In the mid 2000s in the US, due to issues of drug enforcement, pseudoephedrine containing medications were brought behind the pharmacy counter and in most cases require ID, and phenylephrine was substituted in most over-the-counter products.

Pseudoephedrine increases the amount of endogenous norepinephrine, whereas phenylephrine works on α1-adrenergic receptors directly.

There are numerous cases where experts have spoken out about the effectiveness of phenylephrine, so it likely is a less effective substitute for pseudoephedrine in its main role as a decongestant.

What I'm curious about is whether there are clinical indications for which the phenylephrine is actually preferred (so situations where the α1-agonist nature without the increase of endogenous NE is sought after)?

  • $\begingroup$ I suppose phenylephrine might be indicated in cases where there is an interest in maintaining levels of neurepinephrine, such as when antidepressants or other medications are being administered. $\endgroup$
    – MattDMo
    Commented Dec 1, 2012 at 13:39

1 Answer 1


Yes, in all clinical situations where you need pure vasoconstriction without heart rate acceleration (mostly valid for iv administration route).

The classical example would be in the operative setting. If the patient is in a hypotensive state due to hypnotic drugs, opiates, etc. and has atherosclerosis, you will prefer a drug that will reverse the hypotension without an increase in heart rate, i.e phenylephrine. The reason is that an increase in heart rate will shorten the duration of diastole, which will therefore shorten the time interval where the coronary arteries are perfused. Moreover, an increase in heart rate also means an increase in heart oxygen consumption. The end result will be an imbalance between oxygen input and requirement, i.e ischemia and potential heart infarction.

Conversely, if you have a patient with aortic valve insufficiency (regurgitation), you will prefer ephedrine (or any drug with beta 1 activity), because you will be aiming at shortening the available time for regurgitation to occur.

  • 1
    $\begingroup$ Would phenylephrine be called "non-inotropic" or something of that nature, or is that an abuse of terminology? $\endgroup$
    – jonsca
    Commented Sep 4, 2014 at 17:45
  • 1
    $\begingroup$ @jonsca it is true that (to my knownledge) phenylephrine has no inotropic effect, and can be called as such. But since it is the only pure alpha agonist commonly used for blood pressure control, it isn't really defined as part of a "non-inotropic" class in usual medical jargon. $\endgroup$
    – Raoul
    Commented Sep 4, 2014 at 17:48

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