Ectoparasiticidals for Animal Use

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ECTOPARASITICIDALS FOR ANIMAL USE ____________________________________________________________ ____________ Arthropod parasites (ectoparasites) are a major cause of production losses in livestock throughout the world. In addition, many arthropod species act as vectors of disease for both animals and humans. Treatment with various drugs to reduce or eliminate ectoparasites is therefore often required to maintain health and to prevent economic loss in food animals. The choice and use of ectoparasiticides depends to a large extent on husbandry and management practices, as well as on the type of ectoparasite causing the infestation. Accurate identification of the parasite or correct diagnosis based on clinical signs is necessary for selection of the appropriate drug. The selected agent can be administered or applied directly to the animal, or introduced into the environment to reduce the arthropod population to a level that is no longer of economic or health consequence. Parasites that live permanently on the skin, such as lice, keds, and mites, are controlled by directly treating the host. Some mange mites burrow into the skin and are therefore more difficult to control with sprays or dips than are lice and keds, which are found on the surface of the skin. However, once these obligate parasites are eradicated, reinfection occurs only from contact with other infected animals Nonpermanent parasites (ticks, flies, etc) are less easily controlled because only a small proportion of the population can be treated at any one time, and other hosts may maintain them. 1

description

a brief overview of the ectoparasiticidal agents available for animal use

Transcript of Ectoparasiticidals for Animal Use

Page 1: Ectoparasiticidals for Animal Use

ECTOPARASITICIDALS FOR ANIMAL USE

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Arthropod parasites (ectoparasites) are a major cause of production losses in livestock throughout the world. In addition, many arthropod species act as vectors of disease for both animals and humans. Treatment with various drugs to reduce or eliminate ectoparasites is therefore often required to maintain health and to prevent economic loss in food animals.

The choice and use of ectoparasiticides depends to a large extent on husbandry and management practices, as well as on the type of ectoparasite causing the infestation.

Accurate identification of the parasite or correct diagnosis based on clinical signs is necessary for selection of the appropriate drug.

The selected agent can be administered or applied directly to the animal, or introduced into the environment to reduce the arthropod population to a level that is no longer of economic or health consequence.

Parasites that live permanently on the skin, such as lice, keds, and mites, are controlled by directly treating the host.

Some mange mites burrow into the skin and are therefore more difficult to control with sprays or dips than are lice and keds, which are found on the surface of the skin. However, once these obligate parasites are eradicated, reinfection occurs only from contact with other infected animals

Nonpermanent parasites (ticks, flies, etc) are less easily controlled because only a small proportion of the population can be treated at any one time, and other hosts may maintain them.

Some tick and mite species stay on the host only long enough to feed, which may be as short as 30 min, or as long as 21 days. Biting flies, such as the horn fly, can be found continuously on the backs and undersides of cattle, where they suck blood up to 20 times a day; other biting flies (such as stable flies and horse flies) and mosquitoes feed to repletion, then leave the animal to lay eggs.

Nonbiting flies, such as the face fly or the house fly, may visit infrequently but can be very annoying and may transmit disease agents. Larvae of certain blowflies live on the skin or in tissues of sheep and other animals and cause cutaneous myiasis.

Larvae of other flies spend several months inside animals, eg, nasal bots in the nasal passages of sheep and goats, bots in the stomach of horses, and cattle grubs or warbles in the spinal canal, back, or esophageal tissues.

Many ectoparasite infestations are seasonal and predictable and can be countered by prophylactic use of ectoparasiticides. For example, in temperate countries flies are seen predominantly from late spring to early autumn, tick populations increase in the spring and autumn, and lice and mites during the autumn and winter months. Treatments

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can therefore be targeted at anticipated times of peak activity as a means of limiting disease and parasite populations.

Most ectoparasiticides are neurotoxins, exerting their effect on the nervous system of the target parasite.

Those used in large animals can be grouped according to structure and modes of action into the organochlorines, organophosphates and carbamates, pyrethrins and pyrethroids, avermectins and milbemycins, formamidines, insect growth regulators, and a number of miscellaneous compounds, including synergists (eg, piperonyl butoxide).

