Arthritis
Allergies
Anxiety
Ear Infections
Flea & Tick
Heart Problems
Heartworm
Hot Spots
Hyperthyroidism
Hypothyroidism
Incontinence
Shedding Control
Skin Irritation
Tear Stains
Urinary Infections
Vomiting/Diarrhea
Weight Management
Worms
See All A-Z
Arthritis
Allergies
Anxiety
Ear Infections
Flea & Tick
Heart Problems
Heartworm
Hot Spots
Hyperthyroidism
Hypothyroidism
Incontinence
Shedding Control
Skin Irritation
Tear Stains
Urinary Infections
Vomiting/Diarrhea
Weight Management
Worms
See All A-Z
Breath Fresheners
Chews & Treats
Rinses & Water Additives
Toothpaste & Toothbrushes
Ear Cleansers
Ear Infection Remedies
Ear Mite Treatments
Antibiotic Anti-Infective
Artificial Tears & Lubricants
Eye Inflammation
Glaucoma
Tear Stain Removers
Flea & Tick Prevention
Heartworm & Flea Control
Home Flea & Tick Treatment
Oral Flea Treatments
Pet Flea & Tick Control
Tick & Flea Collars
Canned Pet Food
Dry Pet Food
Raw Pet Food
Adult Pet Food
Hypoallergenic
Glucose Balance
Digestive Health & Support
Grain Free
Joint Support
Kitten Food
Puppy Food
Senior Pet Food
Skin Support
Small Breed Dog Food
Weight Loss & Management
Treats
Pet Food Storage
Joint Pain
Joint Supplements
Lifting Harness
Orthopedic Beds
Steps & Ramps for Mobility
Allergy Relief
Antibiotics
Antifungal
Anxiety
Asthma
Compound Medications
Cough Relief
Digestive Health & Enzymes
Diuretics
High Blood Pressure
Hormonal Endocrine
Insulin & Glucose Balance
Motion Sickness & Nausea
Pain
Seizure Disorder
Thyroid
Urinary Tract & Kidneys
Wormers
Beds
Bowls & Elevated Feeders
Carriers
Car Seats & Pet Carriers
Cat Litter
Cesar Millan Training Aids
Crates & Kennels
Drinking Fountains
Elizabethan Collars
First Aid
Furniture
Furniture Protectors
Gates
Grooming Tools
Holiday
Leashes & Harnesses
Life Jackets
Outdoor Cat Pens
Pet Food Storage
Shampoos
Stain Removers
Steps & Ramps
Strollers
Toys
Training Aids
Treats
Wireless Dog Fences
Antibacterials
First Aid
Fish Oils & Omega 3
Fly Control
Grooming Tools
Hairball Remedies
Itch Relief
Ringworm Treatments
Shampoos
Shedding Control
Skin Care Supplements
Skin Medications
Antioxidants
Calcium
Dietary
Digestive Enzymes
Fish Oils & Omega 3
Liver Support
Multivitamins
Potassium
Senior Support
Whole Food Supplements
   
 
 
 
Working Dog Breed Info
 

Sign Up for Pet Health Articles & More

Email:

 
 
Share on Facebook Share on Twitter

Pet Medication Sensitivity in Herding Dogs

  
 

Herding Dogs with Resistance and Sensitivity to Pet Medications


In the past 20 years, many herding dogs have experienced side effects and reactions to certain medications due to the Multi Drug Resistant 1 (MDR1) gene, which can cause normal doses of drugs to have toxic effects. In addition, more than 30 potentially toxic drugs have been identified, and a lab test has been developed to identify dogs with the abnormal MDR1 gene.In addition, more than 30 potentially toxic drugs have been identified, and a lab test has been developed to identify dogs with the abnormal MDR1 gene.

We now recognize three different factors that contribute to drug toxicity especially common in herding dogs: a genetic mutation, drugs that inactivate normal cell pumps, and substances that inactivate cell enzymes so they cannot break down drugs.  The following sections explain how these factors cause drug toxicity:

  1. The cell pump (P-glycoprotein) and the MDR1 gene,
  2. The role of cell enzymes (CYP3A),
  3. Which herding-breed dogs have the MDR1 gene,
  4. Which drugs can become toxic if not pumped out by
    P-glycoprotein,
  5. Which drugs inactivate normal P-glycoprotein pumps,
  6. What happens when dogs with the MDR1 gene take drugs they should avoid, and
  7. How to have your dog tested.

