A NEWSLETTER OF PRACTICAL MEDICINE FOR VETERINARY PROFESSIONALS                                                           ...
A NEWSLETTER OF PRACTICAL MEDICINE FOR VETERINARY PROFESSIONALS             (S) - methoprene and other IGRs inhibit flea  ...
2 to 10 mg/kg inhibited subsequent             be metabolized to simple acetates that                                     ...
TABLE 1: Insect Growth Regulators (IGRs) and Insect Development Inhibitors (IDIs) Effective Against Fleas on    Companion ...
(text continued from page 3)                                                                The American Kennel Club Welco...
Albert Ahn, DVM, is Vice President of Corporate Communications                   and Veterinary Operations at The Hartz Mo...
Humanitarian Named“Veterinarian of the Year”by Hartz                                                                      ...
Hartz Companion Animal - (S)-Methoprene: Chemical Properties and Applications for Effective Flea Control
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Hartz Companion Animal - (S)-Methoprene: Chemical Properties and Applications for Effective Flea Control

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Successful control of both pet and
environmental flea infestations continues
to challenge the most conscientious of
veterinarians and pet owners. Not only
are newer flea-control agents more
effective and much safer than traditional
agents, they are often available in
convenient formulations. Although
effective products are the basis of
successful flea programs, other factors,
such as pet–owner compliance, climate,
rates of environmental contamination and
flea challenge, pet-owner perceptions of
the severity of the flea problem, and
perhaps resistance, can affect our ability
to eliminate fleas from pets and their
environments successfully.
The developmental cycle

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Hartz Companion Animal - (S)-Methoprene: Chemical Properties and Applications for Effective Flea Control

  1. 1. A NEWSLETTER OF PRACTICAL MEDICINE FOR VETERINARY PROFESSIONALS MARCH 2005 VOLUME 3, NUMBER 1 (S)-Methoprene: Chemical Properties and Applications for Effective Flea Control Byron L. Blagburn Distinguished University Professor Department of Pathobiology College of Veterinary Medicine Auburn University Successful control of both pet and (Figures 1 and 2). Eggs are laid on pets are given flea-control agents before aenvironmental flea infestations continues the host but quickly drop into the large flea population can develop and thento challenge the most conscientious of environment. Larvae hatch from eggs continually throughout the potential fleaveterinarians and pet owners. Not only within a few days and develop through season is most likely to succeed. Insectare newer flea-control agents more three larval stages. The third larval growth regulators (IGRs) are particularlyeffective and much safer than traditional stage spins a silk-like cocoon and effective for this type of preventionagents, they are often available in develops to a fully formed adult within. strategy.convenient formulations. Although Adult fleas emerge from cocoons wheneffective products are the basis of stimulated by host and environmental IN THIS ISSUE:successful flea programs, other factors, factors. The entire developmental cycle (S)-Methoprene: Chemicalsuch as pet–owner compliance, climate, can proceed in as little as 2 weeks in Properties and Applicationsrates of environmental contamination and warm, humid climates, whereas longer for Effective Flea Control........... 1flea challenge, pet-owner perceptions of developmental cycles are seen in cooler,the severity of the flea problem, and drier climates. The American Kennel Club Welcomes the Glen ofperhaps resistance, can affect our ability It is important to remember thatto eliminate fleas from pets and their approximately 95% of the total flea Imaal Terrier .............................. 5environments successfully. population (eggs, larvae, and pupae) resides Ask the Vet ................................ 7 The developmental cycle of fleas in the pet’s environment (Figure 2E). This Humanitarian Named(including Ctenocephalides felis, the can lead to continued pet infestations for “Veterinarian of the Year”common flea of cats and dogs) several weeks after starting treatment. For by Hartz..................................... 8comprises several distinct stages this reason, a prevention strategy in which