There are also a number of useful compounds that have repellent activity rather than insecticidal activity, including MGK-264, butoxypolypropylene-glycol, and DEET

ECTOPARASITICIDES

Forms/Formulations: Sprays, Dips, Pour-ons, Shampoos, Dusts or powders, Foggers Oral products, Spot-ons, Injectables, Granules, Jetting, Sponge on, Collars

Classification: A. Based on Mode of action/ mode of entry Into the Insect

Stomach – Ingested & kill by action on or absorption into digestive system Contact -– Absorbed through body wall. Must come into direct contact with insect to kill.

Fumigant- – Enter tracheal system in form of a gas Systemic-oral route or injections

B. Based on Chemical structure Organochlorines (OCC). Eg: lindane, DDT Organophosphates(OPC) Eg: malathion, coumaphos Carbamates eg: carbaryl Botanicals

- Pyrethrins and pyrethroids eg: cypermethrin , allethrin- Rotenone - D-limenone and linalool

Macrocyclic lactones. Eg; avermectins and milbemycins Formamidines – eg: amitraz Insect growth regulators (IGR)Eg: Cyromazine, Pyriproxyfen Insect development inhibitors. (IDI) Eg: Lufenuron Neonicotinoid eg: Imidacloprid Synergists eg: piperonyl butoxide Repellents eg: DEET( N,N-Diethyl –m -toluamide), stabilene Pyrazoles. Eg: Fipronil Spinosyns. Eg: Spinosad

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Semicarbazone eg: metaflumizone Miscellaneous eg: lime sulfur, benzyl benzoate

1. ORGANOCHLORINES/CHLORINATED HYDROCARBONS

Examples: Aldrin, DDT, Dieldrin, Methoxychlor, chlordane, DDD, endrin, heptachlor, gamma benzene hexa chloride (lindane) Old-fashioned insecticides , have been withdrawn in many parts of the world

due to concerns regarding environmental persistence some compounds, including lindane (γ benzene hexachloride) and

methoxychlor, are still used for topical application and have excellent activity and apparent safety.

Highly persistent,, heavily chlorinated Very lipophilic, accumulating iin ffats Very toxic to aquatic species Chronic toxicity problems,, especially I in birds, mammals most chlorinated hydrocarbons are banned because these insecticides persisted

in the environment and increased in the fatty tissues of animals; as not being easily biodegraded .

Many insect populations developed resistance to these insecticides. Toxicity : CNS signs, convulsions can be treated by anticonvulsants like

phenytoin

Organochlorines fall into 3 main groups:

1) chlorinated ethane derivatives such as DDT (dichlorodiphenyltrichloroethane), DDE (dichlorodiphenyldichloroethane), and DDD (dicofol, methoxychlor); 2) cyclodienes, including chlordane, aldrin, dieldrin, hepatochlor, endrin, and tozaphene; 3) hexachlorocyclohexanes such as benzene hexachloride (BHC), which includes the g-isomer, lindane

Chlorinated ethanes cause inhibition of sodium conductance along sensory and motor nerve

fibers by holding sodium channels open, resulting in delayed repolarization of the axonal membrane. This state renders the nerve vulnerable to repetitive discharge from small stimuli that would normally cause an action potential in a fully repolarized neuron.

Cyclodienes appear to have at least 2 component modes of actioninhibition of γ-amino butyric acid (GABA)-stimulated Cl- flux and interference with Ca2+ flux. The resultant inhibitory postsynaptic potential leads to a state of partial depolarization of the postsynaptic membrane and vulnerability to repeated discharge. A similar mode of action has been

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reported for lindane, which binds to the picrotoxin side of GABA receptors, resulting in an inhibition of GABA-dependent Cl- flux into the neuron

Hexachlorocyclohexanes DDT and BHC were used extensively for flystrike control but were

subsequently replaced in many countries by more effective cyclodiene compounds, such as dieldrin and aldrin.

The development of resistance, as well as environmental concerns, have largely led to their withdrawal. DDT and lindane were widely used in dip formulations for the control of sheep scab, but the organophosphates and subsequently the synthetic pyrethroids have mostly replaced them

2. ORGANOPHOSPHATES

Examples: Chlorpyrifos , Diazinon, Malathion , Phorate, Terbufos, Parathion, Sumithion, Dichlorovos, Coumaphos, Diazinon, Bromecyclan, Dioxthion famphur, fenthion, trichlorfon, stirofos, phosmet, and propetamphos

Generally more toxic to vertebrates than the chlorinated hydrocarbons, but they tend to be less persistent in the environment.

