General aspects of ectoparasiticides

Uses

Animals to control cattle grubs, fleas, lice, mites, ticks, flies

Environment to kill fleas, flies, mosquitos, cockroaches

PO to kill adult fleas (nitenpyram), larvae and eggs (lufenuron), fly larvae (cyromazine, diflubenzuron, tetrachlorvinphos)

General aspects of ectoparasiticides

Trend

pour-on

spot-on

Must be properly applied to minimize injury

Dermal absorption in animals-lipophilic

weak/young animals differ in response-toxicity

Read labels and consider safety issues

most are highly lipid soluble->CNS disturbances

Anti-ChE poisoning: SLUDD

Avoid hot and humid weather

Species specific toxicity of ectoparasiticides

Horses

sensitive skin

easy to have urticaria

hyperemia

Species specific toxicity of ectoparasiticides

Ruminants

Have ~50% of ChE of other species

Avoid anti-ChE

Species specific toxicity of ectoparasiticides

Cats

easy to get excited

drug metabolism problem

grooming

Sensitive to synthetic pyrethroids and Anti-ChE

Ectoparasiticide formulations

Topical applications

Have great impacts on efficacy, persistency, toxicity

Sprays, dips, shampoos-water suspension (do above 40F/4C)

Pour-ons, spot-ons, dusts: can do <40F (4C) avoid extra moisture

Oil sprays: large animals, compressor to help-on hair coat, not skin (rare)

Ectoparasiticide formulations

in feed or oral

Systemic toxicity more likely

treat to avoid in practice

very safe insecticides used this way

cyromazine, lufenuron, diflubenzuron, nitenpyram, spinosad, tetrachlorvinphos (OP)

Examples of Anti-Cholinesterase agents

Organophosphates 

Carbamates (carbaryl, propoxur)

Can kill ticks and mites-acaricides

Cyromazine

Methoprene 

Pyriproxyfen

Lufenuron (Program)

Diflubenzuron (Dimilin, Equitrol II)

Pyrethroids

Rotenone

Acaricide-can kill mites and ticks

Ivermectin

Acaricide-can kill mites and ticks

Amiztraz

(Mitaban, Taktic, ProMeris Duo)

Acaricide-can kill mites and ticks

Imidacloprid (Advantage)

Dinotefuran (Vectra 3D)

Nitenpyram (Capstar)

Spinosad (Comfortis)

Fipronil (Frontline)

Acaricide-can kill mites and ticks

Organophosphates

general aspects

can kill all arthropods

withdrawal of chlorinated hydrocarbons->increased Anti-ChE importance

On the way out

Very toxic in ruminants and cats

No residue problems->serious toxicity

Organophosphates

Toxicity problems

SLUDD

cardiac arrhythmias

fasciculations

ataxia

convulsions

Chronic: paralysis, rare, TOCP (tri-o-cresyl phosphate)

Atropine sulfate: 0.2-0.4 mg/kg

1/4 dose IV, 3/4 dose SC, or to effect

in severe cases repeat every 3-4 h

Do not over-treat!!!

AChE reactivator pralidoxime (2-PAM)

Decontamination, supportive therapy

don't cross BBB

use within 24 hours of exposure to OP

Must use with atropine

Avoid drugs that affect ACh receptors and CNS

No cholinergic agonists

No skeletal muscle relaxants

No CNS stimulants, depressants

Organophosphates

insecticides

over 5,000 compounds

Thio compounds (stink)

Oxy compounds

Organophosphates

Thio compounds (stink)

Have to be metabolized to oxy- to be effective

coumaphos

chlorpyrifos

*diazinon*

ethion

famphur

fenthion

malathion

phosmet

pirimiphos

Organophosphates

oxy compounds

dichlorvos

tetrachlorvinphos

Carbamates

Inhibit AChE by forming non-covalent bond

Used in flea and tick control

Carbaryl (Sevin)

Propoxur (flea and tick collars)

Signs of intoxication

Treatment of overdose-atropine

Don't use 2-PAM for overdose

0.5-8 mos

each female lays 15-20 eggs/day

hatch in 2-14 days

larvae take 2 wk-6 months (3 moltings)->pupae (in cocoon)

Pupae take 5-14 days to become adults (but can stay for 1 yr)

Insect growth regulators

(Juvenile Hormone Analogs)

