DERM NEWS Spring, 2007 by lindash


DERM NEWS Spring, 2007

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									                                                                                                                         Spring, 2007

                                                               DERM NEWS
                                                                            What’s News at Dermcare...
                                   Adverse Drug reactions:
                                     More common than you think?
                                                         Consider the following scenario: An older dog that
   Dermcare-Vet Pty Ltd                                  looks suspiciously like a whippet, only shaggier, has had
      22 Aranda Street
                                                         atopy for years. It has now developed Cushing’s disease
    Springwood QLD 4127
    Phone: 07 3387 9700                                  with generalised Demodex. Horrors, it also has secondary
     Fax: 07 3208 3965                                   Malassezia dermatitis and is extremely pruritic. What is                                   the potential for causing an adverse drug reaction in
                                                         this dog?
     VETERINARIANS                 Drug reactions can and frequently do result in                  Individual Susceptibility to
    Sharyn Mason BSc BVSc          serious harm or death in both human and animal                     Multi-drug Sensitivity
          0408 710 741             patients. Reported figures vary widely but it is
                                   estimated that up to 7% of all human hospital      So why are some breeds and indeed individuals                                                         more susceptible to adverse drug reactions than
                                   admissions each year are attributable to adverse
    Lisa Mason BVSc (Hons)         drug interactions. (1) Whilst largely unknown, the others? The answer lies in the recent discovery
          0408 878 106             incidence of adverse drug reactions in pets is     of a deletion that can occur in the multi-drug       probably lower due in part to fewer drugs          resistance gene (MDR1). The sequence of DNA
                                   prescribed per animal patient vs. human patients.  that is missing encodes the production of P-
 TECHNICAL SALES MANAGER           However, a more likely scenario is that they are   glycoprotein, an efflux transporter that plays a
                                   not being recognised, perhaps erroneously          key role in drug elimination. P-glycoprotein
                                   attributed to disease progression or the onset of  pumps ivermectin and other drugs out of the
          0438 274 548             another disease process. (2)                       brain. Its absence leads to an altered blood brain                                                      barrier function allowing significantly elevated
                                   Recognised or not, they do occur and veterinary plasma levels of these medications, increasing
     TERRITORY SALES               dermatology patients may be particularly at risk the risk of toxicity and abnormal neurological
     REPRESENTATIVES               due to the necessary and frequent use of multiple signs.
       Jayne Gair (QLD/NT)         drugs to achieve the desired therapeutic
           0419 773 376            outcome. Treatment often involves drugs               Approximately 75% of collies in Australia have                                                               the MDR1 gene mutation.(3) Whilst less
                                   that have been implicated in adverse
     Yvette Lim (NSW/ACT)          reactions: namely antibiotic, antifungal,                 common, it can be found in Collie and
            0418 294 961
                                   anti-parasitic and immunosuppressive                       other herding dog crosses. It has also
                                   agents.                                                     been found in many other pure and mixed
      Melissa White (NSW)                                                                       breed dogs, even those that don’t look
          0418 294 395             There are thousands of recognised                            like herding dogs! (4)            A study     drug interactions and probably many                          comprising 4000 pure bred dogs
     Sue Huxley (VIC/TAS)          more that are not. Some may only be                            looking at breed distribution and history
          0429 990 243             reported in human medicine and are                              of the MDR1 mutation           identified
                                   not applicable to veterinary practice.                          several breeds genetically at risk of
      Jessica Cox (VIC/SA)         Conversely, there may be a                                     increased drug sensitivity, amongst
           0416 251 937
                                   significant number of interactions                              them the usual suspects including
                                   that occur only in the species we                               Collies, Australian Shepherds, Old
     Michelle Pardini (WA)         are treating. For this reason, it is
           0427 177 086                                                                            English Sheepdogs and Shetland   unreliable to use the myriad of                                  Sheepdogs. (5)
                                   available on-line drug interaction
        IN THIS ISSUE              checkers that are used by                                        Anecdotal reports in the literature of
   Adverse Drug Reactions &        pharmacists and medical practitioners.             ivermectin sensitivity in sight hounds prompted
     the MDR1 (multi drug                                                             their inclusion in the study. Surprisingly the
       resistance) gene                           Multi-drug Sensitivity              MDR1 mutation was present in 42% of long
      On line plant & grass        We all know to be wary when using ivermectin in haired Whippets (an endearing variation on the
         information at           Collies and related breeds and perhaps avoid norm, not yet recognised as a breed in Australia)
                                   using it at all. But this is only one example of and 18% of Silken Windhounds, the rather
   How we treat demodicosis
                                   breed specific increased susceptibility to serious elaborately named           Borzoi/Whippet cross.
