1. Antiparasitics Chapter 12-3
Dr. Dipa Brahmbhatt VMD MpH

2. Objectives Terminology – antiparasitics MOA antiparasitics
Precautions of antiparisitics

3. Heartworm Prevention and Treatment

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: 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: mg/ kg OR Tramadol: 1mg/lb BID X 3 days PO before melarsomine injection;
DAY 31
Melarsormine: 0.1 mls/ kg IM

8. Dogs < 22 lb. = 1 inch needle 23G
Dogs > 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 > 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 1:10 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.

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: > 6 months - < 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

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” PNS 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. α1- adrenergic receptors – cause vasoconstriction of skin, GI tract, and kidney [don’t need to digest, make urine, or bleed profusely}
2. β1-adrenergic receptors - increase heart rate and force of contraction
3. β2-adrenergic receptors - cause bronchodilation (relaxation)

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 > HL ataxia > 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 > progress to shaking > ataxia > paralysis > 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
Adam’s 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 parasite’s 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) > decreases norepinephrine > sedation. Inhibits monoamine oxidase hence don’t 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 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)
Taktic®EC (cattle)
Available in collars, topical treatment, dip, or sponge-on bath.

38. MACROLIDES Milbemycin oxime Selamectin (Revolution): topical
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, don’t 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 <8 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

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 <3 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 flea’s 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
Bill, R.L. Clinical Pharmacology and Therapeutics for the Veterinary Technician, 3rd edition
Beale, Karin. Favorite New Treatment Options in Veterinary Dermatology. Gulf coast veterinary specialists symposium, 2012.