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Antiparasitics

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Title: Antiparasitics


1
Antiparasitics
  • Chapter 12-3

Dr. Dipa Brahmbhatt VMD MpHdbrahmbh_at_yahoo.com
2
Objectives
  • Terminology antiparasitics
  • MOA antiparasitics
  • Precautions of antiparisitics

3
Heartworm Prevention and Treatment
4
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5
Treatment of Heartworm Disease
  • Heartworm disease is caused by the filarial
    nematode Dirofilaria immitis
  • Three stages of management of heartworm disease
  • Adulticide therapy
  • Microfilaricides Eradication of circulating
    microfilariae after infection
  • Preventing third-stage larvae from reaching
    maturity (preventative)

6
Treatment of Heartworm Disease
  • Adulticide therapy
  • Melarsomine - Immiticide 1996
  • Given in the epaxial muscles BETWEEN L3 L5
  • Arsenic compound
  • Less toxic than former drug (Caparsolate -
    thiacetarsamide)
  • SE include coughing, gagging, and lethargy,
    pulmonary congestion, localized inflammation
    thromboembolism (fragments of worms) swelling and
    pain
  • Nephrotoxicity and hepatotoxicity have been
    reported.
  • Class 3 fatigue, dyspnea, right heart changes in
    radiograph, RHF slow kill
  • Class 4 Not recommended for animals with caval
    syndrome (large numbers of adult heartworms in
    the right ventricle, right atrium, and vena
    cava).

7
  • Heartworm Treatment Slow Kill Method VTI
  • Team Dr. B, Dr. Dev, Miss Kennar, Miss Foitnik
  • Doxycycline 5 10 mg/ kg (SID or BID)
  • Prednisone 1 mg/kg BID X 7 days SID X 7 days,
    EOD X 7 days 
  • DAY 1
  • Buprenex 0.015 mg/ kg OR Tramadol 1mg/lb BID X
    3 days PO before melarsomine injection
  • Famotidine 0.5 mg/kg SQ before melarsomine
    injection
  • Melarsormine 0.1 mls/ kg IM 
  • DAY 30
  • Buprenex 0.015 mg/ kg OR Tramadol 1mg/lb BID X
    3 days PO before melarsomine injection
  • Famotidine 0.5 mg/kg SQ before melarsomine
    injection
  • Melarsormine 0.1 mls/ kg IM 
  • DAY 31
  • Buprenex 0.015 mg/ kg OR Tramadol 1mg/lb BID X
    3 days PO before melarsomine injection
  • Famotidine 0.5 mg/kg SQ before melarsomine
    injection
  • Melarsormine 0.1 mls/ kg IM

8
Dogs lt 22 lb. 1 inch needle 23G Dogs gt 22 lb.
1.5 inch 22G
9
Treatment of Heartworm Disease
  • Adulticide therapy
  • LEVAMISOLE
  • Not effective Kills few adult heartworms
  • and neurological SE
  • May be used as inexpensive treatment for reducing
    adult burden and clearing mff. from blood
  • Ivermectin and Seleamectin has been shown to
    reduce adult burden when used over time
  • After adulticide treatment After 1-2 weeks 0r
    4-6 weeks
  • Worm emboli gt pulmonary inflammation coughing,
    fever, /- bloody cough (hemoptysis)
  • Cage rest, glucocorticoids, aspirin?? (not if
    hemoptysis)
  • Adulticide tx. Not recommended in cats

10
Treatment of Heartworm Disease
  • MICROFILARICIDES
  • Ivermectin (most common) 0.05 mg/kg
  • Given at higher dose as a microfilaricide
  • Monitor for neurologic side effects, anaphylactic
    shock
  • Should kill microfilaria in 3 weeks (monitor)
  • 1 ivomec 0.1 ml/ 20kg or dilute 110 and 1ml/
    20kg
  • Milbemycin oxime (interceptor/ sentinel/
    trifexis)
  • 0.5mg/kg. Use with caution in HW dogs
    Anaphylactic shock
  • Levamisole (infrequently used)
  • Given for 1 week or longer depending on dosage.
  • MOXIDECTIN IS NOT EFFECTIVE

