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Four Way Shoot-Out"Everything you wanted to know about fleas, but were afraid to scratch!"by: John Cargill MA, MBA, MS and Susan Thorpe-Vargas MS, Ph.D. Our choices for flea control agents in the past have been limited to toxic, noxious and other-wise deleterious substances, some of which have been downright dangerous to us, our dogs and to the environment. The standard way of handling fleas has been to go down to the supermarket, garden store, or the veterinarian and buy some form of organophosphate spray for the yard and premises. Organophosphates are commonly used insecticides, many of which are noted for their extremely toxicity to mammals, insects, birds and fish. For quick knockdown on the dog we bought pyrethrin sprays or dips, but none seemed to have a persistent effect. Pyrethrin is a natural insecticide made from several species of the chrysanthemum plant. Some of us will even admit to using organophosphate dips. Sure, the old pyrethrin sprays worked well for a while killing the fleas on the dog, but there always seem to be more where those had come from. While spraying we used to inhale malathion, diazinon and other yard sprays with resultant headaches. We also sprayed yards with heavy doses of insect growth regulators - compounds which interfere with the maturation states through which an insect goes: from egg, larvae and pupa, to adult, disregarding completely the environment and the impact on non-target species that might have been affected at those dosage levels.
Powerful chemicals harm more than fleasSo, what is wrong with using organophosphates and carbamates to control fleas? See Figure 1. What's What in Pesticides for a listing of ingredients and their pesticide categories. Organophosphates and carbamates both have a mechanism of poisoning that works to upset the orderly breakdown of the electro-chemical connection across nerve synapses. That is, they are anti-cholinesterase agents. Acetylcholine bridges the gap between nerve endings allowing electrical current to flow. Cholinesterase breaks down acetylcholine, thus severing the neural connection and preventing continuous stimulation. This basic process is what allows us to think, to move our limbs, and in general, to live. Many of the commonly available organophosphates and carbamates are relatively toxic to dogs and can adversely affect a dog's nervous system even when a lethal concentration has not been achieved.
Organophosphate and carbamate poisoning results in what the authors call the "quivering cockroach syndrome." The poisoned insect (or human or dog) suffers tremors, collapse and even death from over excitation of the nervous system, i.e. they "quiver" on their way to death. Dogs are poisoned every year, especially during the summer months, when owners spray their yards with organophosphates and allow the dogs back on the grass before it has had a chance to dry. As a military weapon, organophosphates have virtually no equal. One drop of VX (US) or of VR-55 (old Soviet Bloc) agent on the skin of an average sized human is enough to kill. Is there any difference between VX or VR-55 and the malathion and diazinon we have been spraying on yards? The answer is: not a whole lot. The mechanism of poisoning is the same; concentration is higher; and the military agents are significantly more effective. For the purposes of this article, let us then conclude that you do not want many of the organophosphate and carbamate pesticides in your immediate environment because of their inherent danger and lack of target species specificity. What are the alternatives? One alternative is to spray the yards and premises with insect growth regulators. Insect growth regulators (IGR's), like Precor®, Ovitrol®, and Siphotrol® have minimal mammalian toxicity (good) but they are relatively non-specific with respect to insects (bad, maybe even very bad). Bugs of all kinds are part of an environmental dynamic equilibrium. Depending upon your purpose in life, there are "good" bugs and "bad" bugs. "Good" bugs such as lacewings, ladybugs, preying mantis and trichogama wasps all prey on "bad" bugs such as aphids, flea larvae and the like. Widespread and heavy use of IGR's can prevent the good, the bad and the ugly bugs from maturing and reproducing. Concerned with the fate of the environment, we strongly recommend you be selective in your use of IGR's and confine their use to limited areas, following label instructions exactly. There is also the question of some IGR products having a carcinogenic effect in mammals.1
New technologies hit their pesty targetOur mission is to convince you, the reader, that in dealing with fleas, unless you are using Bio SpotTM, an over-the-counter flea product, you need to go directly to your veterinarian for one of the new prescription flea control products. This will be a major change in behavior for most dog owners used to picking up a can of flea spray, or an aerosol bomb at the supermarket and getting malathion yard spray at the garden store. Unfortunately, the rules with FDA and EPA and other governmental regulatory bodies in the United States of America are such that it just plain costs too much to get approval to market many products over the counter. Another important point is that because of the client/clinician relationship, your vet is in the right position to assure that proper directions and safeguards are followed. For those not wanting to be tied to their veterinarian's prescription pad for flea control, the only other suitable product available over the counter is Bio SpotTM What follows is our comparison of Frontline® (Rhone Merieux2), Advantage® (Bayer3), Program® (Novartis4) and Bio SpotTM (Farnam Companies5). See Figure 2, Four-Way Shoot-Out! The New Flea Control Chemistries. We will discuss their mechanisms of poisoning or growth regulation, application, costs, safety and effectiveness. See Figure 3. Effects, Duration and Safety. Each product has advantages and disadvantages. As we address the disadvantages, please keep in mind the much greater disadvantages of spraying and dipping with organophosphates, dusting with carbamates, or spraying with insect growth regulators. Some of what we say is technical - but we want you to come away with the concept of the target species specificity of these new products as opposed to the organophosphates and carbamates that kill everything. We intend to make an "air tight case" that all of dogdom should switch to these new technologies in order to better combat the flea and to avoid damaging the environment.
