Phenylpropanolamine

Acutrim®, Dexatrim®, Phenoxine®, Phenyldrine®, Propagest®, Rhindecon®

[Description] [Mechanism of Action] [Pharmacokinetics] [OBRA/Patient Information]

Description: Phenylpropanolamine (PPA) is a non-prescription oral sympathomimetic agent. Phenylpropanolamine is structurally similar to pseudoephedrine; both are used for the treatment of nasal congestion. PPA is one of the few OTC products available that is also used as an appetite suppressant to promote weight loss; it has been shown to be more effective than pseudoephedrine for the short-term treatment of obesity. It is available as a chewing gum for this purpose. PPA has less CNS side effects compared to ephedrine, but has greater propensity for cardiovascular side effects compared to pseudoephedrine. PPA has been associated with significant elevations in blood pressure and associated complications, especially at higher doses or when used in high risk patients or patients with a history of substance abuse. Tachyphylaxis and rebound congestion are associated with PPA when used as a nasal decongestant. Phenylpropanolamine was approved by the FDA in 1939. In 1996, a law was passed to report sales of excessive quantities of phenylpropanolamine. This was done in an attempt to control the use of phenylpropanolamine as a substrate for the illegal synthesis of amphetamine and methamphetamine.

Mechanism of Action: Phenylpropanolamine acts directly on both alpha- and, to a lesser degree, beta-adrenergic receptors. PPA also has an indirect effect by releasing norepinephrine from its storage sites. Secondary to direct stimulation of alpha-adrenergic receptors in the mucosa of the respiratory tract, PPA produces vasoconstriction, which shrinks swollen nasal mucous membranes; reduces tissue hyperemia, edema, and nasal congestion; and increases nasal airway patency. PPA indirectly stimulates beta-receptors producing tachycardia, and a positive inotropic effect. These cardiovascular actions can result in an increase in blood pressure. PPA has not demonstrated a bronchodilating effect.

Pharmacokinetics: Phenylpropanolamine is administered orally as tablets or capsules, or chewed as pieces of gum. It is rapidly absorbed after oral administration and nasal decongestion occurs within 30 minutes and persists up to 3 hours. Detectable serum concentrations are seen within 10 minutes and the mean time to peak concentration is 1.5 hours. The time to peak concentration of the extended-release preparations is approximately 3.5 hours with a duration of activity of 12-16 hours. PPA is widely distributed into extracellular sites. PPA is approximately 20% protein bound.

Phenylpropanolamine is approximately 90% excreted unchanged in the urine; it is minimally metabolized in the liver to an active hydroxylated metabolite. PPA is a weak base and alkalinization of the urine decreases urinary excretion and increases tubular reabsorption. If the urine is acidified to a pH of 5 or less, renal excretion of PPA is increased. PPA has a half life of approximately 3.5 hours and reaches steady state concentrations in 12 hours. It is not known whether phenylpropanolamine is removed by hemodialysis.