11
Treatment of Heartworm Disease
  • PREVENTATIVES Preventing third-stage larvae from
    reaching maturity
  • Daily oral preventative
  • Diethylcarbamazine (DEC) Filaribits
  • Given during mosquito season and two months after
  • Anaphylactic shock and death can occur if given
    to dog with microfilaria
  • Filaribits Plus also controls ascarid infections
    (contains oxibendazole)

12
Preventatives - Macrolide
  • Ivermectin Heartgard, Iverhart PlusTM,
    Tri-Heart PlusTM
  • 0.006 mg/kg (very low for collies)
  • Macrocyclic lactones
  • Plus products also contain pyrantel pamoate
    (hooks, rounds)
  • Ages 6 months
  • Side effects include neurologic signs such as
    salivation, ataxia, and depression
  • Milbemycin oxime - Interceptor
  • Sentinel milbemycin oxime lufenuron
  • Also effective against hookworms, roundworms, and
    whipworms and Demodex mites in dogs.

13
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14
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15
Monthly Topical Preventatives
  • Selamectin - Revolution
  • Absorbed systemically
  • Dogs heartworm, adult fleas, ticks, ear mites,
    sarcoptic mange
  • Cats heartworm, adult fleas, ear mites,
    roundworms, hookworms

16
Monthly Topical Preventatives
  • Moxidectin imidacloprid Advantage Multi,
    Proheart 6
  • Heartworm prevention, Flea control, Intestinal
    parasite prevention
  • Children should not come in contact with
    application site within 30 minutes of
    administration
  • Do not use on sick, debilitated, or underweight
    animals

17
Parasite Preventatives in Dogs
18
Parasite Preventatives in Cats
19
Six-month Injectable Preventative
  • Moxidectin - Proheart
  • Side effects include neurologic and
    gastrointestinal signs
  • Withdrawn from the market in September 2004 due
    to increased reports of adverse side effects
    including liver and bleeding abnormalities.
  • Reformulated and reintroduced in 2008.
  • Owners must sign a special Informed Consent
    form
  • Age gt 6 months - lt 7 years
  • SE Anaphylaxis, V/D, lethargy,
  • erythma, pruiritis, hyperthermia
  • TX heartworm, Dilofilaria
  • Dimmitis, Ancylostoma caninum,
  • Uncinara stenocephalia

20
Ectoparasite Treatment
21
Ectoparasite Treatment
  • Ectoparasites can be controlled using a variety
    of different drugs in a variety of different
    formulations
  • Sprays, Dips, Pour-on, Shampoos, Dusts or
    powders, Foggers, Oral products, Spot-ons ,
    Injectables
  • Parasites Flies, grubs, lice livestock, flies
    (bots and maggots) horses, companion animals
    fleas, ticks, mange mites
  • Diseases Zoonotic Lyme, bubonic plague, RMSF

22
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24
Lifecycle Flea
25
Ectoparasite Treatment
  • Organophosphates and Carbamates
  • Pyrethrins and Pyrethroids
  • Amitraz
  • Macrolides
  • Imidacloprid
  • Fipronil
  • Nitenpyram
  • Insect Growth Regulators
  • Insect Repellents

26
Review - ANS
  • SNS Fight/Flight
  • Epinephrine and norepinephrine
  • Adnergic recoptors
  • Alpha 1 blood vessels skin, GI
  • Alpha 2 help regulate release of NE
  • Beta 1 HEART
  • Beta 2 SMOOTH MUSCLE blood vessels heart,
    skeletal muscle arterioles, terminal bronchioles
  • PNS
  • Acetylcholine
  • Cholinergic receptors
  • Muscarinic inc. GI stimulation, slow HR, miosis,
  • Nicotinic found both in PNS and SN

27
Neurotransmitters and Receptors
  • Smooth/Cardiac muscles may constrict or dilate in
    response to epi/norepi
  • 1. a1- adrenergic receptors cause
    vasoconstriction of skin, GI tract, and kidney
    dont need to digest, make urine, or bleed
    profusely
  • 2. ß1-adrenergic receptors - increase heart rate
    and force of contraction
  • 3. ß2-adrenergic receptors - cause
    bronchodilation (relaxation)

