Ectoparasiticides Flashcards
Fipronil
Drug class: phenylpyrazole
Fipronil:
pharmacodynamics
MOA: GABA receptor antagonist
- Binds to the y-aminobutryric acid receptors of insects
- inhibits the influx of Cl- ions into the nerve cell
- Resulting in hyperexcitability of the insect nervous system
- May also bind to and block glutamate-activated chloride channels
- In mammals, fipronil binding ot the GABA receptor is less effective → accounts for its wide margin of safety
Fipronil:
Pharmacokinetics
topical application: translocation of the chemical over the entire body with significant deposition in sebum, sebaceous glands, and hair follicles
Minimal systemic absorption
Fipronil:
safety
wide margin of safety
extralabel use in young or small rabbits can cause seizures and death
Fipronil:
Usage
Dogs and Cats: topical - fleas, ticks, chewing lice
Available in combination with IGRs to kill juvenile stages of fleas
Insect Growth Regulators (IGRs)
juvenile-hormone analogs and insect development inhibitors
Harmless to the pet, livestock, and humans
Affect the developing stages of arthropods but not the adult ectoparasites
Juvenile-hormone analogs
methoprene, pyriproxifen
Juvenile-hormone analogs
Pharmacodynamics
MOA: mimic insect juvenile hormones
- In the normally developing insect, the hormone levels usually decrease prior to the adult stage
- Falsely signal arthropod to remain in its immature egg or larval stage and not develop to adult stage
Juvenile-hormone analogs
usage
available in combination with several groups of ectoparasiticides
Insect development inhibitors
Diflubenzuron, iufenuron
Insect development inhibitors
Pharamcodynamics
MOA: chitin synthesis inhibitors
- Interfere with the development of the insect exoskeleton by inhibiting chitn synthesis or deposition pathways
- Chitin is an essential constituent of flea eggshells and exoskeleton of immature fleas
Insect development Inhibitors:
usage
Diflubenzuron: feed-through fly control
Lufenuron: ingested by adult flea, is deposited in egg and prevents hatching
Imidacloprid, Dinotefuran, Nitenpyram
Drug class: neonicotinoids
Imidacloprid, Dinotefuran, Nitenpyram
Pharmacodynamics
MOA: Ach receptor agonist
- Modeled after natural nicotine and are acetylcholine mimics
- Binding irreversibly to postynaptic nicotinic acetylcholine receptors in insects causing the post-synaptic Na+ channels to remain continuously open
- Causes overstimulation of the nervous system, producing spontaneous muscular contractions followed by hyper-depolarization leading to paralysis and death
Imidacloprid, Dinotefuran
pharmacokinetics
Topical - no significant dermal absorption into blood → surface translocation → whole-body coverage
Imidacloprid, Dinotefuran
safety / toxicity
Imidacloprid: Typically safe
Dinotefuran: skin irritation
Imidacloprid, Dinotefuran
Usage of imidacloprid
spot on, collar: control fleas in dogs and cats
Combined with permethrin, flumethrin, pyriproxyfen, moxidectin
Imidacloprid, Dinotefuran
usage of dinotefuran
Spot on: efficacy against fleas
Dog formulation has permethrin
Do not use combination product in cats
Nitenpyram
Pharmacokinetics
Readily absorbed int he GI tract
Fleas begin falling off the coat of dogs and cats within 30 minutes
Nitenpyram
Saftey / toxicity
very safe
Transient itching period observed within 1-2 hours after treatment
Nitenpyram
Usage
dogs and cats, can be used daily
Spinosad
Drug class: spinosyn
Spinosad:
pharmacodynamics
MOA: Ach receptor agonist
- Binds to nicotinic acetylcholine receptors on post synaptic membranes of the insect nervous system
- But these are distinct form receptors affected by other neonicotinoids
- Limits the possibilitiy for cross-resistance with similar related insecticides
- Kills insects via hyperexcitation of the insect nervous system
Spinosad:
Pharmacokinetics
Oral: quickly absorbed to blood
starts to kill fleas within 30 minutes of admin
Better bioavailability when administered with food
Spinosad:
Safety / toxicity
Adverse reactions are rare; vomiting possible
Drug-Drug interactions between spinosad and ivermectin
Spinosad:
Usage
Dogs and cats: fleas
Isoxazolines
Afloxalaner, Fluralaner, Sarolaner, Lotilaner
Isoxazolines:
Pharamcodynamics
MOA: GABA receptor antagonist
- non-competitve GABA receptor antagonist
- Much more selective for GABA receptors in insects or ticks, than for those in mammals
- Bind to Cl- channels and block influx of Cl-
- Resulting in initial hyperexcitability of the insect nervous system, then paralysis and death
Isoxazoline:
Pharmacokinetics
High oral bioavailability, widely distributed in body
Half-life is long in dogs
Fleas exposed following attachement and feeding - onset of effect can occur within 8 hours of attachment
For ticks: onset of death is within 48 hours of attachment
Isoxazolines
safety / toxicity
safe.