The organophosphates comprise a large group, many of which are available for topical application and in ear tags as well as for premise control of parasites. There have been many products available worldwide for use in domestic animals, although only a few of the available compounds continue to be used for on-animal treatment

Organophosphates are neutral esters of phosphoric acid or its thio analog that inhibit the action of acetylcholinesterase (AChE) at cholinergic synapses and at muscle endplates. The compound mimics the structure of acetylcholine (ACh); when it binds to AChE it causes transphosphorylation of the enzyme

All organophosphates are derived from one of the phosphorus acids. OP

chemical structures are similar to the "nerve gases“ & their modes of action are also similar

The OPs work by irreversibly inhibiting the vital enzyme cholinesterase (ChE). Inhibition results in the accumulation of acetylcholine (ACh) at the neuron/neuron and neuron/muscle (neuromuscular) junctions or synapses, causing rapid twitching of voluntary muscles and finally paralysis (knock down effect) .

Organophosphates can be extremely toxic in animals and humans, causing an inhibition of AChE and other cholinesterases. Chronic toxicity results from inhibition of the enzyme neurotoxic esterase and is associated with particular compounds

Toxicity: cholinergic signs can be treated by atropine and cholinesterase re activator 2-PAM

3. CARBAMATES

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Egs: Aldicarb , Carbaryl, Propoxur, Carbofuran

are derivatives of carbamic acid Inhibits the vital enzyme cholinesterase (ChE) reversibly This inhibition results

in the accumulation of acetylcholine (ACh) at the neuron/neuron and neuron/muscle (neuromuscular) junctions or synapses and causes rapid twitching of voluntary muscles and finally paralysis.

Thery are closely related to organophosphates and are anticholinesterases. Unlike organophosphates, they appear to cause a spontaneously reversible block on AChE without changing it.

It has low mammalian toxicity but may be carcinogenic and is often combined with other active ingredients

4. BOTANICALS: Derived from flower, leaves , stemms, roots of plants Used as ectoparasiticidals or repellants

a. PYRETHRINS AND SYNTHETIC PYRETHROIDS

Egs: Tefluthrin , Lambda cyalothrin , Cyfluthrin, Deltamethrin, flumethrin, cis-cypermethrin, Allethrin, permethrin , bioallethrin, , , fenvalerate, flumethrin, , phenothrin, zetamethrin, Resmethrin, alpha cyalothrin, Cyfluthrin

Natural pyrethrins are derived from pyrethrum, a mixture of alkaloids from the chrysanthemum cinerariaefolium plant.

Pyrethrum extract, prepared from pyrethrum flower, contains ~25% pyrethrins Synthetic pyrethroids are synthesized chemicals modeled on the natural

pyrethrin molecule. They are more stable and have a higher potency than natural pyrethrins

Like the botanical pyrethrum, synthetic pyrethroids have fast Knock down activity against flying insects and low mammalian toxicity

The pyrethrins and pyrethroids are lipophilic molecules that generally undergo rapid absorption, distribution, and excretion.

They provide excellent knockdown (rapid kill) but have poor residual activity due to instability.

Pyrethrin I is the most active ingredient for kill, and pyrethrin II for rapid insect knockdown

The mode of action of pyrethrins and synthetic pyrethroids( resembles that of DDT) is by interfering with sodium channels of the parasite nerve axons, resulting in delayed repolarization and eventual paralysis.

Synthetic pyrethroids can be divided into 2 groups (types I and II, depending on the presence or absence of an α-cyano moiety).

Type I compounds have a mode of action (similar to that of DDT) that involves interference with the axonal Na+ gate leading to delayed repolarization and repetitive discharge of the nerve.