  2. 2. A NEWSLETTER OF PRACTICAL MEDICINE FOR VETERINARY PROFESSIONALS (S) - methoprene and other IGRs inhibit flea MARCH 2005 VOLUME 3, NUMBER 1 embryonic development, egg hatch, and/or larval molt Consulting Editors Albert Ahn, DVM Vice President of Corporate Adult flea Communications and Veterinary Egg Larva Pupa Adult flea Operations (first (second The Hartz Mountain Corporation generation) generation) Bruce Truman Divisional Vice President Figure 1— The flea life cycle. Animal Health and Nutrition The Hartz Mountain Corporation (S)-methoprene and other IGRs are flea to continue its development. being used with increasing frequency (S)-methoprene and other IGRs mimic for flea control. Because of their safety JH. Because of the similarity of JH HARTZ® COMPANION ANIMALSM in both humans and animals and their and (S)-methoprene (Figure 4), the is produced for The Hartz Mountain selectivity for insects, they are often (S)-methoprene molecule can Corporation by Veterinary Learning Systems, 780 Township Line Rd., termed biorational insecticides. IGRs successfully bind to the JH receptor in Yardley, PA 19067. target developmental mechanisms the developing flea. This falsely signals present in the eggs and larvae of insects the flea to remain in its present stage. Copyright © 2005 The Hartz Mountain such as fleas but not in pets and people. Since (S)-methoprene differs slightly in Corporation. All rights reserved. This unique feature can be exploited for structure from JH, it is resistant to effective flea control because the degradation by endogenous enzymes. Hartz® and other marks are owned by immature stages are not problematic for The inability of the flea to develop to The Hartz Mountain Corporation. pets. Continued use of IGRs on subsequent stages results in its death. animals or in the environment will Research has shown that Printed in U.S.A. No part of this effectively eliminate environmental (S)-methoprene and other IGRs also publication may be reproduced in any eggs and larvae. This interrupts the affect the development of embryos in form without the express written flea life cycle and results in dramatic flea eggs (embryogenesis) and the permission of the publisher. reductions in problematic adult flea larva’s ability to escape from the egg populations. (S)-methoprene and other (eclosion or hatching) and may disrupt For more information on The Hartz IGRs are often combined with function in a portion of the flea’s Mountain Corporation, visit adulticides to achieve more rapid and digestive system. Other IGRs used to www.hartz.com. effective flea control. control flea infestation include (S)-methoprene and other IGRs pyriproxyfen (Table 1) and fenoxycarb, function by mimicking the effects of which is not currently marketed in the endogenous insect developmental United States. gain regulatory approval in the United hormones (Figure 3). One of these Another class of flea-control agents States and to be widely used. Efficacies hormones, known as juvenile hormone called insect development inhibitors of (S)-methoprene against immature ( JH), is important in the regulation of (IDIs) is also used to control egg and stages of C. felis are well documented. flea development. JH functions to larval flea stages. IDIs function by Studies include those targeting flea eggs maintain the embryonic or larval stage of interfering with the assembly of the and larvae in the laboratory and flea the flea and thus prevents its maturation flea’s chitinous external skeleton. infestations on animals and in the to pupa and adulthood. Development Lufenuron is the only IDI currently environment. Studies also include the proceeds only after JH is enzymatically marketed for flea control in the United use of (S)-methoprene alone and in destroyed by esterases in the flea’s States (Table 1). combination with adulticidal flea circulatory system. Decreased (S)-methoprene, a terpenoid compounds. Applying (S)-methoprene concentration of JH is the signal for the compound, was the first of the IGRs to to the hair of dogs and cats at rates of2 HARTZ COMPANION ANIMAL ® SM • MARCH 2005 • VOL. 3, NO. 1
  3. 3. 2 to 10 mg/kg inhibited subsequent be metabolized to simple acetates that Adevelopment of C. felis eggs to adult fleas. were subsequently incorporated intoIn vitro studies of (S)-methoprene fatty acids, lactose, and cholesterol.incorporated into flea-rearing media at (S)-methoprene metabolites did notconcentrations of 0.01 to 0.03 ppm accumulate in tissue. Unmetabolized(0.001–0.003 mg/g of media) prohibited (S)-methoprene was excreted in feces99% of 3.5-day-old flea larvae from (80%) and urine (20%).developing to adult fleas. These same Another indication of the safety ofstudies also demonstrated that (S)-methoprene is its approval by the(S)-methoprene interfered with flea World Health Organization (WHO) for Blarvae’s ability to successfully spin a incorporation into drinking water forcocoon. (S)-methoprene is marketed in mosquito control. WHO contends thatnumerous formulations designed for (S)-methoprene poses no risk to humans,application on dogs and cats (Table 2). animals, or the environment. Since Because of their unique mechanism (S)-methoprene is metabolized orof action, (S)-methoprene and other degraded to