  
Herding dogs can be predisposed to have multi Drug Resistant gene MDR1
  
  • Some herding dogs have a gene that causes drug sensitivity.
  • Laboratory tests can determine which dogs have drug sensitivities.
  •   
      

    What is the role of the P-glycoprotein pump and the Multi Drug Resistant 1 (MDR1) gene?



    Cells are like little cities and have methods of removing waste and toxic materials. One removal method is a protein pump that sits on the cell membrane and pumps materials out. This is called P-glycoprotein, which means it contains both sugars (glyco) and proteins. A gene codes for the P-glycoprotein pump, and some dogs inherit a healthy gene; others, a gene that has mutated. The mutated gene, the Multi Drug Resistant 1 (MDR1) gene, codes for a defective P-glycoprotein that cannot pump drugs from the cell. Thus, drugs accumulate and have a toxic effect even when given at normal doses.

    Dogs inherit genes from both their sire and dam so that they can have one defective gene or they can have two defective genes. Dogs with one defective gene (heterozygous for the defect) have less severe symptoms than dogs with two defective genes (homozygous for the defect).

    What Role Do Cell Enzymes (CYP3A) Play?


    In addition to having proteins on the membrane that remove drugs from the cell, most cells have enzymes that break down drugs and inactivate them. Cytochrome P 450 (CYP 450) is a family of enzymes that inactivates about 60% of drugs used in pets. One of the CYP 450 family—CYP3A—can be blocked or inactivated by ketoconazole and by grapefruit juice. With CYP3A inactivated, drugs reach toxic concentrations within cells.

    Dogs can have both the defective MDR1 gene and have inactivated CYP3A enzymes. These dogs are very likely to develop toxicity with certain drugs.

    Which Herding-Breed Dogs Have the MDR1 Gene?


    • Australian Shepherd
    • Australian Shepherd Mini
    • Border Collie
    • Collie
    • English Shepherd
    • German Shepherd
    • McNab
    • Old English Sheepdog
    • Shetland Sheepdog
    • Mix breeds with any of the above

    Two sighthound breeds have the MDR1 gene:

    • Longhaired Whippet
    • Silken Windhound

    Which Drugs Become Toxic If Not Pumped Out by P-glycoproteins?



    Many different drugs are normally pumped from cells by P-glycoproteins: anticancer drugs, antiparasitics, antibiotics, cardiac drugs, immunosuppressants, opioids, steroid hormones, and miscellaneous drugs. The following is an alphabetical list of some of the drugs that can become toxic in dogs with the MDR1 mutation:

    • Abamectin
    • Acepromazine
    • Actinomycin D
    • Aldosterone
    • Amitriptyline
    • Butorphanol
    • Cortisol
    • Cyclosporine
    • Dexamethasone
    • Digoxin
    • Diltiazem
    • Docetaxel
    • Domperidone
    • Ketoconazole
    • Doxorubicin
    • Doxycycline
    • Erythromycin
    • Etoposide
    • Itraconazole
    • Ivermectin
    • Levofloxacin
    • Loperamide
    • Methylprednisolone
    • Milbemycin
    • Morphine
    • Moxidectin
    • Ondansetron
    • Paclitaxel
    • Selamectin
    • Sparfloxacin
    • Tacrolimus
    • Talinolol
    • Terfendadine
    • Tetracycline
    • Vecuronium
    • Verapamil
    • Vinblastine
    • Vincristine

    Which Drugs Inactivate Normal P-glycoprotein Pumps?



    Some dogs have normal P-glycoprotein pumps (they don't have the MDR1 mutation), but their P-glycoprotein pumps are inactivated by certain antidepressants, antibiotics, cardiac drugs, immunosuppressants, opioids, and miscellaneous pharmaceuticals. When the pumps are inactivated, dogs experience toxic overdoses of drugs normally cleared by the pump. The following items inactivate normal P-glycoprotein pumps:

    • Amiodarone
    • Bromocriptine
    • Carvedilol
    • Chlorpromazine
    • Cyclosporine
    • Erythromycin
    • Fluoxetine
    • Grapefruit juice
    • Itraconazole
    • Ketoconazole
    • Methadone
    • Nicardipine
    • Paroxetine
    • Pentazocine
    • Quinidine
    • Saint John's Wort
    • Tacrolimus
    • Tamoxifen
    • Verapamil

    Any dog—whether with normal P-glycoproteins or abnormal P-glycoproteins—is at risk for developing drug toxicity when taking the above items in conjunction with medications normally cleared by P-glycoproteins.

    What Happens When Dogs with the MDR1 Gene Take Drugs They Should Avoid?



