Toxicology Brief: Phenylpropanolamine toxicosis in dogs and cats

Jan 01, 2012

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Phenylpropanolamine (PPA) is a sympathomimetic drug used in dogs and cats primarily to treat urinary incontinence secondary to urethral sphincter hypotonia. It is labeled for use in dogs and is available as a solution in 25- and 50-mg/ml concentrations (Proin Drops—PRN Pharmacal); in chewable 25-, 50-, and 75-mg tablets (Proin—PRN Pharmacal, Propalin—Vétoquinol, Uricon—Neogen Corporation, Uriflex-PT—Butler Schein Animal Health); and as a 75-mg timed-release capsule (Cystolamine—Veterinary Product Laboratories).1 PPA is classified as a list 1 chemical (can be used to manufacture methamphetamine) in the United States. Restrictions regarding its sale may vary among states, and in some states it may be a controlled substance.1

Historically in people, PPA was used as a decongestant and anorectic. It was removed from both over-the-counter and prescription use in the United States in 2000 because of data that suggested PPA increases the risk of hemorrhagic stroke in people.2 It has since also been removed from the market in Canada.


PPA is readily absorbed orally, with an oral bioavailability of approximately 98% in dogs.3 In people, the onset of action is rapid, occurring within 15 to 30 minutes. It is widely distributed into multiple tissues and fluids, including the central nervous system (CNS). Approximately 80% to 90% of the drug is excreted unchanged in the urine within 24 hours of dosing.1 The serum half-life in dogs is approximately three to four hours.3 Clinical effects may persist well beyond what is expected based on the half-life.4

The recommended dosage for the immediate-release forms in dogs is 1 to 2 mg/kg given orally b.i.d.5 The dose using the time-release 75-mg capsules is one-half capsule given orally once a day for dogs weighing < 40 lb (18.2 kg), 1 capsule given orally once a day for dogs weighing 40 to 100 lb (18.2 to 45.5 kg), and 1.5 capsules given orally once a day for dogs weighing >100 lb (45.5 kg).6

The exact mechanism of PPA's action has not been determined. It is thought that it directly stimulates alpha-adrenergic receptors and indirectly stimulates both alpha-adrenergic and beta-adrenergic receptors by causing the release of norepinephrine.1 It acts primarily on peripheral alpha receptors, with a weak effect on beta receptors.7 Other pharmacologic effects of PPA include vasoconstriction, mild CNS stimulation, decreased nasal congestion, and decreased appetite. It also increases urethral sphincter tone.1