Multidrug resistance (MDR1)
Multidrug resistance is disease represented as hypersensitivity for the certain antiparasitic and several other drugs that predisposes animals to a potentially fatal neurotoxicosis. Disease is caused by degeneration of P-glycoprotein, a protein normally expressed on brain capillary endothelial cells that functions as part of the blood-brain barrier to pump drugs out of the CNS. That way the blood-brain barrier limits the passage of drugs into the NS. Dogs with the gene deletion have increased brain concentrations of drugs including ivermectin, moxidectin, loperamide, and corticosteroids.
Dogs homozygous for the mutation do not express a functional P-glycoprotein and show increased sensitivity to many drugs. Regarding some of these drugs, brain penetration is highly increased, and the dogs develop severe neurotoxicosis, even when the drugs are administered at a normal therapeutic dosage, as in the case of ivermectin and doramectin. Genetic testing allows us to detect the mutation, but it is suggested that demonstration of only one mutation in the canine MDR1 gene cannot completely ensure security from adverse effects of the substrate drugs of P- glycoprotein.
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