    The range of symptoms that dogs exhibit when they have the MDR1 gene mutation depends upon the nature of the drug they take. As examples, here are descriptions of symptoms caused by cancer drugs, ivermectin, digoxin, acepromazine, and opoids.

    Cancer drugs
    When dogs with cancer in organs that express the MDR1 gene (placenta, brain, kidneys, intestines, gallbladder, and testes) are given the anticancer drug doxorubicin, they have two problems. First, the doxorubicin has no effect on the cancer and the tumor is said to be chemotherapy resistant. Second, the dog develops severe diarrhea, bone marrow suppression, and loss of appetite.

    Ivermectin
    Ivermectin is an antiparasitic. It is used at low doses to kill heartworm microfilaria and at higher doses to treat mange. When herding dogs with MDR1 gene mutation are given Ivermectin to treat mange, they experience central nervous system (CNS) effects: cranial nerve abnormalities, coma, hyper salivation, dilated pupils, loss of balance (ataxia), and poor reflexes.

    Digoxin
    Digoxin is given to dogs with weak hearts, such as occurs with congestive heart failure. Herding dogs with MDR1 gene mutation develop anorexia, vomiting, and cardiotoxicity if given normal doses of digoxin.

    Acepromazine
    Acepromazine is given to calm dogs, but it puts dogs with MDR1 gene mutation into a stupor.

    Opoids
    Opoids (loperamide, butorphanol, and morphine) are given to stop diarrhea (loperamide) and to relieve pain (butorphanol and morphine). When these drugs are given to dogs with MDR1 gene mutation, they become stuporous.

    How Can Dogs Get Tested?



    The Veterinary Clinical Pharmacology Lab (VCPL) at the College of Veterinary Medicine at Washington State University developed a test that identifies dogs carrying the MDR1 gene. The lab can determine whether a dog has a single abnormal gene or two abnormal genes. Dogs with two abnormal genes (homozygous for the genetic mutation) experience the most severe problems with toxicity if given drugs listed above. When veterinarians have this information, they can decrease the dose if dogs must have any potentially toxic drugs.

    To order a test, phone 509-335-3745, or visit the Veterinary Clinical Pharmacology Lab's web site www.vetmed.wsu.edu/vcpl and use the contact information. Instructions for collecting the sample from inside your dog's mouth are on the website. The lab charges $60.00 and completes the test within 3-5 days. Discounts are available if five or more dogs are tested.

    Summary



    Tremendous mental and physical demands are placed on herding dogs. We can avoid causing them any unnecessary problems with toxicity if we understand their potential for sensitivity to certain drugs. Sensitivity is caused by inheriting the Multi Drug Resistant 1 (MDR1) gene, by taking drugs that inactivate normal P-glycoproteins, or by taking substances that inactivate the CYP3A enzyme. With knowledge and support, our herding dogs can stay healthy and reach their full potential.

     
     
      

      
     
    Max's Tip: Dogs can be affected by the MDR1 gene whether they are purebred or mixed bred.  
      

     
     
       
    Help / Customer Service
    My Account
    PetMeds® Sites
    PetMeds® Programs
    Our 100% Guarantee
    About Us
    Contact Us
    FAQs
    PetMeds® Help
    Privacy Policy
    Printable Order Form
    Site Map
    Testimonials
    Vet Directory
    Request a Catalog

    Home
    Login
    Email Preferences
    Reorder
    Easy refill
    Track my order
    My Account Page
    My pet has passed away
    PetMeds® Blog
    PetHealth 101®
    PetMeds® Charitable Causes
    1-800-PetMeds® Careers
    PetMeds® Investor Relations
    pet meds
    Pet Meds Photos
    Pet Meds News
    Pet Health Articles
    Affiliate Program
    Corporate Program
    Shelter & Rescue Program
     
    Join our Social Network
     
        PetMeds® on Facebook
        PetMeds® on Twitter
        PetMeds® on YouTube
        PetMeds® Google+
        PetMeds® LinkedIn
    Copyright © 2014 PetMed Express, Inc. All Rights Reserved.
       
     
    Vet-VIPPSVETERINARY-VERIFIED INTERNET PHARMACY PRACTICE SITES(CM) Online Veterinary Pharmacy Services
     
    1800PetMeds.com has earned Veterinary-Verified Internet Pharmacy Practice Sites(CM) (Vet-VIPPS(CM)) accreditation through the National Association of Boards of Pharmacy® (NABP®).
    Verisign Secured Click for the BBB Business Review of this Pharmacies in Pompano Beach FL 1800PetMeds.com is rated ELITE by STELLAService.