Felipedia

Pyrethrin toxicity in cats

Pyrethrins are naturally occurring compounds derived from a combination of insecticidal esters (pyrethrins, cinerins, and jasmolins) that are isolated from the flowers of Chrysanthemum cinerariaefolium and related species. Initially used on production animals from the early 1970s, their use has since gained acceptance in small animal products, and spot-on insecticides containing pyrethrins are a common method of flea control in domestic pets as a result of their efficacy, ease of administration, and overall safety. A wide range of products is available, many of which can be purchased without veterinary advice.

Permethrin contains various cis-trans ratios ranging from 40:60 to 25:75. The insecticidal effect and mammalian toxicity are related to the cis isomer content. Permethrin is a very effective insecticide with low toxicity to most mammals, and has a wide safety margin when used appropriately. It is a fat-soluble compound that is subject to rapid metabolism and excretion after absorption (oral, dermal or via the lungs). Permethrin is metabolised by ester hydrolysis in the plasma and liver, followed by hydroxylation, and glucuronide and sulfate conjugation. These products are then almost completely eliminated from the body in urine within 12 days. Enterohepatic circulation does not readily occur. Synergists (e.g. piperonyl butoxide) are often combined with pyrethrin and pyrethroid insecticides to delay their metabolism, increasing their toxicity to insects and, potentially, to mammals.

Permethrin acts as a neuro-intoxicant by interfering with the axonal sodium gate. It decreases sodium movement through cell membranes, thus suppressing potassium conduction, which inactivates the action potential, resulting in repetitive nerve firing because depolarisation does not occur. These actions on the presynaptic nerve endings lead to adverse clinical signs seen in permethrin toxicosis. The development and severity of clinical signs is proportional to the concentration of the chemical in nervous tissue. Onset of clinical signs can be within hours of exposure, but may be delayed up to 24 hrs or longer.

Cats are noted for their inability to metabolise and biotransform certain compounds and as a species are very sensitive to adverse drug reactions. The specific reason for increased sensitivity of cats to permethrin is probably complex, but thought to be associated with a deficiency in glucuronidase, which is necessary for permethrin metabolism via glucuronidation. Further, the hydrolytic enzymes that degrade pyrethroid esters have a slow rate of hydrolysis in cats, compared with other species, thus increasing their susceptibility.

Products containing permethrins, such as spot-ons, flea sprays, collars and flea shampoos, are generally intended for exclusive use in either dogs or cats and toxicity or adverse reactions can occur when label instructions are not followed. A number of preparations contain 45-65% permethrin and are intended for use in dogs only, and cats may be adversely affected after oral ingestion, topical application of concentrated products, off-label usage, or by grooming dogs that have been treated.

Diagnosis

Diagnosis of pyrethrin toxicosis can generally be made from a history of exposure and typical clinical signs, which commonly include hyperexcitability, tremors and seizures. Other signs include mydriasis, hyperaesthesia, ataxia, shaking, shivering and hyperthermia.

Treatment

Treatment of cats affected by permethrin toxicity involves stabilisation, dermal decontamination, tremor and seizure control and supportive care. Although tremors and seizures can be treated using similar methods (diazepam and propofol), seizures related to permethrin toxicity are generally refractory to diazepam in the long term. Diazepam is generally a good initial choice (given as a constant rate infusion IV), and may be beneficial when used as a part of a combination, especially with low-dose propofol administration.

Intravenous crystalloids are indicated for maintenance of intravascular fluid volume and hydration, and although permethrin appears to have no direct effect on the liver or kidneys, crystalloid therapy protects the kidneys from myoglobulin breakdown products that may be produced during tremors. Bladder care is important, given that cats affected by permethrin toxins generally have a lower-motor-neuron bladder because of the anticholinesterase activity of the permethrin toxin

Atropine is not an antidote for permethrin toxicity. A test dose of atropine (0.01-0.02 mg/kg IV) can help to distinguish organophosphate and carbamate toxicity from pyrethrin toxicosis, with a low-dose of atropine reducing/reversing the cholinergic signs (hypersalivation, bradycardia, miosis) induced by organophosphate or carbamate overdose. Low doses of atropine administered eith IM or SQ, however, can be used to control hypersalivation associated with pyrethrin exposure, but will not control nicotinic signs, tremors, seizures and ataxia. Atropine also causes tachycardia, which can be detrimental.

Gastric decontamination using emetics and activated charcoal has not been shown to decrease treatment time and is probably not indicated.

There have been no reports of long-term effects after recovery, including trauma, hypoxia or prolonged hyperthermia during seizure activity. Certain situations lead to a worse prognosis despite aggresive therapy; for example, prolonged uncontrolled seizures can cause cerebral oedema, irreversible brain damage, and traumatic damage and breakdown of muscle tissue can lead to myoglobinuria-induced nephropathy.

Misuse of permethrin spot-on products on cats can lead to severe morbidity and mortality; however, with prompt, effective treatment the prognosis is generally good.