Current issues of ACP Journal Club are published in Annals of Internal Medicine


Phenylpropanolamine combined with brompheniramine had no acute effect on blood pressure

ACP J Club. 1992 May-June;116:78. doi:10.7326/ACPJC-1992-116-3-078

Source Citation

Petrulis AS, Imperiale TF, Speroff T. The acute effect of phenylpropanolamine and brompheniramine on blood pressure in controlled hypertension. A randomized double-blind crossover trial. J Gen Intern Med. 1991 Nov/Dec;6:503-6.



To determine whether a slow-release combination of phenylpropanolamine (PPA) and brompheniramine acutely affects blood pressure (BP) in patients with controlled hypertension.


Randomized, double-blind, placebo-controlled, crossover trial.


Outpatient hospital clinic in Cleveland, Ohio.


13 full-time employees of the medical center (mean age, 48 years [range 36 to 64 years]; mean duration of hypertension, 7 years [range 0.5 to 20 years]; 11 women) with medication-controlled hypertension were included. Volunteers with poorly controlled coronary artery disease, contraindication to PPA or brompheniramine, or concomitant use of a monoamine oxidase inhibitor were excluded. All 13 participants completed the study.


After 24-hour ambulatory BP monitoring, participants were randomly allocated to receive 1 capsule of either the sustained-release formulation of PPA (75 mg) and brompheniramine (12 mg) (n = 6) or placebo (n = 7) every 12 hours for 3 doses. After a 24-hour washout period, the other treatment was given.

Main outcome measure

Ambulatory BP was measured every 30 minutes between 0800 hours and 2400 hours, and hourly from 1200 hours to 0800 hours. The study was designed to have a > 90% chance of detecting a 10-mm Hg increase in systolic or diastolic BP from baseline using a 1-sided alpha of 0.05.

Main results

No significant difference was found for mean systolic or diastolic BP among the baseline (127/75), PPA and brompheniramine (PPA/B) (127/72), and placebo (126/73) phases. The overall difference in mean systolic and diastolic BP between the PPA/B and placebo phases was 1.1 mm Hg (95% CI -2.0 to 4.2 mm Hg) and 0.5 mm Hg (CI -2.1 to 3.2 mm Hg), respectively. During the first 4 hours of treatment, the difference in the mean change from baseline between PPA/B and placebo phases was +1.7 mm Hg (CI -5.3 to 8.7 mm Hg) for systolic BP and +0.9 mm Hg (CI -1.6 to 3.5 mm Hg) for diastolic BP, excluding a first-dose pressor effect. Urinary PPA, measured to evaluate compliance, was detected only during the PPA/B phase of the study.


Phenylpropanolamine combined with brompheniramine, when used as recommended, had no acute effect on mean blood pressure in a small group of patients with medication-controlled hypertension.

Source of funding: Division of General Internal Medicine, MetroHealth Medical Center, Cleveland, Ohio.

Address for article reprint: Dr. A.S. Petrulis, MetroHealth Medical Center, 3395 Scranton Road, Cleveland, OH 44109, USA.


This well-done study found no clinically important increase in BP with acute PPA/B. Although they did not state it in their article, the authors indicate that urine tests for all persons were PPA positive when on active PPA, and that no person showed an important rise in BP.

As the authors caution, generalizability is somewhat limited. Because PPA is a sympathomimetic agent, similar to ephedrine (and epinephrine), a dose-response effect on BP may be assumed. Only 1 dose was tested; 1 study cited by the authors detected a group BP effect with twice this dose. When untoward events are rare, lack of a detectable average BP increase does not mean that all hypertensive individuals may safely take PPA, even at this dose. The introduction notes that alarming BP increases are occasionally reported; careful rechallenge would be one way to clarify whether these isolated cases are only "anecdotal."

A broader issue arises: Even if PPA does not raise BP, should hypertensive patients take this combination? Paracelsus warned that ultimately "all substances are poisons...." PPA/B use confers other risks, including rare but serious hematologic toxicity and the possibility of overdose for adults or children. Since H1 blockers are considered to be "without value" (1) for the common cold, the combination studied may not have an acceptable risk/benefit ratio because of lack of efficacy, available alternatives (including nasal α-agonists or no pharmacotherapy), and the risk associated with widespread use: Infrequent reactions with extensive exposure can result in a significant number of adverse events.

Richard A. Reeves, MD
University of TorontoToronto, Ontario, Canada

Richard A. Reeves, MD
University of Toronto
Toronto, Ontario, Canada


1. Garrison JC. Histamine, bradykinin,5-hydroxytryptamine, and their antagonists. In: Gilman AG, Rall TW, Nies AS, Taylor P: eds. The Pharmacological Basis of Therapeutics. Toronto: Pergamon Press; 1990:575-99.