MDR1
Go to Washington State University Link for more information.
DESCRIPTION
Some dog breeds are more sensitive to certain drugs compared to other
breeds. For example, Australian Shepherds, Collies, Longhaired Whippets and
other breeds are more sensitive to antiparasitic and anticancer drugs. The
problem is due to a mutation in the multidrug resistance gene (MDR1). The
product of MDR1 gene, P-glycoprotein, is an important component of the
blood-brain barrier that is responsible for pumping many drugs out of the brain.
Dogs with mutant MDR1 gene cannot remove some drugs out of the brain as
normal dogs would, which may result in abnormal neurological signs. The
result may be an illness requiring an extended hospital stay or even death of
the dog.
In addition to its expression in the blood-brain barrier, P-glycoprotein
expression occurs also in the intestinal tract, liver, and kidney. In these
organs, the absence of P-glycoprotein will alter the pharmacokinetic properties
of drugs identified as P-glycoprotein substrates, resulting in enhance oral
bioavailability and/or reducing drug elimination through the liver, kidney, and
gut. In consequence, plasma concentrations will increase and adverse drug
reactivity may occur.
Drugs that have been documented, or are strongly suspected to cause
problems in dogs with MDR1 mutation:
- Acepromazine (tranquilizer):
- Butorphanol (pain control);
- Cyclosporin (immunosuppression drug);
- Digoxin (heart drug);
- Doxorubicin (anticancer drug);
- Ivermectin (antiparasitic drug);
- Loperamide (Imodium®, antidiarrheal drug);
- Moxidectin;
- Vinblastine (anticancer drug);
- Vincristine (anticancer drug).
Biochemical studies have shown that mutant MDR1 gene has the potential to
act on over 50 different drugs. The following drugs may potentially cause
problems when given to dogs that have the mutation:
- Domperidone;
- Etoposide;
- Mitoxantrone;
- Morphine;
- Ondansetron;
- Paclitaxel;
- Quinidine;
- Rifampicin.
INHERITANCE
Multidrug sensitivity in dogs shows an autosomal recessive mode of
inheritance.
DNA TEST
Dogs affected with multidrug sensitivity typically display neurological
symptoms after drug admission such as hypersalivation, ataxia, blindness,
tremor, depression, coma, respiratory compromose, and death. Carriers of the
mutant gene may display mild neurological manifestations. Recently, a
DNA-based test for the detection of the gene responsible for multidrug
sensitivity became available. Since this test directly targets the mutant gene,
it is 100% accurate and provides breeders with definitive information on the
genetic status of their animals. Instead of avoiding drugs as ivermectin in
known susceptible breeds, veterinarians can now determine if a dog is normal,
in which case the drug can be administered, or dog is affected, in which case
an alternative treatment can be given. Breeders can use this information to
detect carriers and eliminate this disease from their breeding lines.
BREEDS:
Australian Shepherd
Collie (rough)
Collie (smooth)
English Shepherd
Longhaired Whippet
McNab
Old English Sheepdog
Shetland Sheepdog
Silken Windhound
Note: As more dogs are tested, more breeds will probably be added to the list
of affected breeds.
TEST RESULTS:
Result Interpretation
Normal/Normal These dogs do not carry the mutation, and will not pass on the
mutation to their offspring. These dogs would not be experiencing unexpected
adverse reaction to normal doses of drugs.
Normal/Mutant These dogs carry both mutant and normal genes, and may pass
on the mutant gene to their offspring. These dogs may experience some
toxicity after normal doses of drugs.
Mutant/Mutant These dogs carry two mutations, and will not pass on the
normal gene to their offspring. These dogs would be expected to experience
toxicity after normal doses of drugs.
Go to Washington State University Link for more information.
DESCRIPTION
Some dog breeds are more sensitive to certain drugs compared to other
breeds. For example, Australian Shepherds, Collies, Longhaired Whippets and
other breeds are more sensitive to antiparasitic and anticancer drugs. The
problem is due to a mutation in the multidrug resistance gene (MDR1). The
product of MDR1 gene, P-glycoprotein, is an important component of the
blood-brain barrier that is responsible for pumping many drugs out of the brain.
Dogs with mutant MDR1 gene cannot remove some drugs out of the brain as
normal dogs would, which may result in abnormal neurological signs. The
result may be an illness requiring an extended hospital stay or even death of
the dog.
In addition to its expression in the blood-brain barrier, P-glycoprotein
expression occurs also in the intestinal tract, liver, and kidney. In these
organs, the absence of P-glycoprotein will alter the pharmacokinetic properties
of drugs identified as P-glycoprotein substrates, resulting in enhance oral
bioavailability and/or reducing drug elimination through the liver, kidney, and
gut. In consequence, plasma concentrations will increase and adverse drug
reactivity may occur.
Drugs that have been documented, or are strongly suspected to cause
problems in dogs with MDR1 mutation:
- Acepromazine (tranquilizer):
- Butorphanol (pain control);
- Cyclosporin (immunosuppression drug);
- Digoxin (heart drug);
- Doxorubicin (anticancer drug);
- Ivermectin (antiparasitic drug);
- Loperamide (Imodium®, antidiarrheal drug);
- Moxidectin;
- Vinblastine (anticancer drug);
- Vincristine (anticancer drug).
Biochemical studies have shown that mutant MDR1 gene has the potential to
act on over 50 different drugs. The following drugs may potentially cause
problems when given to dogs that have the mutation:
- Domperidone;
- Etoposide;
- Mitoxantrone;
- Morphine;
- Ondansetron;
- Paclitaxel;
- Quinidine;
- Rifampicin.
INHERITANCE
Multidrug sensitivity in dogs shows an autosomal recessive mode of
inheritance.
DNA TEST
Dogs affected with multidrug sensitivity typically display neurological
symptoms after drug admission such as hypersalivation, ataxia, blindness,
tremor, depression, coma, respiratory compromose, and death. Carriers of the
mutant gene may display mild neurological manifestations. Recently, a
DNA-based test for the detection of the gene responsible for multidrug
sensitivity became available. Since this test directly targets the mutant gene,
it is 100% accurate and provides breeders with definitive information on the
genetic status of their animals. Instead of avoiding drugs as ivermectin in
known susceptible breeds, veterinarians can now determine if a dog is normal,
in which case the drug can be administered, or dog is affected, in which case
an alternative treatment can be given. Breeders can use this information to
detect carriers and eliminate this disease from their breeding lines.
BREEDS:
Australian Shepherd
Collie (rough)
Collie (smooth)
English Shepherd
Longhaired Whippet
McNab
Old English Sheepdog
Shetland Sheepdog
Silken Windhound
Note: As more dogs are tested, more breeds will probably be added to the list
of affected breeds.
TEST RESULTS:
Result Interpretation
Normal/Normal These dogs do not carry the mutation, and will not pass on the
mutation to their offspring. These dogs would not be experiencing unexpected
adverse reaction to normal doses of drugs.
Normal/Mutant These dogs carry both mutant and normal genes, and may pass
on the mutant gene to their offspring. These dogs may experience some
toxicity after normal doses of drugs.
Mutant/Mutant These dogs carry two mutations, and will not pass on the
normal gene to their offspring. These dogs would be expected to experience
toxicity after normal doses of drugs.
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