28
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29
Organophosphates Carbamates
  • MOA acetylcholinesterase inhibitor
  • Decompose readily in environment used more in
    agriculture
  • SLUDDE, bradycardia, and miosis (pinpoint
    pupils) classic signs of muscarinic/ nicotinic
    overstimulation
  • Delayed neurotoxicity syndrome has been reported
    in people, cats, dogs, and livestock occurs 1-2
    weeks
  • Metabolism OP toxic to myelin sheath gt HL ataxia
    gt paralysis
  • Cattle weakness, depression, droopy ears, bloat
  • TX Atropine (better for CNS X 10 dose of
    pre-anesthetic), Pralidoxime reverse OP - human
    pharmacies
  • Persian cats, sick cats, Whippets, Greyhounds,
    and certain exotic breeds of cattle are sensitive
    to Ops.
  • As a general rule, these insecticides should not
    be used on animals recovering from surgery, sick
    animals, pregnant animals, or animals considered
    to be stressed.

30
Organophosphates Carbamates
  • Ach muscarinic receptors
  • Toxicity
  • SLUDDE and miosis
  • Tx
  • X10 dose of atropine (better for CNS than
    glycopyrrolate)
  • Pralidoxime separates OP molecule from
    Ach-esterase
  • Ach nicotinic receptors
  • Toxicity
  • Progressive initially-tremors gt progress to
    shaking gt ataxia gt paralysis gt resp. failure

31
Glycopyrrolate (Robinul) and Atropine
Use Glycopyrrolate in Pregnant animals it does
not appreciably cross CNS or placenta
Atropine comes in Two concentration 0.5 mg/mL
(injectable-SA) and 2.0 mg/mL (injectable-LA)
32
Organophosphates Carbamates
  • Adams Flea and Tick Dip, Spray, and Tick Dust
  • Carbaryl (Mycodex shampoo with carbaryl)
  • Sevin Dust
  • Cythioate (Proban tablets and liquid)
  • Diazinon (Escort)
  • Phosmet (Paramite dip)

33
Pyrethrins and Pyrethroids
  • Pyrethrins are natural plant products, derived
    from chrysanthemum flowers
  • Largest group OTC, very safe, quick kill
  • Pyrethroids are synthetic pyrethrins better at
    killing, -thrin suffix
  • Resmethrin degraded by UV, leaves odor like
    stale urine
  • Fenvalerate and permethrin adhere to nylon/
    carpets reduces efficacy
  • Permethrin and deltamethrin Tick collars flea
    and ticks
  • allethrin, tetramethrin, deltamethrin,
    cyfluthrin,

34
Pyrethrins and Pyrethroids
  • MOA Acts on parasites nerve cell
  • membrane to disrupt sodium channel, which delays
    polarization and paralyzes the parasite
  • SE cats sensitive and can show neurological
    signs seizures/paralysis, poison fish
  • Synergists added piperonyl butoxide generally
    safe, neurotoxicity cats. Also add insect
    growth regulators (IGR)
  • Often manufactured with other products such as
    imidacloprid pyrethrin(Advantx not for cats)
    and as
  • synergist piperonyl butoxide
  • K9 Advantix, Bio-Spot for dogs

35
Formamidines Amitraz
  • One of the first effective agents available for
    demodectic mange in dogs. Can repel ticks.
  • MOA alpha 2 receptor agonist, adnergic (xylazine
    and detomidine) gt decreases norepinephrine gt
    sedation. Inhibits monoamine oxidase hence dont
    use with behavior modifying drugs
  • Toxic to cats and rabbits, Use protective
    clothing and gloves for humans keep it away from
    children use in a well-ventilated area
  • SE Animals may show sedation and incoordination
    for 24-48 hours after application, pruritus,
    hypothermia

36
Amitraz
  • Can be very toxic if ingested by animals or
    people
  • Reports of toxicity from ingestion of collars
  • Treated with supportive therapy and multiple
    doses of alpha-2 receptor antagonists Yohimbine
    (Yobine) or Atipamezole (Antisedan), Tolazoline
    (Priscoline, Tolazine)