Flea Control PhilosophyGiven that typical flea population demographics are 5% adult, 10% pupae, 35% larvae, 50% eggs, and that eggs and pupae in cocoons are virtually impervious to pesticides, the "choke point" in the flea reproductive cycle that should be attacked is the adult flea. Adult fleas need hosts and blood meals in order to mate. Two options are available: Kill the adults on the host; or disrupt the orderly process of egg-larvae-pupae-adult maturation of the eggs just laid. Going after the 95% of the flea population not on the host can result in the creation of an unhealthy chemically contaminated immediate environment6. We are happy to report the four products reviewed go after adult fleas on hosts, disrupt the egg to adult maturation process, or both.
Long-lasting topical flea adulticidesAdvantageTM --Both AdvantageTM and Frontline® contain neurotoxins that prevent transmission of nerve impulses. Why then do they differ in their toxicity to mammals as opposed to invertebrates? Organophosphate and carbamate insecticides inhibit or prevent the breakdown of the neurotransmitter acetylcholine, thus resulting in hyperstimulation of the nervous system and ending in paralysis and death. AdvantageTM works by preventing acetylcholine from binding to the cell membrane receptor sites of various tissues with a similar hyperstimulation of the excitatory response but has a different mechanism of action. This is far less an insult to mammals than it is to insects. Chemical messengers, such as acetylcholine, can indirectly stimulate or inhibit activity within a tissue type. The particular response depends on the receptor sites of the target tissue and the secondary messenger system invoked by that receptor. There are two types of cholinergic receptors (those that respond to acetylcholine): the nicotinic and muscarinic receptor7,8. Fleas are one of the insect species with a larger percentage of nicotinergic acetylcholine receptors9,10 - it is believed that imidacloprid (the active ingredient in AdvantageTM) preferentially binds to these specific sites. A second hypothesis is that these two receptor sites are more physiologically alike in insects and so their ability to bind imidacloprid to both receptor types are not as specific as in mammals. While there are many structural similarities between the central nervous system (CNS) receptors of some insects and mammals, there are a number of significant pharmacological differences between them. This could account for imidacloprid's low CNS toxicity to fish and mammals (good). Mammals and even some other insect species have a greater proportion of muscarinergic receptors, and thus are less affected than those species with a higher proportion of nicotinergic receptors. This is a major breakthrough in selective specificity to target species. Monthly application is topical between the shoulder blades on small dogs (<55lbs) and between the shoulder blades and forward of the base of the tail in larger dogs. New AdvantageTM 100 packages dosages for large dogs. The cost for a four month supply varies from $30 to $40 for small dogs. AdvantageTM is available only through veterinarians.Frontline® --Frontline® belongs to a rather unique class of insecticides called ion channel blockers. A nerve impulse is no more than an electric current that travels down the length of a nerve cell. Between this cell and other cells is a small space called a nerve synapse that separate the nerve cells. In order for the current to jump this synaptic junction, the electric signals causes the release of neurotransmitters, thus changing the electrical signal into a chemical one. These chemical "messengers" travel across the synapse between nerve cells and bind to their own specific receptors that change the permeability of the cell membrane to various chemical ions. This is how a chemical signal is changed back into an electric signal. Some neurotransmitters, like acetylcholine, "depolarize" (i.e., make more positive) the nerve cell. This causes it to "fire" a nerve impulse. Other inhibitory neurotransmitters, "switch off" nerve conduction by making the cell more negative. This is called hyperpolarization. Gamma aminobutyric acid (GABA) is such an inhibiting neurotransmitter. GABA receptors are part of transmembrane proteins that make little channels in the cell membranes that allow chloride ions to travel into the cell. This mechanism is frequently likened to a "lock and key." When the correct key, i.e., the GABA molecule is inserted into the receptor site, it changes the three dimensional structure or conformation of the protein and opens the door to the chloride ions. There are other receptor sites on this ion channel protein too, and one of these is inside the channel. The active ingredient in Frontline®, fipronil, can bind to this receptor site and even though the GABA key is in the lock, the channel stays closed11,12. In invertebrates, there is a rather good fit between fipronil and the receptor sites so the chloride ions are totally prevented from getting through. Fipronil binds rather poorly to the mammalian receptor sites, and requires considerably higher concentrations to cause an effect on normal hyperpolarization. Thus with fipronil, we have extreme specificity between mammals and invertebrates, making it that much safer for us and for our dogs. The price is competitive with the other products discussed in this article, with the added benefit that Frontline® is also effective against ticks. Safe for puppies as young as eight weeks. Frontline® is available only through your veterinarian.