simple products in theIGRs are among the safest insecticides animal’s body and the environment, it isknown. An oral dose of up to 34,600 unlikely to accumulate in plant andmg/kg in rats did not result in adverse animal food products.reactions. In dogs, the amount necessary (S)-methoprene provides severalto cause serious toxicity and death is distinct advantages when combined withbetween 5,000 and 10,000 mg/kg, a flea adulticides:dose that would be impossible to Cachieve using currently available • (S)-methoprene kills eggs produced byproducts. Similar safety profiles for adult fleas that survive between(S)-methoprene were reported in swine, applications of adulticidal agents.sheep, cattle, rabbits, hamsters, and • (S)-methoprene exerts its effects inguinea pigs. Safety studies also indicated such small concentrations, its residualthat pure (S)-methoprene was not activity exceeds that of topicalirritating when applied to the skin or adulticides. When pet owners stopeyes. However, it is important to using flea products because they noremember that topical formulations of(S)-methoprene and other flea-control longer see any fleas, (S)-methoprene in D combination products provides someagents may contain other componentscapable of causing dermal irritation or residual protection against eggs.sensitivity. • (S)-methoprene’s mechanism of action Because topically applied differs from that of adulticides, so it is(S)-methoprene may be ingested through unlikely that fleas could becomegrooming by dogs and cats, it is resistant to the effects of both agentsnecessary to explain the fate of orally in combination products.ingested (S)-methoprene in animals.Radiolabeled (S)-methoprene In summary, because of their potent Eadministered orally to cows appeared to activity, unique mode of action, and (text continues on page 5)Figure 2— (A) Flea eggs (Ctenocephalides felis). (B) Flea larva (C. felis). Thelife cycle of fleas includes three larval stages. (C) Flea pupae (C. felis). This stage,also known as a cocoon, contains preemerged adult fleas. (D) Adult female flea(C. felis). Note the comb-like structures below the eyes and behind the head.(E) Eggs, larvae, and pupae of C. felis at the base of an indoor carpet. Ninety-five percent of the flea life stages live off the host. HARTZ® COMPANION ANIMALSM • MARCH 2005 • VOL. 3, NO. 1 3
  4. 4. TABLE 1: Insect Growth Regulators (IGRs) and Insect Development Inhibitors (IDIs) Effective Against Fleas on Companion Animals IGR or IDI Product Names Formulation(s) Target Stage Lufenuron (IDI) Program, Sentinel (Novartis Flavored tablet, oral suspension, Eggs Animal Health) injectable suspension Pyriproxyfen (IGR) Many, including Bio Spot and Spot-on, spray, shampoo, collar Adultsa, eggs, larvae Scratchex (Farnam Companies), KnockOUT (Virbac), EctoKyl (DVM Pharmaceuticals), and PreTect (Sergeant’s Pet Care Products) (S)-Methoprene (IGR) Many (see Table 2) Spot-on, spray, shampoo, collar Adultsa, eggs, larvae aProducts effective against adult fleas also contain adulticides. TABLE 2: Examples of Flea Control Products that Contain (S)-Methoprene Product Name (Manufacturer) Host Species Formulation Ingredients Target Parasites Frontline Plus (Merial) Dogs, cats Topical spot Fipronil, (S)-methoprene Fleas (adults, eggs, treatment larvae) Ticks (all stages) Hartz® ADVANCED CARE® Dogs, cats Topical spot Phenothrin, (S)-methoprene Fleas (adults, eggs, 4 in 1 Plus+ (The Hartz treatment larvae) Mountain Corporation Ticks (adults) Mosquitoes (adults) Sergeant’s Double Duty Flea Dogs, cats Collar Propoxur, (S)-methoprene Fleas (adults, eggs, & Tick Collar (Sergeant’s Pet larvae) Care Products) Ticks (all stages) Vet-Kem Ovitrol Plus Flea & Dogs, cats Shampoo Pyrethrin, piperonyl butoxide, Fleas (adults, eggs, Tick Shampoo (Wellmark (S)-methoprene larvae) International) Ticks (all stages) Mechanism of action of (S)-methoprene and other IGRs Juvenile Hormone (JH) Enzymes Juvenile Hormone (JH) ( S)-methoprene cannot remove Enzymes (S )-methoprene remove JH JH JH receptor receptor Egg/larval Inhibition of Egg or larva Egg or larva development development Fleas not exposed to ( S)- methoprene Fleas exposed to (S) -methoprene Figure 3— Mechanism of action of (S)-methoprene and other IGRs.4 HARTZ COMPANION ANIMAL ® SM • MARCH 2005 • VOL. 3, NO. 1