MOA

They mimic insect juvenile hormone to prevent molting

results in persistence of larva stage of insects

Insect growth regulators

Products

Cyromazine (Larvadex)

Methoprene (Precor, Ovitrol, Siphotrol, Frontline Plus)

Pyriproxyfen (Knockout Area Treatment, Vectra 3D)

Insect growth regulators

Toxicity

Insect Development Inhibitors (IDI's)

MOA

inhibition of chitin synthesis in larvae and egg tooth

no effects on adult insects

Insect Development Inhibitors (IDI's)

Products

Diflubenzuron (Dimilin, Equitrol II)

Lufenuron (Program)

Insect Development Inhibitors (IDI's)

Diflubenzuron

lipophilic

PO in horses (0.15 mg/kg/d) for fly control

feed from early spring to fall

no side effects

Insect Development Inhibitors (IDI's)

Lufenuron

Control fleas by PO or SC in dogs and cats, 6 wks or older

No effects on adult fleas

use in combo with an adulticide

PO 1x/month in dogs (10 mg/kg) after meal

PO 1x/month in cats (30 mg/kg) after meal

SC in cats (10 mg/kg/6 months)

Vomiting, anorexia, lethargy

Rotenone

Pyrethroids

Rotenone

MOA

Alkaloid to cause knockdown of arthropods

cleans garbage fish in ponds and lakes

Knockdown action due to inhibition of e- transport

(NADH->NAD⁺ +H⁺+2e-)

Rotenone

uses

in dogs and cats

control fleas, ticks, lice, mites

(Ear Miticide, Goodwinol Ointment)

Rotenone

effects

decreased cell respiration

decreased oxidation of lactate, glutamate

Rotenone

Toxicity

safe in animals

skin irritations and CNS disturbances (rare)

Do not use in reptiles

Pyrethroids

general

pyrethrins are alkaloids of pyrethrum flowers

cause knockdown of arthropods

Piperonyl butoxide

cyfluthri

cypermethrin

fenvalerate

deltamethrin

plambdacyhalothrin

permethrin

resmethrin

MGK 264-synergists

inhibitors of microsomal enzymes

tick and flea collar for dogs

6 months

Pyrethroids

MOA

Persistant opening of Na+ channels of neurons or muscle cells in arthropods

increased Na+ in cells

Depolarized membrane

Pyrethroids

Toxicity

local irritation

allergic dermatitis

hypersalivation and GI disturbances

CNS disturbances-esp in cats

arrhythmias-rare

Overdose can still cause fatality

Synthetic pyrethroid spot-on toxicity in dogs and cats

45-65% spot-ons for dogs

Contraindicated in epileptic dogs

Cats-very sensitive to them-even secondary exposure

Signs: tremors, rigidity, ataxia, seizures, hypersalivation, mydriasis

Central muscle relaxants

Ex: methocarbamol (Robaxin-V) 55-220 mg/kg IV

Similar to guaifenesin

Anticonvulsants

ex: diazepam

Macrocyclic lactones

(Macrolide endectocides)

General aspects

effective vs. grubs, mites, lice, ticks, flies

most of them do not kill fleas at clinical doses

do not kill arthropods promptly

interrupt feeding and laying of eggs

Macrocyclic lactones

For demodicosis

Ivermectin, 0.4-0.6 mg/kg/d, PO, 2-3 months

MDR1 gene (P-glycoprotein) test: done by WSU and SOLVO

start with 0.05 mg/kg/d

many normal dogs have a few mites

immunodeficient/hypothyroidism have clinical dz

transmitted by contact: from bitch to pups

spends entire life in follicles and sebaceous gland

females lay eggs in follicles

larvae->nymphs->adults

Mitaban

ProMeris Duo

Preventic collar

Taktic

Point-Guard

Amitraz

uses

mites

ticks

demodicosis (Mitaban)