37
Amitraz
  • ProMeris for dogs (synergistic with
    metaflumizone)
  • Mitaban Dip
  • PrevenTIC collar with
  • IGR for fleas pyriproxyfen
  • (Nylar)
  • TakticEC (cattle)

Available in collars, topical treatment, dip, or
sponge-on bath.
38
MACROLIDES
  • Milbemycin oxime
  • 2002 otic prep. In cats MilbeMite Otedectes
    cynotis
  • Selamectin (Revolution) topical
  • Dogs and cats fleas, ear mites, hwp
  • Dogs sarcoptes mange, tick
  • Extra label use exotics and wildlife

39
Imidacloprid
  • Advantage (imidacloprid fleas) and K9 Advantx
    ( permethrin tick and mosquito, dont use in
    cats)
  • Chloronicotinyl nitroguanidine
  • MOA Insect neurotoxin blocks receptor site for
    Ach-nicotinic, thereby blocking transmission of
    the impulse across the synapse.
  • Marketed for use in both dogs and cats fleas
  • Poorly absorbed through skin and kills adult
    fleas on contact
  • Wide margin of safety (toxicity in fish is low)
  • Four week residual activity, topical back of neck

40
Fipronil
  • Frontline
  • Fipronil with methoprene (Frontline plus)
  • MOA Interferes with GABA receptors - chloride
    channels of insects (less chloride in neuron),
    which overstimulates their nervous system causing
    death
  • Safe for mammals because has low affinity for our
    GABA receptors
  • Adult fleas, ticks, and chewing lice (on
    contact) controls sarcoptic mange with repeated
    treatments.
  • Methoprene is an insect growth regulator, which
    makes Frontline plus effective against flea eggs
    and larvae.
  • Applied topically (absorbed in sebaceous glands)
    not absorbed systemically
  • Residual activity, even after bathing
  • Not for use in puppies or kittens lt8 weeks of
    age.

41
Fipronil
  • Also marketed as a measured-dose spray product
    that is applied at a dose of 3 ml/kg body weight.
  • Container is calibrated to administer precise
    amount of insecticide to allow accurate dosing.
  • Manufacturer claims that fipronil is unlikely to
    produce toxicity even if consumed orally.
  • Fipronil binds with the dermis, hair follicles,
    and sebaceous glands.
  • Has alcohol salivation if licked and has
    unpleasant order

42
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43
Nitenpyram
  • Capstar
  • MOA Binds and inhibits Ach-nicotinic receptors
  • Safe for mammals low affinity for receptor (safer
    than OP)
  • Tablet begins to kill adult fleas within 30
    minutes
  • At least 90 fleas killed in 4 hrs. (dogs) 6
    hrs. (cats)
  • Can safely give a dose as often as one per day
  • Can use on puppies and kittens older than 4 weeks
    and weighing more than 2 lb.
  • Only kills adult fleas should also give insect
    growth regulator (IGR) to control fleas.
  • SE intense pruritus for short period THIS IS OK

44
Lindane
  • The only chlorinated hydrocarbon currently
  • used in veterinary medicine today.
  • Incorporated in some dog shampoos.
  • Kills insects on contact directly absorbed into
    insects and their eggs also a stomach poison for
    insects
  • Can produce harmful side effects in people and
    pets if absorbed in sufficient quantities.
  • Owners should wear gloves, apron, boots
  • Dispose of empty bottles and bath water according
    to EPA policies
  • Lindane should never be used on cats, puppies lt3
    weeks, lactating animals, or food animals.

45
Newer products
  • Spinosad (thanks bacteria) Bad taste
  • Comfortis and Trifexxis
  • MOA nerve paralysis of fleas at nicotinic Ach
    receptors and also GABA
  • Kills adult fleas 100 - 4 hrs
  • FAD
  • SE vomiting
  • To avoid split dose BID

46
Insect Growth Regulators
  • Insect growth regulators are compounds that
    affect immature stages of insects and prevent
    maturation to adults.
  • Include Insect development inhibitors (IDI) and
    juvenile hormone mimics (JHM)
  • Insect development inhibitors interfere with
    development of chitin, which is essential for
    proper egg formation and development of the
    larval exoskeleton. The egg-tooth used by flea
    larvae to exit egg is also made of chitin.