very selective for fleas and tick nervous system compared to mammalian nervous system
Adverse effects: rare thus far. although vomiting, diarrhea, lethargy, and anorexia have been observed
IsoxazolinesL
Usage
Fleas and ticks
combination products are available
Macrocyclic lactones
endecticides
avermectins
milbemycins
Macrocyclic lactones:
phamacodynamics
MOA: ligand gated chloride channel agonists
- MLs bidn to GABA and/or glutamate-gated chloride channels with high affinity
- Very selective for the glutamate-gated channels in nematodes and arthropods, but which are lacking in mammals
Macrocyclic lactones:
usage
cattle: pour-on, injection
lice, mites, hypoderma, horn flies
Sythetic pyrethroids
Permethrin, deltamethrin, flumethrin, fenvalerate, cypermethrin, phenothrin
Drug class: pyrethroids
Synthetic Pyrethroids
Pharmacodynamics
MOA: Na+ channel agonist
- Interaction with the pyrethroid with the sodium channel causes the channel to remain open in insect nerves
- Leads to a slowing of both the activation and inactivation process → causes the now modified channel to be in a stable hyperexcitable state
- Repetivie discharges or membrane depolarization and ultimately death ofthe ectoparasite
- Extremely selective for insects over mammals
- Insect sodium channels can be as much as 100 times more sensitive than mammalian brian channels
Synthetic Pyrethroids
Pharmacokinetics
Dermal abosrption is very limited; reside in the outermost layer of the skin with littel or no penetration into the systemic circulation
More resistant to breakdown, greater residual activity
Synthetic pyrethroids
Safety / toxicitiy
Cats are more sensitive than dogs to pyrethroids - can cause neurological effects and death
Aquatic animals such as fish and invertebrates are highly susceptible to pyrethroids
Synthetic pyrethroids
Usage
Dogs and cats: shampoos, spot-on, collar
Cattle: dusts, pour-on, eartags,
Horses: sprays
Environmental control
Organophosphates
dichlorvos, coumaphos
Organophosphates
Pharmacodynamics
MOA: AchE inhibitor
- Irreversibly inhibit acetylcholinesterase by phosphorylation
- Inhibition of AChE results in accumulation of acetylcholine to cholinergic receptors
- repeated depolarization lead to paralysis and death to the parasite
Organophosphates
Products
becoming less popular for use in and around domestic animals
persistence in the environment - negatively influence the ecosystem
Old OPs approved by US EPA for use in companion or food animals species are no longer marketed or available for veterinary use
Organophosphates
Pharmacokinetics
Topical: systemic bioavailability following topical application is limited, but these are distributed across the entire coat of the animal by lateral diffusion following topical applicaiton to a localized region
Organophosphates
Safety / toxicity
Inhibition of AChE can result in muscarinic and nicotinic effects
Other drugs may potentiate the toxicity of OPs: phenothiazine tranquilizers, aminoglycodise antibiotics, and neuromuscular blocking agents such as levamisole and nicotine
Amitraz
Drug class: formamidine
Amitraz:
pharmacodynamics
MOA: octopamine receptor agonist
- Activates a- and B- adrenergic like octopamine receptors
- Inhibits neurotransmission resulting in flaccid paralysis
- Inhibits monamine oxidase that normally metabolize neurotransmitter amines present in the CNS
- No effect on cholinesterase activity
Amitraz
pharmacokinetics
Not well understood
Amitraz
Safety / toxicity
toxic to cats and horses
5-10 times label dose causes toxicity in dogs
Accidental consumption of amitraz flea collars by dogs has resulted in toxicosis
Amitraz:
Usage
Dogs: spot-on, concentrate liquid, collar
Cattle, swine: Concentrate liquid
Repellents
butoxypolypropylene glycol (stabilene), di-n-propyl isocinchomeronate (MGK 326), and diethyl-m-toluamide (DEET)
Repellents
Pharmacodynamics
MOA:
- Preventing the entry or landing of insect on hair coat, interfere with or inhibit feeding, causing disorientation
- Some repellents can be ectoparasiticidal most repellents are not ectoparasiticidal
- They prevent transmission of vector-borne diseases
Repellents:
Usage
DEET
Approved by US EPA for use in dwellings, on the human body and clothing, and pet living/sleeping quarters
Repellents
usage
MGK 326
often formulated with pyrethroids and or synergist to be used as sprays, dips, and shampoos in horses, dogs, and cats
Repellents
usage
Butoxypolypropylene glycol
formulated with a pyrethroid insecticide