  5. 5. (text continued from page 3) The American Kennel Club Welcomes A the Glen of Imaal Terrier O O H OC H 3 The Go-To Glen B T he American Kennel Club welcomes the O O multifunctional, even-tempered, and powerfully built O Glen of Imaal Terrier, who joins his cousins, the Kerry Blue, Soft Coated Wheaten, and Irish terriers, in the registry.Figure 4— Note the similar A TOUGH TERRAIN, AN EVEN TOUGHER TERRIERchemical structures of juvenile hor- The Glen of Imaal Terrier is indigenous to the wild and barren place from whichmone III (A) and (S)-methoprene (B). he takes his name. The region’s farmers, descendents of Flemish and Hessian soldiers, developed the breed in the 17th and 18th centuries in this area located on Ireland’senhanced activity against flea eastern seaboard. Surviving in this bitter locale required every resource available to thedevelopmental stages when combined farmer, and a dog who could not make himself useful would not last long.with adulticidal agents, (S)-methoprene Though the smallest of the four Irish terrier breeds, the Glen is exceptionally heavy-boned and sturdy. Long and low to the ground, with powerful head and legsand other IGRs or IDIs can contribute bowed, the breed guarded stock, hunted badger, fox, and otter, and dispatched verminsignificantly to the successful control of of all sorts around the farmstead. The Glen was purposely developed closer to thefleas and flea-induced diseases. A flea- ground and stockier than other terriers. This made them optimal badger dogs—theircontrol strategy that combines adulticides punishing jaws and short-legged bodies enabled them to spar with their stronger,with IGRs and/or IDIs will likely achieve fiercer quarries. When digging, the bowed front legs and turned-out feet were ideal forboth faster and longer-lasting flea throwing dirt to the sides rather than back in the hole.control. HAIRY AND HEALTHYSUGGESTED READING The Glen is meant to be shown with a natural coat. This double-coated breed withBlagburn BL, Clekis T, Dryden MW, et al: Integrated a silky undercoat mixed with a wiry outercoat does not require the scissoring skill flea control: Effective strategies to minimize needed for Kerries and Soft Coated Wheatens, nor is frequent stripping required. This resistance. Lenexa, KS, Veterinary Healthcare does not mean that the Glen—a harsh-coated breed—has no grooming needs. Communications, 2002. Brushing regularly and stripping once or twice annually will prevent almost allBlagburn BL: Advances in ectoparasite control: Insect shedding. Clippers, however, are not an option. growth regulators and insect development inhibitors. Most experts agree that the Glen is blessedly free of hereditary defects, though any Vet Med 91:9–14, 1996. breed can carry recessive genes for a range of universal defects. Rare cases of theEl-Gazzar LM, Koehler PG, Patterson RS, Milo J: common genetic disorder progressive retinal atrophy have been reported. Hip dysplasia Insect growth regulators: Mode of action on the cat flea, Ctenocephalides felis (Siphonaptera: Pulicidae). is found in most breeds, including Glens. Like all terriers, the Glen can be afflicted J Med Entomol 25:651–654, 1986. with skin irritations, usually as a result of flea allergies, although there are fewerGarg RC, Donahue WA: Pharmacologic profile of problems than previously thanks to selective breeding. methoprene, an insect growth regulator, in cattle, dogs, and cats. JAVMA 194:410–412, 1989. A STUDY IN CONTRASTSOlson A: Ovicidal effects of the cat flea, Ctenocephalides One of the charms of this “Irish Gladiator” is that he is a bit of a paradox. Even felis (Bouch), of treating fur of cats and dogs with though the Glen is known for his intensity, he is a placid, agreeable family dog whose methoprene. Int Pest Control 27:10–16, 1985. fans claim is less excitable than some of the other members of his group.Palma KG, Meola SM, Meola RW: Mode of action of While the Glen can be stubborn with game, he takes easily to obedience training; pyriproxyfen and methoprene on eggs of he is gentle with children yet will not shy away from defending himself. He is small in Ctenocephalides felis (Siphonaptera: Pulicidae). J Med Entomol 30:421–426, 1993. stature, but his guttural bark and stocky body give him an appearance of might, making him an excellent little watchdog. He responds well to praise and is sensitive toRust MK, Dryden MD: The biology, ecology, and management of the cat flea. Annu Rev Entomol scolding. Fans of the Glen warn, however, that his complex character means he is not 42:451–473, 1997. the perfect fit for every household.Siddall JB: Insect growth regulators and insect control: Committed fanciers have maintained the Glen’s status as a substantial and diligent A critical appraisal. Environ Health Perspect worker and a pleasing and affectionate companion. Unless, of course, you are a badger. 14:119–126, 1976. HARTZ® COMPANION ANIMALSM • MARCH 2005 • VOL. 3, NO. 1 5
