Читать книгу Canine and Feline Epilepsy - Luisa De Risio - Страница 207

The macrocyclic lactones, including avermectins (abamectin, ivermectin, eprinomectin, doramectin and selamectin) and milbemycins (moxidectin, milbemycin and nemadectin), are parasiticides able to kill a wide variety of arthropods and nematodes. Ivermectin is commonly used as heartworm preventative in dogs and cats, as ear miticide in cats, as treatment of sarcoptic and demodectic mange in dogs, and as anthelminthic in ruminants, swine and horses. Intoxication can occur when ivermectin is inadvertently overdosed by the owner or veterinarian or when dogs or cats are exposed to products intended for large animals (including by ingestion of contaminated faeces), which contain a higher concentration of ivermectin than small animal products. In addition, subpopulations of herding type breeds, primarily collies as well as Shetland sheepdogs and Australian shepherds, old English sheepdogs, German shepherds and some mixes of these breeds have a unique sensitivity to macrocyclic lactones and other drugs due to an autosomal recessive mutation in the ATP-binding cassette (ABC) B1 (ABCB1) gene (formerly named multidrug resistance 1 (MDR1) gene). This mutation results in a lack of functional permeability glycoprotein (P-gp) (Nelson et al., 2003; Merola and Eubig, 2012). P-gp is a member of the ATP-binding cassette (ABC) superfamily of transporters and represents an important neuroprotective component of the blood-brain barrier as it limits the entry of macro-cyclic lactones and other xenobiotics into the CNS. The defective P-gp results in accumulation of relatively high concentrations of P-gp-substrate drugs in the CNS, even when relatively low doses of drug are administered.