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Type II compounds also act on the Na+ gate but do so without causing repetitive discharge. The lethal activity of pyrethroids seems to involve action on both peripheral and central neurons, while the knockdown effect is probably produced by peripheral neuronal effects only.

b. ROTENONE Derris elliptica source Respiratory poison oin insects, inhibit NADH oxidation and ATP formation Active ingredient in ear drops and dips for flea, tick, lice, mite control in dogs

and cats , formulated with pyrethrins or synergists Toxic to swine, fish, snakes

c. d-LIMONENE AND LINALOOL

Volatile oil from peel of orange and citrus fruit Vapours toxic to insects, toxic to cats Used in sprays , shampoos, dips for flea control They have insecticidal activity that can be enhanced when synergized with

piperonyl butoxide.

5. MACROCYCLIC LACTONES (AVERMECTINS and MILBEMYCINS)

Endectocidal activity, particularly against ectoparasites, is variable and depends on the active molecule, the product formulation, and the method of application

Macrocyclic lactones can be given PO, parenterally, or topically (as pour-ons). The method of application depends on the host and, to some degree, on the

target parasites. In cattle, eg, available endectocide products can be given PO, by injection, or topically using pour-on formulations.

The latter are generally more effective against lice ( Lignonathus , Haematopinus , and to some extent Bovicola ) and headfly ( Haematobia / Lyperosia ) infestations, when compared with equivalent compounds administered parenterally.

In sheep, PO administration of some endectocides has little effect against psoroptic mite infestations ( Psoroptes ovis ), but parenteral administration increases activity.

The route of administration and product formulation all influence rates of absorption, metabolism, excretion, and subsequent bioavailability and pharmacokinetics of individual compounds.

6. FORMAMIDINES Amitraz

is the only formamidine used as an ectoparasiticide, and has been

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widely used in cattle, sheep, goats , dogs and pigs. .It appears to act by inhibition of the enzyme monoamine oxidase and as

an agonist at octopamine receptors. (Octopaminergic Agonist) Monoamine oxidase metabolizes amine neurotransmitters in ticks and

mites, and octopamine is thought to modify tonic contractions in parasite muscles.

Amitraz is a synaptic ectoparasiticide and appears to mimic the action of the adrenaline-like neurotransmitter/ neurohormone octopamine, elevating cyclic-AMP in certain CNS neurons and peripheral tissues. This results in tremors and convulsions, as well as suppression of feeding and reproduction.

It is known to have a rapid knock down on the control of animal

ectoparasites, such as ticks and mites. The compound persists on hair and skin long enough to control all

stages of the parasite Amitraz has a relatively wide safety margin in mammals; the most

frequently associated side effects include sedation, which may be associated with an agonist activity of amitraz on α2 -receptors in mammalian species.

Amitraz is classified as a contact insecticide and hence does not require the tick to ingest the molecule for it to take effect.

Amitraz is broken down rapidly in soil with a half-life of less than 24 hours. Amitraz is available as a spray or dip for use against mites (Demodex),

lice, and ticks in domestic livestock.

7. INSECT GROWTH REGULATORS (IGR) AND INSECT DEVELOPMENT INHIBITORS. (IDI)

Insect growth regulators (IGR; juvenile hormone analogs or juvenoiods): Examples: Cyromazine, pyriproxyfen, methoprene, fluazuron, fenoxycarb

Insect development inhibitors. (IDI): Examples: Lufenuron, Diflubenzuron, Novaluron, flufenoxuron

They represent a relatively new category of insect control agents. They constitute a group of chemical compounds that do not kill the target parasite

directly, but interfere with growth and development. They act mainly on immature parasite stages and are not usually suitable for the

rapid control of established adult parasite populations. Where parasites show a clear seasonal pattern, insect growth regulators can be applied prior to any anticipated challenge as a preventive measure.

They are widely used for blowfly control in sheep but have limited use in other livestock

Based on their mode of action, insect growth regulators can be divided into

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- chitin synthesis inhibitors (benzoylphenyl ureas) - chitin inhibitors (triazine/pyrimidine derivatives) - juvenile hormone analogs.

Several benzoylphenyl ureas have been introduced for the control of ectoparasites., are classified as insect development inhibitors. (IDI) or chitin synthesis inhibitors

Chitin is a complex aminopolysaccharide and a major component of the insect’s

cuticle. During each molt, it has to be newly formed by polymerization of individual sugar molecules.

The exact mode of action of the benzoylphenyl ureas is not fully understood. They inhibit chitin synthesis but have no effect on the enzyme chitin synthetase.