-amitraz suspension dip on weekly bases

Amitraz

MOA

Amitraz

adverse reaction

CNS depression, bradycardia

due to activation of alpha2-adrenergic receptors

treatment with alpha2-antagonist

Amitraz

contraindications

don't use in weak, debilitated animals

don't use in horses

Nicotinic receptor agonist

Fleacide

Neonicotinoids: Imidacloprid, Nitenpyram, Dinotefuran

Spinosad

highly sensitive for insect receptors

No drugs resistance problems yet

Dinotefuran: inhibitory concentration: insects-900, vertebrates>100,00

Selectivity>111

Imidacloprid inhibitory concentration: insects-4.6, vertebrates 2600

Selectivity 565

*Nitenpyram: inhibitory concentration: insects-14, vertebrates 49000

selectivity 3500

-most selective for insects

-No adverse effects at recommended dosage regimens

-Safe in pregnant or nursing females

-Safe in conjunction with Heartworm preventatives, corticosteroids, antibiotics, antiparasitics

Imidacloprid (Advantage)

general

for dogs and cats 4 weeks or older

mature fleas die in 12h (~100%)

fleacidal activity: 25% in 3 h; 95% in 8 hours

Imidacloprid

application

apply once a month:between scapulas (spot-on 5-10 mg/kg)

Shampooing doesn't wash out

Persistent for 30 days-stored in sebaceous gland

Advantage II: imidacloprid-pyriproxyfen (IGR)

K9 Advantix II: imidacloprid-pyriproxyfen-permethrin

Advantage Multi: imidacloprid-moxidectin

cyclic lactone

Dinotefuran (Vectra 3D)

application

spot-on

7-16 mg/kg

1x/month for dogs and cats 4 weeks or older

shampooing does not wash out

Dinotefuran

action and examples

Faster fleacidal than imidacloprid (8 hours)

killing 95% of fleas in 6 hours

dinotefuran-pyriproxyfen-permethrin for dogs

dinotefuran-pyriproxyfen for cats

Nitenpyram (Capstar)

Administration

1 mg/kg, PO after meal

labeled for dogs and cats 4 weeks or older

Fleacidal activity: killing 95% fleas in 5 hours

lasting only 1-2 days

Nitenpyram

Fate

differs from other neonicotinoids

dose after meal; rapid GI absorption

Hydroxylation, conjugation, urinary excretion

No accumulation in body tissues

Plasma t1/2: 3 h in dogs, 8 hours in cats

Nitenpyram

safety and toxicity

no adverse effects at 10 mg/kg for 2 weeks

safest fleacide with shortest duration

can be used in newborn animals

Nitenpyram

combination

Spinosad (Comfortis)

general aspects

A macrocyclic lactone

isolated from Saccharopolyspora spinosa

Spinosad

Adminstration

1x/month, PO, 30 mg/kg, after meal dosing

Good absorption with food

Spinosad

MOA

The binding sites on nicotinic receptor differ from other neonicotinoids

Dalpha6-subunits for spinosad: Da1-,Da2-, Da3- subunits for neonicotinoids (D=Drosophila)

Spinosad also activates glutamate-gate Cl- channels

Spinosad

metabolism

metabolized in liver

(demethylation/conjugation with glutathione)

excreted into urine

Plasma t1/2= ~10 days

Drug interaction

Ivermectin and Spinosad

both of them are macrocyclic lactones (Avermectins)

Dogs on large doses of ivermectin show more adverse effects when given spinosad

Do not use spinosad and macrocyclic lactone concurrently

Chloride channel blocker

Fipronil

application

topical in dogs >8 wk

topical incats>12 wk

6.5-13 mg/kg topically

spray and a spot-on

every 4 wks

store in sebaceous glands and follicles-slow release

shampooing doesn't wash out (wait 2 days post-application)

Fipronil

MOA

toxicity

Closes Cl- channels of arthropods

Safe, local irritation, hypersalivation

Frontline: effective vs. fleas and ticks 1 month

Frontline plus: has methoprene, effective vs. fleas for 3 months, against ticks 1 month

safe fleacide for topical use in cats/dogs >8wks

ProMeris duo-dog product, amitraz for ticks

spot-on 1x/month, last 2 months

MOA:Na+ channel blocker insect neurons

Adverse effects: lethargy, ataxia

>500 species are resistant to many

40% are animal pests

Behavioral and physiological mechanisms

gene mutation

1. decreased penetration or increase efflux of ectoparaciticide glycoprotein

2. increased breakdown of ectoparaciticide enzymes

3. Altered target proteins of ectoparaciticide

Ex: receptor AChE, ion channels

pyrethroids

neonicotinoids, ex: imidacloprid

propoxur has been proposed

IGR's, IDI's

Dust or sprat

Pyrethroids to cats