47
Insect Growth Regulators
  • Juvenile hormone mimics prevent fleas from
    molting to the next stage by interrupting normal
    molting process. (Fleas need low levels of JH to
    molt to the next stage these products mimic the
    fleas natural JH) The insect stays in the larval
    stage and eventually dies.
  • Insect growth regulators do not affect adult
    fleas.
  • Lufenuron (PROGRAM), methoprene, fenoxycarb, and
    pyriproxyfen are all IGRs.

48
Lufenuron
  • Program Insect Development Inhibitor
  • The flea component in Sentinel
  • Interferes with chitin synthesis in flea
    development
  • Given orally to dogs orally or SQ to cats lasts
    for 6 months
  • Fleas must bite the animal to be exposed to the
    drug.
  • Effects are noted in 2 weeks hence use with
    adulticide
  • Also investigated to use for ringworm
  • Lufenuron is distributed to fat and then leaches
    slowly back into the body fluids, providing a
    long duration of activity therefore drug needs
    to be given only once monthly.
  • SE vomiting, listlessness

49
Other IGRs
  • Methoprene (Ovitrol) is generally regarded as
    safe. It is found (sometimes as Precor) in
    sprays, topical products, and flea collars.
  • Female flea absorbs compounds from skin of animal
    (deposited by flea collar) and it is incorporated
    into eggs
  • Flea pupae in carpet are protected from
    methoprene because it binds to fibers in carpet.
  • FRONTLINE plus with fipronil
  • Pyriproxyfen (Nylar) JHM - Mostly used in
    environmental flea control products may have
    some activity against adult fleas (but not
    immediate) more potent than methoprene and
    fenoxycarb
  • Fenoxycarb was voluntarily withdrawn from the
    market by the manufacturer in 1996 because of
    concerns over the results of government testing
    involving the use of high doses. It breaks down
    to formaldehyde, a carcinogen.

50
Insect Repellents
  • Used to repel insects and keep them off of
    animals
  • Livestock, horses, outdoor dogs upright ears
    German Shepherds and Dobermans
  • May be used in combination with pyrethrins and
    pyrethroids
  • Include sprays, ear tags, and topicals for ear
    tips
  • Some products are insecticides as well as
    repellents
  • Control mosquitoes, flies, and gnats.
  • DEET Diethyltolamide (Blockade - Hartz)
    Combination with fenvalerate was withdrawn from
    market for several months because of reports that
    it caused death in several cats and dogs.
  • Signs of DEET toxicosis include excitation,
    tremors, seizures, ataxia, and vomiting.

51
Insect Repellents
  • Butoxypropylene glycol (Butox PPG or VIP Fly
    Repellent)
  • Used in equine fly repellents because it provides
    a shine that is of cosmetic value in show animals
  • Incorporated into flea and tick spray products
    for use in dogs and cats
  • Can cause dermal irritation if a harness or
    collar is applied over the area while the
    haircoat is still wet with spray.

52
Other External Antiparasitics
  • Rotenone - A.k.a. Derris Powder (derived from
    derris root)
  • Ear Miticide, Mitaplex-R
  • Used in dips and pour-on liquids
  • Toxic to fish and swine consider runoff
    possibilities when using.
  • D-limonene (VIP Flea Dip and Shampoo)
  • Derived from citrus peels
  • Has slight insecticidal activity
  • Pleasant smell provides quick kill may be used
    with other products

53
References
  • Romich, J.A. Pharmacology for Veterinary
    Technicians, 2nd edition. 2010.
  • Bill, R.L. Clinical Pharmacology and Therapeutics
    for the Veterinary Technician, 3rd edition. 2006.
  • Beale, Karin. Favorite New Treatment Options in
    Veterinary Dermatology. Gulf coast veterinary
    specialists symposium, 2012.
  • http//en.wikipedia.org/wiki/FileAdrenoceptor-Sig
    nal_transduktion.PNG
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