Systemic IGRProgram® --Program® is more accurately termed an insect development inhibitor (IDI). The active ingredient is lufenuron and its mode of action is to interfere with the synthesis and layering of chitin. Chitin is the major component of the flea's outer body or exoskeleton and is composed of long chain polysaccharides. These sugar moieties are connected in a manner unique to invertebrates, which is one of the reasons that lufenuron is so safe for mammals. In fact, this product is excreted unchanged by both the dog and the flea which leads us to concern for its potential environmental effect. Lufenuron, is potentially highly toxic to aquatic invertebrates, however it is very insoluble in water. Studies have show that it is rapidly broken down by microbial activity under normal aerobic soil conditions and its bioavailability is further reduced in that it binds rapidly to soil particulate matter. Acute toxicity studies using birds and earthworms demonstrated a very low toxicity to these standard reference organisms. When one considers the relatively low residues present in feces, there is little basis for environmental concern. The chief drawback of this product is that the host animal must be bitten by the flea in order for it to be effective. For most normal animals, that is those without flea allergies, this is not a problem; however for those with significant allergies, even one flea bite can result in loss of coat, lesions, etc. Administration is by pill once a month. In terms of the greatest potential safety to children and infants, systemic products, such as Program®, are considered to be among the safest available because there is nothing on the dog to rub off or against which to come in contact13. Especially significant is that puppies as young as 6 weeks may be safely placed on Program®. The cost generally runs between $6 and $7 per month. Program® is available only through veterinary prescription.Bio SpotTM --Bio SpotTM is unique among the new products in that it contains both an adulticide, a long-lasting synthetic pyrethrin (pyrethroid) called permethrin and an IGR, Biolar® (also known as Nylar® and pyriproxyfen). Permethrin is noted for its exceptionally quick and potent "knockdown" properties and for its excellent repellent properties. Permethrin is used throughout the world as a repellent in military clothing, tents, and mosquito nets. The advantage of permethrin is that is has extremely low toxicity to dogs and to humans, yet, as a lipophilic insecticide with a neurotoxic action, it is extremely toxic to insects. Permethrin's mechanism of action is on axons (central conducting core of nerve fiber) through interference with the sodium channel-gating mechanism necessary for the generation and conduction of nerve impulses. Pyrethroids are becoming known as some of the most potent of insecticides and are being recognized as safer alternatives to organophosphates, carbamates and organochlorine insecticides. Their mammal (oral) to insect (topical) toxicity ratio is higher than any other major class of pesticides14:
Given these ratios, it is obvious why pyrethrins/pyrethroids, IGR's and the new chemistries of the products reviewed are heralded as major breakthroughs in safety and environmental friendliness. Furthermore, permethrin is efficiently metabolized by mammalian livers15, and is practically non-toxic to birds16, but is toxic to fish17. Better yet, permethrin binds strongly to soil particles and is nearly insoluble in water, and thus is relatively immobile in a wide range of soil types18. Biolar® (pyriproxyfen) works as a juvenoid growth regulator on embryonic flea eggs and on larvae. Eggs laid by pryriproxyfen-treated fleas within 70 hours after exposure are often devoid of yolk and frequently collapse after being deposited19. Additionally, eggs laid after 70 hours, contained minimal amounts of yolk and no blastoderm (cells formed by cleavage during division of an ovum) was formed, thus effectively halting further maturation. Larval development is similarly arrested. Those fleas not killed outright by the action of the adulticide, will as a result, lay eggs that will fail to develop properly. Application is from a little tube. Small dogs (<33lbs) get one tube dose between the shoulder blades. Big dogs (>33lbs) get one tube between the shoulder blades and one in front of the base of the tail. The large dog packet contains two 30 day treatments for a small dog or one 30 day treatment for a large dog. Manufacturer's Suggested Retail Price is $10.95, and we have seen prices as low as $8.95 through catalog sales. Warning: Bio SpotTM is not suitable for use on cats.
