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Pseudoephedrine and phenylephrine are sympathomimetic drugs that are widely available in nonprescription nasal decongestants and cold preparations. These remedies usually also contain antihistamines and cough suppressants. Nonprescription ephedrine-containing cough and cold preparations as well as ephedrine-containing dietary supplements were widely consumed until 2004, when their use was banned by the FDA because of the unacceptable risk for toxicity. Ephedrine and ephedra-containing herbal preparations (eg, ma huang and "herbal ecstasy"), often in combination with caffeine, were also used as alternatives to the amphetamine derivative "ecstasy" or as adjuncts to body-building or weight loss programs. Phenylpropanolamine (PPA) had been marketed as a nonprescription decongestant and appetite suppressant for many years but was removed from the US market in 2000 because of an association with hemorrhagic stroke in women. The availability of nonprescription pseudoephedrine is limited in many states because it can be used to manufacture illicit methamphetamine. The FDA issued an advisory in 2008 recommending against the use of cough and cold medicines (which contain decongestants as well as antihistamines and/or dextromethorphan) to children younger than 2 years of age because of reports of serious and life-threatening side effects.


All these agents stimulate the adrenergic system, with variable effects on alpha- and beta-adrenergic receptors, depending on the compound. Generally, these agents stimulate the CNS much less than do other phenylethylamines (see "Amphetamines").

  1. PPA and phenylephrine are direct alpha-adrenergic agonists. In addition, PPA produces mild beta1-adrenergic stimulation and acts in part indirectly by enhancing norepinephrine release.

  2. Ephedrine and pseudoephedrine have both direct and indirect alpha- and beta-adrenergic activity but clinically produce more beta-adrenergic stimulation than does PPA or phenylephrine.

  3. Pharmacokinetics. Peak effects occur within 1–3 hours, although absorption may be delayed with sustained-release products. These drugs have large volumes of distribution (eg, the Vd for PPA is 2.5–5 L/kg). Elimination half-lives are 3–7 hours (see also Table II–66).


Table II–53 lists the usual therapeutic doses of each agent. Patients with autonomic insufficiency and those taking monoamine oxidase (MAO) inhibitors may be extraordinarily sensitive to these and other sympathomimetic drugs, developing severe hypertension after ingestion of even subtherapeutic doses.


  1. PPA, phenylephrine, and ephedrine have low toxic-to-therapeutic ratios. Toxicity often occurs after ingestion of just 2–3 times the therapeutic dose. Strokes and cardiac toxicity have been reported after therapeutic doses of ephedra and PPA.

  2. Pseudoephedrine is less toxic, with symptoms occurring ...

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