It has been suggested that they interfere with the assembly of the chitin chains into microfibrils. When immature insect stages are exposed to these compounds, they are not able to complete ecdysis and die during molting.

Benzoylphenyl ureas also appear to have a transovarial effect. Exposed adult female insects produce eggs in which the compound is incorporated into the egg nutrient. Egg development proceeds normally, but the newly developed larvae are incapable of hatching.

Benzoylphenyl ureas show a broad spectrum of activity against insects but have relatively low efficacy against ticks and mites. The exception is fluazuron, which has greater activity against ticks and some mite species

Benzoylphenyl ureas are highly lipophilic molecules. When administered to the host, they build up in body fat, from which they are slowly released into the bloodstream and excreted largely unchanged.

Triazine and pyrimidine derivatives are closely related compounds that are also chitin inhibitors. They differ from the benzoylphenyl ureas both in chemical structure and mode of action, in that they appear to alter the deposition of chitin into the cuticle rather than its synthesis

Cyromazine, a triazine derivative, is effective against blowfly larvae on sheep and lambs and also against other Diptera such as houseflies and mosquitos. At recommended dose rates, cyromazine shows only limited activity against established strikes and must therefore be used preventively. Blowflies usually lay eggs on damp fleece of treated sheep. Although larvae are able to hatch, the young larvae immediately come into contact with cyromazine, which prevents the molt to second instars.

The juvenile hormone analogs mimic the activity of naturally occurring juvenile hormones and prevent metamorphosis to the adult stage. Once the larva is fully developed, enzymes within the insect’s circulatory system destroy endogenous juvenile hormones, prompting development to the adult stage. The juvenile hormone analogs bind to juvenile hormone receptor sites, but because they are structurally different, are not destroyed by insect esterases. As a consequence, metamorphosis and further development to the adult stage does not proceed.

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Methoprene is a terpenoid compound with very low mammalian toxicity that mimics a juvenile insect hormone and is used as a feed-through larvicide for hornfly ( Haematobia ) control on cattle.

Fenoxycarb , has greater stability in presence of UV light, and is not degraded by insect natural estrases unlike methoprene. They are ysually formulated in collar or spray with either pyrethroid (permethrin) or OPC (chloropyrifos) as an adulticide

Lufenuron, a benzoylphenyl urea, inhibits the formation of chitin (a polymer of N-acetyl glucosamine), which is a major component of insect exoskeletons.

During each larval molt, chitin is reformed by polymerization. Lufenuron interferes with polymerization and deposition of chitin, killing

developing larvae either within the egg or after hatching. Lufenuron is administered PO to dogs (once monthly at a dose of 10mg/kg ) or

cats ( 30mg/kg ) or by injection to cats. Female fleas feeding on treated animals are prevented from producing viable eggs

or larvae. Suppress the growth of adult fleas up to 32 days Other insect development inhibitors, such as diflubenzuron and cyromazine, also

have considerable activity against developing fleas. Insect growth regulators affect many insect species that undergo complete

metamorphosis, but have little or no activity against ticks or others which undergo incomplete metamorphosis

8. NEONICOTINOIDS (CHLORONICOTINYLS)

Examples: Acetamiprid , Clothianidin , Imidacloprid , Thiamethoxam, Nitenpyram

The nicotinoids are a new class of insecticides that are referred to as nitro-quanidines, neonicotinyls, neonicotinoids, chloronicotines, and recently as chloronicotinyls.

The nicotinoids are modeled after natural nicotine. Two compounds in this category are currently available for veterinary use—

imidacloprid and nitenpyram. Imidacloprid works by binding to postsynaptic nicotinic acetylcholine receptors

in insects. This inhibits cholinergic transmission, resulting in paralysis and death.

Imidacloprid is applied as a 10% spot-on topical product and is used primarily to control fleas on both dogs and cats. It also has excellent activity against lice.

While it has potent residual activity, swimming and repeated bathing may compromise its duration of activity.

Nitenpyram is administered PO in pill form to kill fleas in both dogs and cats. It is absorbed rapidly, with maximal blood concentrations reached within 1.2 hr and 0.6 hr in dogs and cats, respectively.