   New Dermcare Sales Team         adverse drug reaction. There are in fact many      Presumably breeders felt that Borpet or Whizi
                                   others…..                                          was never going to catch on!
    Continued from page 1
Although strenuously denied by breeders, the genetics in this pronounced sedation at relatively low dose — could this be
study suggest that it is highly likely that both emerging breeds the connection? It has been suggested that the dose rate of
have crossed paths with a Shetland Sheepdog or two!                ACP be reduced by 25 % in dogs heterozygous for the MDR1
                                                                   deletion and by up to 50% (!) in dogs homozygous for the
The study also concluded that all dogs carrying the MDR1
                                                                   MDR1 deletion.(4) Similar dosage reductions are
mutation are descendents of a single dog from Great Britain
                                                                   recommended when administering butorphanol to affected
before the genetic isolation of breeds by official registry, circa
1873. This is all very interesting but it does have practical
applications for the veterinary industry. It highlights the Research indicates that dogs with the MDR1 deletion are
prevalence of the MDR1 gene mutation in a variety of breeds more likely to have a serious adverse drug reaction including
and their crosses, not just Collies and demonstrates its bone marrow suppression, anorexia, vomiting and diarrhoea
presence in sight hounds that may share unexpected Collie at normal doses of vincristine, vinblastine and doxorubicin. (4,
ancestry. How long before Shoodles (Sheltie x Poodles), 7). Careful monitoring and a reduced dose rate are
Shavaliers (Sheltie x Cavalier) or other Sheltie based recommended for these patients.
designer breeds start popping up in a pet store near you?
                                                                   Drugs that are known to be pumped from the brain by P-
  In summary, the only way to know if an individual dog glycoprotein but considered safe to use in dogs with the
has the mutant MDR1 gene is to have the dog tested. As MDR1 deletion include cyclosporine, digoxin and
   more dogs are tested it is highly probable that more            doxycycline. It is not recommended to empirically change
            breeds will be added to the growing                    dose rates of cyclosporine in these dogs but it is advisable to
               list of known affected breeds.                      undertake therapeutic drug monitoring.(4)
                                                                 It is likely that many drugs routinely used in veterinary
                                       Have you got it?          medicine are substrates of P-glycoprotein and presently,
                                                                 extensive lists are not available.
                                      A blood test is a
                                       more accurate
                                      way to test a dog             Are individual treatment regimes for animals set
                                       for the MDR1-1                             to become a reality?
                                                                    There is clearly an advantage to understanding the MDR1
                                                                    gene status of our veterinary patients. With the
                                                                    availability of a quick, easy and accurate test,
      Detecting Multi-drug Sensitivities in Dogs:
                                                                    veterinarians can screen animals for the MDR1 deletion
             The MDR1-1-delta Gene Test                             prior to administering certain therapeutic drugs and adjust
Researchers at the Washington State University have                 dosing regimes accordingly.
developed a screening test for the presence of the mutant
MDR1 gene. In Australia, Gribbles Molecular Science and             One should exercise extreme caution when administering
Gribbles Veterinary Pathology have an exclusive license from        drugs with a potential to cause neurotoxicity in dogs that
Washington State University to perform the MDR1 DNA test            have the MDR1 mutant-mutant genotype. (7) These dogs
in Australia.                                                       are much more at risk of an adverse drug reaction to
                                                                    many drugs, not just ivermectin.       Dogs that have
This simple test is performed using a buccal swab or EDTA
                                                                    unexpected neurological effects at normal dose rates of
blood sample. The test detects the presence or not of the
                                                                    any drug should have the MDR1-1-delta Gene Test to
gene mutation, providing definitive information on the genetic
                                                                    assess their genetic status.
status of the dog being tested. (6) Dogs homozygous for the
MDR1 gene mutation (abnormal/abnormal) are at risk of
adverse drug reactions at normal dosages. Dogs that are             The availability of the test will not only lead to fewer
heterozygous (abnormal/normal) are considered carriers and          adverse drug reactions but particularly in the case of
may experience adverse reactions at normal drug doses.              ivermectin and demodicosis, allow the treatment of
                                                                    animals based on genotype rather than breed
                  Why test for MDR1-1?                              association.
So how can this information be applied to everyday
veterinary practice? Ivermectin is not the only drug
that is documented to cause problems in dogs with
the MDR1 mutation.        P-glycoprotein has a broad
substrate affinity and can transport a large number                                                                  Can you
of structurally and functionally    unrelated drugs.                                                                  be sure
(7) Acepromazine can cause             profound and                                                                which breed
prolonged      sedation in dogs with the MDR1                                                                       is more at
deletion. Indeed, Rottweilers often show                                                                               risk?
      Continued from page 2

