Ivermectin and Multi Drug Sensitivity
Ivermectin and multi-drug sensitivity is an autosomal-recessive genetic disease characterized by reactions to various pharmaceuticals.
This disease has been reported in the Australian Shepherd, Whippet, Shetland Sheepdog, Old English Sheepdog, Greater Swiss Mountain Dog, Border Collie, and various rough and smooth Collie breeds and is associated with a defect in the ATP-binding cassette transporter B1 (ABCB1 gene; formerly MDR1 gene) that results in a lack of functional P-glycoprotein, which leads to accumulation of the drugs in the central nervous system and a higher risk of adverse effects when exposed.
This gene encodes a protein, P-glycoprotein that is an integral component of the blood-brain barrier as an efflux pump for xenobiotics crucial in limiting drug uptake into the central nervous system. Dogs with the mutant gene cannot pump some drugs out of the brain as a normal dog would, which may result in abnormal neurologic signs.
This genetic mutations results in a predisposition to allergic reactions to a wide-range of ivermectin-based and other drugs.
Dogs that are homozygous for the deletion mutation display the ivermectin-sensitive phenotype, while those that are homozygous normal or heterozygous do not display increased sensitivity to ivermectin.
Drugs which are commonly reported in MRD-1 affected dogs include:
- Macrocyclic lactones - ivermectin, doramectin, selamectin, milbemycin oxime
- Chemotherapy drugs - vincristine, doxorubicin, prednisolone
- Cardiac glycosides - digoxine, methyldigoxine
- Antiarrhythmics - verapamil, diltiazem, chinidine
- Analgesics - morphine, buprenorphine
- Anti-emetics - metoclopramide, ondansetron, domperidon
- Antibiotics - sparfloxacin, grepafloxacin, erythromycin
- Antihistamines - ebastin
- Tranquillisers - acepromazine
- Other drugs - etoposide, mitoxantrone, paclitaxel, rifampicin
Clinically affected dogs present with acute anorexia, fever, ataxia, seizures and death following application of various drugs, particularly macrocyclic lactones.
A tentative diagnosis can be made on clinical history of recently applied pharmaceutical drugs, but definitive diagnosis requires PCR or DNA testing. This test is most commonly used for Ivermectin sensitivity but many other drugs are included.
Use of these drugs in ivermectin sensitive patients does not inevitably result in neurological symptoms and veterinarians are recommended to reduce the dosage by 25% in MDR1 carriers and by 30 - 50% in MDR1 affected dogs.
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