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Even though imidacloprid and nitenpyram are classified similarly, their mechanisms of action appear to be different. While imidacloprid is described as a paralytic, nitenpyram produces hyperexcitability in fleas prior to death

9. PYRAZOLES This group of compounds has broad-spectrum insecticidal and acaricidal activity. The only member of this group currently available for use is fipronil.

Fipronil

Systemic material with contact and stomach activity. Fipronil binds to γ-aminobutyric acid receptors of insects, inhibiting the flux of

Cl- ions into nerve cells, which results in hyperexcitability. similar to the action of the Cyclodienes

Fipronil is a broad-spectrum pesticide with activity against fleas, ticks, mites, and lice. This is a long-acting poison for dogs and cats.. It kills adult fleas, cockroaches and ants. It is the conventional barrier treatment for termites. Can be toxic to humans

Fipronil is absorbed and accumulates in the sebaceous glands, has very low solubility in water, and has prolonged residual activity on both dogs and cats

.It is also formulated as baits for cockroaches, ants and termites. Fipronil is effective against insects resistant or tolerant to pyrethroid,

organophosphate and carbamate insecticides.

10. SPINOSYNS Spinosad

Spinosad is a mixture of the two most active naturally occurring metabolites, spinosyn A and spinosyn D, produced by S. spinosa

is a fermentation metabolite of the actinomycete, Saccharopolyspora spinosa, a soil-inhabiting microorganism

It has both contact and stomach activity It must be ingested by the insect, therefore it has little effect on sucking insects

and non-target predatory insects. Spinosad works by contact and by ingestion. Contact occurs either by direct

application to the insect or by movement of the insect onto a treated surface. Ingestion occurs as insects feed on treated substrate (such as foliage).

Highly active by ingestion (5 times more effectivethan contact) and to a lesser degree by contact

It is relatively fast acting. The insect dies within 1 to 2 days after ingesting the active ingredient

Mode of action— The mode of action of spinosad (although not fully elucidated) is characterized by excitation of the insect nervous system, leading to involuntary muscle contractions, prostration with tremors, and paralysis.

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Spinosad acts by disrupting binding of acetylcholine in nicotinic acetylcholine receptors at the postsynaptic cell.

The unique mode of action, lack of cross resistance, selectivity that leaves predacious insects, and moderate residual profile result in a low probability of resistance development.

It degrades quickly in soil. It is toxic to bees, but not other beneficial insects Spinosad presents a favourable environmental profile. It does not leach,

bioaccumulate, volatilize, or persist in the environment. Spinosad will degrade photochemically when exposed to light after application. Because spinosad strongly adsorbs to soils, it does not leach through soil to groundwater when used

properly. The unique mode of action of spinosad, coupled with a high degree of activity on

targeted pests, low toxicity to non-target organisms (including many beneficial arthropods), and resistance management properties make spinosad an excellent new tool for integrated pest management

Spinosad should not be used in puppies under age 14 weeks and in pregnant or nursing females

It is available in 140 mg, 240 mg, 560 mg, 810 mg, and 1620 mg chewable tablets, given once a month to kill fleas in dogs only, at a dose rate of 30-60mg/kg .

11. SEMICARBAZONE

Metaflumizone Metaflumizone is a new pesticide in the flea control armory and is expected to be

quite effective. Metaflumizone is the first new small animal ectoparasitic compound, with a

different MoA, in over 10 years. Metaflumizone belongs to the semicarbazone group of compounds and is an

open-chain derivative designed to provide favourable toxicological and environmental profiles.

It is the first Sodium Channel Blocker Insecticide (SCBI) or Sodium Channel Antagonist in the animal health market. The molecule does not require the insect to metabolise it into its functional form and hence remains the only SCBI not requiring bio-activation

This had no previous use in animal health or agriculture. Therefore, it shows no incidence of resistance in veterinary or non-veterinary use. There is no cross resistance with other insecticides also

Metaflumizone is an axonal insecticide and works by affecting the ability of sodium to flow across the nerve cell membrane, a sodium channel blocker

When sodium is prevented from flowing into the axon interior correctly, the nerve impulse cannot be generated nor can it be carried down the nerve cell to the

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synapse. This ultimately results in a lack of coordination due to nerve dysfunction, then paralysis and finally the death of the insect n

Maximum efficacy is achieved within 48 hours. An has got up to 6 weeks residual efficacy against fleas. . Can be used as part of a treatment/control strategy for flea allergy dermatitis. .

