14,77 Treatment is covered in detail in Chapter 23 but is typically with clindamycin at 12.5 to 25 mg/kg orally every 12 hours for 2 weeks⁶⁰; combination therapy with pyrimethamine at 0.25 to 0.5 mg/kg orally every 12 hours may help the prognosis.¹⁴ Supportive care such as oxygen therapy maintenance of fluid and electrolyte balance is also important. Successful treatment of clinical feline toxoplasmosis has been described infrequently.^14,59,143

Heartworm

Despite prevalence studies demonstrating a worldwide distribution and recognizing heartworm infection in up to 18% of cats tested,* the prevalence rate being approximately 5% to 10% of that found in dogs,^84,150,153 and the prevalence being found similar to that of FIV and FeLV infection,^150,151,158 feline heartworm disease remains underdiagnosed in general practice.^30,195 This is likely because clinical signs vary dramatically from no signs to sudden death and definitive diagnosis can be difficult.^{20,30,153,196}

Heartworm disease is caused by the filarioid nematode Dirofilaria immitis, which is transmitted by mosquitos and for which dogs are the usual definitive host. Therefore a prerequisite for heartworm infection is a climate with adequate temperature and humidity to support a viable mosquito population and allow maturation of larvae within the intermediate host. The sexually dimorphic adult heartworm mate within an infected dog’s pulmonary artery, producing immature forms called microfilariae. Circulating microfilariae are ingested by mosquitoes feeding on infected dogs. Within mosquitoes, microfilariae transform into larval stages. There are five larval stages (L1 to L5); L1 to L3 transformations occur within the mosquito, and L3 is the form that is transmitted from mosquitos to dogs and cats. Maturation from L3 to other larval stages occurs in subcutaneous tissues and peripheral veins of mammalian hosts; immature worms in peripheral veins are carried in the bloodstream to and through the heart, with adult heartworms ultimately residing at the caudal pulmonary arteries.¹

There are significant differences between feline and canine heartworm disease because the parasite is only partially adapted to the cat. The cat is susceptible to heartworm infection but more resistant than the dog. The cat represents a dead-end host because it cannot act as a reservoir for infection. The prepatent period in the cat is 7 to 8 months (1 to 2 months longer than in dogs).¹⁶⁹ In dogs, most juvenile worms mature into adults that can live for 5 to 7 years, whereas in cats most juvenile worms die shortly after arriving in the pulmonary arteries, instigating a severe vascular and parenchymal inflammatory response. Pulmonary lesions may be long lasting. The clinical response in the cat has been termed heartworm-associated respiratory disease (HARD). In a small percentage of cats, a few worms develop to mature adults that can live for 2 to 3 years.¹⁹⁵

Cats with adult heartworms develop pulmonary changes characterized by intimal proliferation, eosinophilic endarteritis, intimal fibrosis, and disruption of the internal elastic lamina. Arterial wall changes can lead to pulmonary hypertension with resultant pulmonary arterial distention.¹⁷³ Damage can be caused by juvenile heartworms without development to the adult stage, resulting in increase in thickness of the pulmonary arterial wall that in turn causes occlusion.^26,56 There have been suggestions that Wolbachia pipientis, a symbiotic gram-negative intracellular bacterium harbored by D. immitis induces further pulmonary pathology.⁵⁷ A strong antibody response against Wolbachia surface protein has been demonstrated in heartworm-infected cats. Further research is required to define the exact relationship between Wolbachia and HARD in cats. Upon death of heartworms, it has been hypothesized that degenerating parasites may cause an acute anaphylactic reaction and thromboembolism, which can result in fulminant pulmonary failure and sudden death of the cat.¹⁵² Even the death of one adult heartworm can be lethal. Adult heartworms are able to suppress pulmonary intravascular macrophage activity and therefore induce little inflammation until they die.