  6. 6. Albert Ahn, DVM, is Vice President of Corporate Communications and Veterinary Operations at The Hartz Mountain Corporation. ASK TH E VETQ Is the ongoing use of the insect growth regulator methoprene sufficient to control fleas in a single-pet home? Q What natural ways can pet owners help control fleas in the environment?A Methoprene is a synthetic insect growth regulator or juvenile hormone mimetic and is further classified as A The nematode Steinernema carpocapse parasitizes fleas and is sometimes used for flea control. The nematodes enter the flea larvae and then excrete a a terpenoid. Juvenile hormones maintain the larval bacterial compound that breaks down the larvae’s stage in the insect or prevent metamorphosis; when internal organs. Unfortunately, the nematodes cannot the level of juvenile hormone drops, pupal and adult establish themselves well in the environment, and developmental stages begin. Methoprene is ovicidal they have to be applied repeatedly (every month) to when female fleas are exposed on the pet and provide effective flea control. larvicidal in the environment. Other ways to help control fleas include: Insect growth regulators are critical components in integrated pest management for total control of fleas. • Frequent vacuuming of the pet’s environment. They do not have a direct kill effect on adult fleas but After vacuuming, the bag should be placed in a will help decrease the flea population by blocking flea plastic bag and placed in an outdoor trash egg production. However, in the case of a current receptacle. This prevents emergence of new fleas flea infestation, it is best to use an insect growth from the immature stages in the vacuum bag. regulator in combination with insecticidal treatments to help kill adult fleas. • Grass should be kept short by mowing frequently. Immature flea stages can be destroyed by direct sunlight; so keeping the lawn short helps decrease the number of emerging fleas.Articles found in the Hartz Companion Animal SM newsletter can be copied and distributed to your colleagues, staff, and clients. Additional newsletters may also be obtained by contacting us at feedback@hartz.com or by phone at 800-275-1414. WE WANT TO HEAR FROM YOU! • Have questions or comments? Call our Consumer Relations Department at 800-275-1414 and ask to speak to a Hartz staff veterinarian or email us at feedback@hartz.com. • To obtain a Hartz Veterinary Catalog of products, please call 800-999-3000 x5118 or email us at feedback@hartz.com. HARTZ® COMPANION ANIMALSM • MARCH 2005 • VOL. 3, NO. 1 7
  7. 7. Humanitarian Named“Veterinarian of the Year”by Hartz Dr. Earl O. Strimple, left, receives the 2005 Veterinarian of the Dr. Earl O. Strimple, a leader in the movement to elevate Year award from Dr. Albert Ahn, Vice President of Corporate the human condition through soothing interactions with Communications and Veterinary Operations at Hartz. animals, has been named Veterinarian of the Year for 2005 by The Hartz Mountain Corporation. He was nominated for the award by Ms. Margery Yeager, Over the past 25 years, Dr. Strimple has spearheaded a whose family pets were treated by Dr. Strimple for over 20 range of programs bringing dogs, cats, rabbits, and other years. She has also been a PAL volunteer. “Through this companion animals into direct contact with hospital patients, program, many lives are touched with the healing presence of nursing home residents, prison populations, disadvantaged animals,” she said. “Dr. Strimple does all of this work with children, hospice patients, and more. The program that he dedication and humility. He deeply deserves to be rewarded for heads in Washington, DC, presently makes regular visits to his excellent practice as a veterinarian and his substantial Walter Reed Army Hospital in Bethesda, MD, where trained contributions to often overlooked populations in the volunteers and their pets spend time with severely wounded community.” soldiers returning from Iraq and Afghanistan. The runners up for 2005 were Dr. Lee Morgan of the “Dr. Strimple’s compassionate volunteers have quietly Georgetown Animal Hospital in Washington, DC, and Dr. enriched the lives of thousands of adults and children,” said Lori Civello of the Glendale Animal Hospital in Glendale Dr. Albert Ahn, Vice President of Corporate Communications Heights, Illinois. Dr. Morgan trains service dogs for the Seeing and Veterinary Operations at Hartz. “We salute Dr. Strimple’s Eye Foundation and The Guide Dogs for the Blind, and his tireless efforts to promote the human–animal bond through hospital provides support for a variety of rescue foundations community outreach, and we are proud to give this award to and animal shelters. Dr. Civello runs an adoption program such an outstanding individual.” through her hospital. She also works with many shelters and Dr. Strimple, who practiced veterinary medicine for over 30 rescue groups to provide discounted care, spays, and neuters to years and founded the not-for-profit organization PAL animals awaiting new homes. Drs. Civello and Morgan each (People Animals Love), will receive the grand prize of $5,000. received a $2,500 award.Veterinary Learning Systems PRESORTED STANDARD780 Township Line Road U.S. POSTAGEYardley, PA 19067 PAID BENSALEM, PA PERMIT #118 401227

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