Effective against both Ctenocephalides felis and Ctenocephalides cani Rapid and continued protection against ticks , Up to 4 weeks residual activity Metaflumizone is rapidly distributed throughout the surface of the body and do

not work through a systemic effect, so there is minimal chance of any drug interactions occuring. . Can be used in puppies from 8 weeks

Presently it is available as a clear, yellow to amber spot-on solution, in combination with amitraz (Each ml contains 150 mg metaflumizone and 150 mg amitraz) ; The recommended minimum dose is 20 mg/kg bodyweight for each of metaflumizone and amitraz, equivalent to 0.133ml/kg bodyweight

Contraindications,: -puppies under 8 weeks of age., sick or debilitated dogs or dogs suffering from heat stress. , pregnant and lactating animals. The current available veterinary medicinal product(Not available in India, presently) is for spot-on application only. Not to be administered orally or via any other route.

12. SYNERGISTS Synergists are generally not considered toxic or insecticidal, but are used with

insecticides to enhance their activity. They are used primarily to increase the effectiveness of pyrethrum or pyrethroids Synergists inhibit cytochrome P450-dependent monooxygenases or glutathione s-

transferases, enzymes produced by microsomes in insect tissues. They bind the oxidative enzymes and prevent them from degrading the toxicant.

Piperonyl butoxide and N-octyl bicycloheptene dicarboxamide(MGK264) are the common synergists

Piperonyl butoxide is a methylenedioxyphenyl compound that has been widely used as a synergistic additive in the control of arthropod pests.

It is commonly used as a synergist with natural pyrethrins. The degree of potentiation of insecticidal activity is related to the ratio of

components in the mixture; as the proportion of piperonyl butoxide increases, the amount of natural pyrethrins required to evoke the same level of kill decreases.

The insecticidal activity of other pyrethroids, particularly of knockdown agents, can also be enhanced by the addition of piperonyl butoxide.

The enhancement of activity of synthetic pyrethroids is normally less dramatic. Piperonyl butoxide inhibits the microsomal enzyme system of some arthropods and is effective against some mites. In addition to having low mammalian toxicity and a long record of safety, it rapidly degrades in the environment

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13. REPELLENTS

are added to formulations of exctoparasiticides to induce ectoparsites move away/ repel from trated animals

Popular in humans as mosquito and fly repellant products Various products from natural sources, as well as synthetic compounds, have

been used as insect repellents. Such compounds include cinerins, pyrethrins and jasmolins citronella, indalone, garlic oil, MGK-264 butoxypolypropylene-glycol, DEET, and DMP (dimethylphthalate).

The use of repellents is advantageous as legislative and regulatory authorities become more restrictive toward the use of conventional pesticides. They are used mainly to protect horses against blood-sucking arthropods, particularly midges ( Culicoides)

N,N-diethyl-3-methylbenzamide (DEET, previously called N,N-diethyl-meta-toluamide) remains the most effective among currently available insect repellents for humans. Others- butoxypolypropylene glycol(stabilene) It is a broad-spectrum repellent that is effective against mosquitos, biting flies,

chiggers, fleas, and ticks. However, the effectiveness of DEET formulations for dogs and cats has not been

proved, and concentrated formulations containing DEET have caused weakness, paralysis, liver disease, and seizures in pets.

The synthetic pyrethroid permethrin, while not a true repellant, is a rapidly acting contact insecticide that affects arthropod nervous systems. This leads to death or “knockdown,” thereby producing a repellent-like activity against fleas, ticks, and mosquitoes.

14. BORATE CONTAINING COMPOUNDS Compounds containing Sodium borate, boric acid powders Used for indoor premise applications Mode of action is by dessication Demonstrable effect on ova and larvae development Longetivity, low toxicity, stability , odourless, extended effectiveness

15. MINERAL INSECTICIDES Silica gel and diatomaceous earth Mode of action is by dessication Adulticide, Moderate residual action with low toxicity, used especially in the

environment BIOLOGICAL FLEA CONTROL

Focussed on environmental control of fleas Steinernema carpocapsae, a nematode which feeds on flea larvae has been

under investigation

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