Toxicology Brief: Phenylephrine ingestion in dogs: What's the harm?

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Nov 01, 2012

Phenylephrine is a sympathomimetic amine used orally in human medicine mainly as a decongestant. It is found in several over-the-counter cold remedies. Veterinary practitioners should be aware of its toxic potential in dogs since its use has likely increased as restrictions are placed on the sale of another common over-the-counter decongestant, pseudoephedrine, because of pseudoephedrine's involvement with methamphetamine production.

EXPOSURE RISKS FOR DOGS

As a decongestant, phenylephrine is available in nasal (0.25% to 1%) and oral formulations (5- to 10-mg tablets). The oral formulations are often combined with antihistamines, analgesics, expectorants, or antitussives. In an overdose, other ingredients present in the formulation such as acetaminophen or ibuprofen are often more concerning than the phenylephrine.

Parenteral formulations of phenylephrine are used to treat hypotension in animals and people. Phenylephrine is also used as an adjunct in spinal and local anesthesia.

Ocular preparations produce mydriasis and vasoconstriction. These formulations are used for intraocular examination and surgery and to differentiate conjunctival vascular injection from deep-episcleral injection. Ocular phenylephrine is also used in the diagnosis and treatment of glaucoma, treatment and prevention of synechiae, and diagnosis and classification of Horner's syndrome.1,2

Hemorrhoid creams, ointments, and suppositories also contain phenylephrine.

TOXICOKINETICS

Phenylephrine acts directly on alpha1-adrenergic receptors. The stimulation of these receptors results in peripheral vasoconstriction and increased systolic and diastolic blood pressures. At high dosages, the stimulation of cardiac beta-adrenergic receptors may occur.3 This can lead to cardiac stimulation.

After oral exposure, phenylephrine is extensively metabolized in the gastrointestinal tract and liver.1,4 This high metabolization accounts for the low oral bioavailability of phenylephrine (38% in people).1 It is primarily excreted in the kidneys in people.1 Phenylephrine reaches a peak plasma concentration in 30 minutes.5 The half-life is two to three hours. Adverse signs typically have a rapid onset and relatively short duration.3

TOXICITY

The oral LD50 of phenylephrine in rats and mice is 350 mg/kg and 120 mg/kg, respectively.6 Because of low oral bioavailability, the acute oral toxicity is lower for phenylephrine than with other sympathomimetics such as pseudoephedrine, and parenteral administration is more likely to result in marked clinical signs of toxicosis compared with oral exposure. An oral therapeutic dosage in dogs could not be located.

Clinical signs after overdose may include2,3:

  • Gastrointestinal upset
  • Hypertension
  • Reflex bradycardia
  • Central nervous system stimulation
  • Lethargy
  • Nervousness
  • Agitation
  • Tremors
  • Seizures
  • Cerebral hemorrhage
  • Ventricular arrhythmias.