Clinical signs can vary from no clinical signs, reported in 28% to 79% of cases,^7,84 to acute or chronic respiratory tract signs. Sudden death has been reported in 7% to 47% of naturally infected cats with mature adult heartworm infections.^7,68,84,277 Additional signs that may be seen include neurologic signs or vomiting.^7,277

Heartworm antigen testing detects mature female heartworm genital parts, so sensitivity increases when more female worms are present. Because heartworm antigen testing is regarded as highly specific, false-positive results are very rare. One study found 36% sensitivity with only one female heartworm and increasing to 93% sensitivity with seven females present. Cats with only male heartworms test as negative.¹⁷⁷ A more recent study comparing antigen tests detected 79.3% to 86.2% of necropsy confirmed heartworm infections. Most cats with false-negative antigen tests had a single male worm.²⁰ On the basis of this study, it can be assumed that antigen testing will detect at least three quarters of cats infected with adult heartworm. However, as previously noted, clinical signs can result from larval infections that do not progress to adult stage heartworms.

Antibody tests will help determine exposure, but up to 79% cats with exposure do not become symptomatic.⁸⁴ A negative antibody test does not rule out infection. The different antibody tests available vary in sensitivity and specificity, insofar as each brand may detect a different stage of larval development. Also, up to 30% of cats on heartworm prophylaxis may become antibody positive, although they are not at risk for HARD. Combining antigen and antibody testing achieves higher sensitivity than either test alone but may generate more false-positive results.²⁵⁰

Radiographic findings may add to a clinician’s index of suspicion for heartworm disease, but results are inconsistent. Significant enlargement of the central and peripheral caudal lobar pulmonary arteries (greater than 1.6 times the width of the ninth rib) in the ventrodorsal view has been considered a typical radiographic sign of heartworm infection in cats. However, this was recognized in only 53% of cases in one study²³⁷ and only 1 of 11 cats in another.²⁷⁷ The latter study found diffuse or focal bronchointerstitial patterns to be most common, with focal changes supporting a better prognosis.²⁷⁷

Echocardiography, in experienced hands, can also aid diagnosis. Adult heartworms typically appear as two echodense parallel lines within the pulmonary artery, one of its branches, or the right ventricle. One study found heartworms in 17 of 43 cats with echocardiography but, it is important to note, allowed a definitive diagnosis to be made in five cats in which antigen test results were negative; four of these five cats had positive antibody test results.⁵³

There is no definitive treatment for heartworm disease in cats. Most cats with infection are asymptomatic, and it is appropriate to start prophylactic treatment in these cats. Heartworm prophylactic treatments have been demonstrated to be slowly adulticidal in dogs,¹⁶⁸ and there is no reason to assume that this would not also be the case in cats. Ivermectin has the most potent adulticidal activity, milbemycin the least, with selamectin and moxidectin in between.¹⁶⁸ More rapid kill of adult heartworm with arsenical agents such as thiacetarsemide or melarsomine is not recommended. These agents are believed to be less potent in cats and have significant toxicity, and death of heartworms may result in fatal pulmonary embolism.¹⁵³ Successful surgical removal of heartworms has been reported, although there are substantial risks associated with the procedure. In particular, crushing or transecting the adult heartworms can induce a fatal shock reaction. Trauma to the jugular vein during multiple heartworm retrievals may result in transection of the vein.²⁴⁸

In most cases, in addition to heartworm prophylaxis, it is appropriate to manage the clinical signs of infected cats with corticosteroids and bronchodilators. Prednisolone has been used at 2 mg/kg orally every 24 hours and then tapered at remission of clinical signs.⁸⁴ If W. pipientis is demonstrated to be relevant to clinical disease, a 3-week course of doxycycline (5 mg/kg orally every 12 hours) would be appropriate.⁵⁷ Monitoring of heartworm-infected cats with radiographic evidence of disease may include repeat thoracic radiographs at 6- to 12-month intervals. Infected cats can also be monitored with repeat serologic testing. Recovery is indicated by an improvement in radiographic signs and seroconversion of a positive antigen test to negative.

In areas where heartworm is endemic for dogs, all serologic evidence points to the appropriateness of cats (including those confined to indoors) receiving regular prophylactic treatment. There are several macrocytic lactone drugs registered for feline heartworm prophylaxis: ivermectin (Heartguard FX chewables, Merial), milbemycin oxide (Milbemax, Novartis), moxidectin (Advocate/Advantage Multi, Bayer; NB also contains imidacloprid), and selamectin (Revolution or Stronghold, Pfizer).