Other related technologiesNematodes (parasitic unsegmented worms of the phylum Nemata characterized by long cylindrical bodies), parasitic wasps, boron and diatomaceous earth (a fine earth composed of the siliceous cell-walls of uni-cellular algae) are additional non-toxic means of ridding the immediate environment of fleas without resorting to noxious substances. Note: the manufacturers of Advantage® and Frontline® claim that their product will rid the immediate environment of the fleas without need of any other products; however, these sorts of claims have been made before by many manufacturers. Time will tell whether these new chemistries are as effective as claimed when put to "field" tests in the dog show and kennel environments. There is no reason to suspect that the claims are less than as stated. Many anecdotal cases have been forwarded to the authors testifying to the efficacy of each one of these products, and we have no reason to disbelieve these dog people whom we have trusted implicitly in the past. Should you have a problem that does not seem to be resolved by Advantage®, Frontline®, Program® or Bio SpotTM we recommend that you use a pyrethrin or permethrin spray for quick knock down, and order a bunch of nematodes and wasps. If that does not do the job, try diatomaceous earth.
ConclusionIf you want to control fleas on your dog and in your environment, the best way to go about it is with one of the four new products reviewed. If you want minimum mammalian toxicity, extreme target species specificity, extreme target species toxicity, ease of use, great tolerance range in the dog, and a way to keep your immediate environment clean, you just cannot do better than Advantage®, Frontline®, Program®, or Bio SpotTM. Each has advantages and disadvantages, but not one has a serious disadvantage. The conclusion we wish to leave you with is this: Get safe. Get on board. Your family and your dogs will appreciate it.
References
Glucosamine is the body's basic starting material for the production
of
the natural shock absorbers and joint lubricants which prevent joint
problems. Glucosamine supplementation "jump starts" the body's
production
of these key elements of the cartilage matrix. As a result, it can
actually help the body to repair damaged or eroded cartilage. Several
studies have shown that glucosamine not only stimulates the production
of
cartilage, but also helps to improve joint function and reduce pain
caused
by osteoarthritis.
Traditional treatments for joint related problems have been
non-steroidal anti-inflammatory drugs (NSAIDS) such as aspirin or
ibuprofen. These agents, however, only treat the symptom (pain),
rather
than the cause of the symptom. As a result these drugs can actually
hasten the deterioration of cartilage by masking the real problem.
Unlike traditional treatments, glucosamine is not a drug. It is a
nutritional supplement that can address the cause of joint pain by
increasing your pet's natural supply of joint compounds. After
years of study and repeated use, glucosamine has no known side
effects.
GlucoTabs(R) provide glucosamine in a scored tablet, formulated with
a
palatable liver base that appeals to dogs and cats alike.
Supplementing
is now as easy as giving your pet a treat. Unlike some competing
products
that must be hidden in, or sprinkled over, your pet's food,
GlucoTabs(R)
leave no question about complete dosing. Most pets love the taste.
GlucoTabs(R) are also very competitively priced. While many
glucosamine
products are known for their upper-end pricing, GlucoTabs(R) average
only
30 to 60 cents per day, depending on the size of your pet.
Additionally,
GlucoTabs do not require a veterinarian's prescription.
Each GlucoTabs(R) tablet contains 500 mg of Glucosamine hydrochloride
in
combination with specifically selected flavor-enhancing ingredients.
Administration typically occurs in two stages: an initial dosing
period
which lasts four weeks, followed by an ongoing maintenance dosage.
If you would like to try GlucoTabs(R) or learn more about
glucosamine supplementation, visit PetPartners web site at
http://www.petpartners.com or call them toll free at
1-888-430-1101. The
PetPartners Web site also provides a detailed chart that will assist
in
determining the correct dosage for your pet.
Editor's Note: Please consult your veterinarian before
administering any OTC vitamins, supplements or medications to your pet. Your
veterinarian will help inform you of proper dosage and let you know if the
product(s) are compatible with your pet's health care
regimen.
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