      P-Glycoprotein issues: It doesn’t stop there:
P-glycoprotein deficiencies are not just genetic, they can also                                              Q/ How do
be acquired. Ketoconazole is well recognised as a potent
inhibitor of P-glycoprotein. (8) In fact, ketoconazole will make
                                                                                                             you treat a
any breed of dog have a Collie-like potential for ivermectin                                                 Rhino with
neurotoxicity. Ketoconazole is effectively the medical                                                       dry skin ?
equivalent of an MDR1 deletion, P-glycoprotein
deficiency.      A recent study examining the effects of
ketoconazole on plasma levels of ivermectin found that co-
administered ketoconazole induced higher plasma                                              A/ With
concentrations and longer clearance times of ivermectin. (8) It
has also been demonstrated that the incidence of adverse
effects of     ketoconazole in dogs is higher in dogs on                                   Oatmeal
concurrent      cyclosporine, also a known P-glycoprotein                                 Intensive
inhibitor. (9)                                                                           Conditioner
If we now reconsider the initial scenario with our                                        of course!
whippet cross patient, drugs that could be
considered for the treatment of its various ailments
include: ivermectin (for demodicosis) cyclosporine
                                                                                   The staff at Taronga Zoo
for atopy (Cushingoid, therefore steroids are out)                                      Regularly use
and ketoconazole for Malassezia dermatitis. It is
not hard to see how easily an adverse reaction could
occur if we were not aware of all of the potential                                to help keep the resident
risks of using multiple drug therapies.
                                                                                 Rhinos hides looking great!
The potential for life threatening interactions in
individuals with the MDR1 gene deletion or those                                              The Dermcare Club
taking P-glycoprotein-reversal agents (inhibitors) is                                   Mixed Dozen Bonus is on Again
enormous and something that needs to be carefully                                        1 October, 2007— 28 March, 2008
considered when prescribing drug therapy to our                                     For more information, contact your territory
veterinary patients.                                                            sales representative or visit:
                                                                                         On-line ordering available this year

 1.     Plumb, D. Drug Interactions: The good, the bad and the ugly.
                                                                                                              Information on plants
        21st proceedings of North American Veterinary Dermatology
        Forum. P 83. 2006                                                                                   commonly associated with
 2.     Mealey, K.L. Clinically significant drug interactions. 19th
        Proceedings of AAVD & ACVD annual meeting (North American                                              CANINE ATOPY
        Dermatology Forum) P 45 – 49. 2004
                                                                                                            is available on the Dermcare
 3.     Mealey, K.L. et al. Frequency of the mutant MDR1 allele
        associated with sensitivity in a sample of herding breed dogs                                                  Website
        living in Australia. Vet Parasitol. 131 (3-4): 193-196. 2005
 4.     Multidrug sensitivity. Washington State University, College of
        Veterinary Medicine. Veterinary Clinical Pharmacology Lab.                                         Common name, plant photos and Australian distribution
 5.     Neff, M. W., Robertson, K.R., Wong, A.K. et al. Breed distribution    are listed for a wide variety of trees, weeds and grasses.
        and history of canine mdr1-1 Delta, a pharmocogenetic mutation
        that marks the emergence of breeds from the collie lineage. http://                      See example below: 2004.
 6.                                               Lolium perenne L. Common name: Perennial Ryegrass
 7.     Mealey, K.L. Ivermectin toxicity in herding breeds: molecular
        mechanism and clinical implications. 19th Proceedings of AAVD
        & ACVD annual meeting (North American Dermatology Forum) P
        35 – 39. 2004
 8.     Hugnet, C., Lespine, A., Alvinerie, M. Multiple oral dosing of
        ketoconazole increases dog exposure to ivermectin. J Pharm
        Pharmaceut Sci ( 10 (3): 311-318, 2007.
 9.     Mayer, U.K., Glos, N., Mueller, R.S.           Adverse effects of
        ketoconazole in dogs – a retrospective study. 21st proceedings            This is also a useful tool for owners wanting to
        of North American Veterinary Dermatology Forum. P 143. 2006.                  identify plants in their own backyards
      Continued from page 1

