Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

MISCELLANEOUS EXTERNAL PARASITICIDES
● Signs of poisoning include salivation, twitching of
treated areas, generalized tremors, convulsions,
respiratory failure and death.
● Treatment is symptomatic and supportive.
D-limonene
1-methyl-4-(1-methylethenyl)cyclohexene.
Clinical applications
d-limonene is a citrus fruit extract, available as an insecticidal
dip for flea control. It has been shown to be
neurotoxic to adult fleas, resulting in rapid immobilization.
Vapors as well as direct exposure result in toxicity
to fleas and toxicity is synergized by piperonyl
butoxide.
Adverse effects
● d-limonene has been considered to be of little toxic
concern, as the acute oral LD 50 in rats is more than
5000 mg/kg.
● However, errors in dilution have led to exposure of
cats to elevated dose rates 5–15 times the recommended
use rate, inducing a toxic syndrome of salivation,
muscle tremors, ataxia and hyperthermia.
● Treatment is supportive and symptomatic, with particular
attention to both decontamination and body
temperature control.
● A similar toxic syndrome has been reported in a dog,
who developed erythema multiforme major and disseminated
intravascular coagulation.
Lime sulfur
Solution of calcium polysulfides and thiosulfate.
Clinical applications
Lime sulfur is a traditional pesticide that has been
popular in cats for control of Notoedres, Sarcoptes,
Demodex, Cheyletiella, Lynxacarus, chiggers and lice
infections. Lime sulfur is fungicidal, bactericidal, keratolytic
and antipruritic. Concentrated suspensions are
diluted to 2% prior to use.
Adverse effects
● If inadequately diluted, skin irritation and scalding
may be observed.
● Lime sulfur preparations have an unpleasant
odor.
● Lime sulfur can stain light-colored coats and
tarnish silver jewelry.
● To prevent possible oral ingestion and toxicity, cats
should not be allowed to groom until the coat has
dried after treatment.
Linalool oil
3,7-dimethyl-1,6-octadien-3-ol.
Linalool oil occurs naturally in a large variety of
plants and is a constituent of citrus peel and has found
applications in perfumes and flavors.
Clinical applications
Linalool oil has been shown to kill the eggs, larvae and
pupae of the cat flea (Ctenocephalides felis) and to
eliminate adult fleas rapidly from cats immersed in a dip
charged with 10,000 mg/L linalool or 5000 mg/L linalool
plus MGK 264. Apart from the disagreeable odor
and temporary oiliness of the coat, the low vertebrate
toxicity and broad-spectrum flea activity make linalool
a possible candidate for use.
Rotenone
(2R,6as,12aS)-1,2,6,6a,12,12a-hexahydro-2-isopropenyl-8,9-dimethoxychromeno[3,4-b]furol-[2,3-h]
chromen-6-one.
Clinical applications
Rotenoid-containing plants have been used as fish
poisons for many centuries, if not millennia, but it was
not until 1892 that the active moiety was isolated, being
named rotenone in 1902. Rotenone is most widely
sourced from Derris elliptica and D. malaccensis in Asia
and from Lonchocarpus utilis and L. urucu in South
America. Plant extracts contain six rotenoids, of which
rotenone is the most active and abundant. Rotenone
solutions decompose on exposure to light or air.
Principal applications are in combination with synergists
and pyrethrins for flea and ear mite control.
Mechanism of action
Rotenone toxicity to insects results in inactivity, locomotor
instability and refusal to eat, followed by knockdown,
paralysis and slow death by respiratory failure.
Biochemically, rotenone is one of the most potent inhibitors
of the NADH dehydrogenase system, acting on
Fe-S proteins to inhibit electron transport between
NADH and ubiquinone (coenzyme Q) in both insects
and vertebrates.
Pharmacokinetics
Rotenone is sparingly soluble in water but readily
soluble in many organic solvents and oils. Around 20–
30% of an oral dose is absorbed, but this amount is
increased if administered in oil. Rotenone is rapidly
metabolized in the liver and excreted in both feces and
urine.
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