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DERM NEWS Spring, 2007
DERM NEWS Spring, 2007
Spring, 2007 DERM NEWS What’s News at Dermcare... Adverse Drug reactions: CONTACT US AT 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 www.dermcare.com.au the potential for causing an adverse drug reaction in TECHNICAL SERVICES 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 email@example.com 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 firstname.lastname@example.org 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 KAREN CUNNINGTON BSc BVSc (Hons) 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 email@example.com 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 firstname.lastname@example.org 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 email@example.com 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 firstname.lastname@example.org 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 email@example.com 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 firstname.lastname@example.org 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 email@example.com 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 www.dermcare.com.au 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 dogs. 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? deletion 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: www.dermcare.com.au On-line ordering available this year References: 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 www.dermcare.com.au Veterinary Medicine. Veterinary Clinical Pharmacology Lab. www.vetmed.wsu.edu/depts-VCPL 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: repositories.cdlib.org/postrpints/234. 2004. 6. www.gribblesvets.com.au 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 (www.cspsCanada.org) 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? Treating: 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 request. 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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