         Demodex: how do we treat it here at
       Animal Allergy & Dermatology Service?
                                                                    Demodicosis with Secondary Pyoderma
There has been much talk about various treatments for                   Pustules, Pimples, Pyoderma
generalized demodicosis. Here at the skin and allergy clinic                Recurrent Hot Spots ?
we still use ivermectin at 350-400mcg/kg once daily orally in
combination with a weekly Pyohex bath and Amitraz rinse.
Antibiotics (primarily cephalexin at 22mg/kg bid) are used         Take care of the skin,
initially, generally for 2-8 weeks depending on the severity
of secondary pyoderma.
                                                                    not just the infection!
We can supply a full vet treatment protocol (including an
ivermectin dose chart) and client information sheet on

                   Other avermectins?

We have seen a number of cases where other avermectins
                                                                                                      Medicated Conditioner
have been used by the referring general practitioner,                                                    Now available
(usually injected weekly) and failed; we have not yet had a                                                In 200 ml
failure when ivermectin has been used as per our protocol
for an adequate length of time (typically 6 months).

                      Amitraz safety?                              In these conditions, the skin is already fragile. Treat it
                                                                   gently with           Medicated Shampoo & Conditioner.
Amitraz is indeed a potent drug and it is recommended that
                                                                               Medicated Shampoo contains an advanced
dogs are not exercised after application of the amitraz for the
                                                                   surfactant base that gently removes scale, crust, sebum and
rest of the day as this can lead to an increased risk of
                                                                   odour associated with bacterial lipases without drying or
toxicity. In the case of very little dogs, it has been suggested
                                                                   stripping the coat of essential lipids.
to apply the amitraz to half of the body one dose and the
other half the following dose. This can help by giving the
                                                                             Medicated Conditioner with leave-in technology
benefits of amitraz with reduced risk of toxicity.
                                                                   reduces the bacterial load on the skin whilst assisting with
                                                                   the retention of skin moisture, improving coat softness,
                 Secondary Pyoderma?                               manageability and shine.
Secondary Pyoderma/Malassezia dermatitis is very common                           New to the Dermcare Team:
in demodicosis and contributes to the degree of associated
pruritus. There is no data to support the concept of
“flushing” mites out of the hair follicle. The pyoderma
associated with demodex should be treated like any other:
gently and with appropriate antimicrobials.

                                                                   Melissa White (above left) has joined Yvette Lim, as Territory
                                                                   Sales      Representative in NSW. Melissa has an Advanced
                                                                   Certificate in Veterinary Nursing and has worked for over 7
                                                                   years in general practice before moving into customer service.
                                                                   Melissa will cover the Northern suburbs of Sydney and Northern
                                                                   NSW, whilst Yvette will continue to call on clinics in South
                                                                   Sydney, Southern NSW and ACT.
                                                                   Jessica Cox (middle) pictured with “Scratchie” is Victoria’s new
                                                                   Territory Sales    Representative.   Jessica has a Diploma in
                                                                   Applied Science (Animal Technology) and has worked at Monash
                                                                   University as an animal research technician.
   Demodicosis (above left), short bodied Demodex
                                                                   Jayne Gair (above right) joins Dermcare as the Territory Sales
   mite (top, right) and demodex associated comedo-
                                                                   Manager for South Brisbane, Gold Coast and Northern New
                    mes. (below, right).                           South Wales. Jayne pictured with daughter Lilly, has 15 years
                                                                   nursing experience including practice management.

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