Phenylephrine

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Phenylephrine or Neo-Synephrine is an α-adrenergic receptor agonist used primarily as a decongestant, as an agent to dilate the pupil and to increase blood pressure. Phenylephrine has recently been marketed as a substitute for pseudoephedrine, (e.g. Pfizer's Sudafed (Original Formulation)) but there are recent claims that oral phenylephrine may be no more effective as a decongestant than placebo.

Decongestant
Phenylephrine is used as a decongestant, available as an oral medicine or as a nasal spray. Phenylephrine is now the most common over-the-counter (OTC) decongestant; oxymetazoline is a more common nasal spray. Pseudoephedrine was historically more common, although its notoriety as a methamphetamine precursor has led some governments to restrict its sale.

Oral phenylephrine is extensively metabolised by monoamine oxidase, an enzyme which is present in the gastrointestinal tract and the liver. Therefore, compared to orally-taken pseudoephedrine, it has a reduced and variable bioavailability of only up to 38 percent, and is therefore less effective than a nasal decongestant. Because phenylephrine is a direct selective α-adrenergic receptor agonist, it does not cause the release of endogenous noradrenaline like pseudoephedrine does. Therefore, phenylephrine is less likely to cause side-effects like central nervous system stimulation, insomnia, anxiety, irritability and restlessness.

Some popular cold remedies containing phenylephrine: Canada's hot lemon Neocitran, the United Kingdom's Lemsip, and the United States' Alka-Seltzer Cold Effervescent formula, Sudafed PE Non-Drowsy Nasal Decongestant, Robitussin CF, Tylenol Sinus, and DayQuil Capsules.

As a nasal spray, phenylephrine is available in 1% and 0.5% concentrations. It suffers some rebound congestion effects, although to a lesser degree than oxymetazoline.

Mydriatic
Phenylephrine is used as an eye drop to dilate the pupil to facilitate visualization of the retina. It is often used in combination with tropicamide. Narrow angle glaucoma is a contraindication to phenylephrine use.

Vasopressor
Phenylephrine is sometimes used as a vasopressor to increase the blood pressure in unstable patients with hypotension. Such use is more common in anesthesia or critical care practices; phenylephrine is especially useful in counteracting the hypotensive effect of epidural and subarachnoid anesthetics. It also has the advantage of not being inotropic or chronotropic, and so it strictly elevates the blood pressure without increasing the heart rate or contractility (reflex bradycardia may result from the blood pressure increase, however). This is especially useful if the heart is already tachycardic and/or has a cardiomyopathy.

Side effects
The primary side effect of phenylephrine is hypertension. Patients with congestion and hypertension are typically advised to avoid products containing phenylephrine.

Patients with a history of epilepsy and on anticonvulsant medication should not take this substance. The drug interaction might produce seizures.

Legal issues
Pseudoephedrine and phenylephrine are both used as decongestants; and until recently, pseudoephedrine was much more commonly available in the United States. This has changed because provisions of the Combat Methamphetamine Epidemic Act of 2005 placed restrictions on the sale of pseudoephedrine products to prevent the clandestine manufacture of methamphetamine. Since 2004, phenylephrine has been increasingly marketed as a substitute for pseudoephedrine; some manufacturers have changed the active ingredients of products to avoid the restrictions on sales. Phenylephrine has been off patent for a long time; there are many generic brands available.

Questions about effectiveness
Pharmacists Leslie Hendeles and Randy Hatton of the University of Florida suggested in 2006 that oral phenylephrine is ineffective as a decongestant at the 10 mg dose used, arguing that the studies used for the regulatory approval of the drug in the United States in 1976 were inadequate to prove effectiveness at the 10 mg dose and safety at higher doses. Other pharmacists have expressed concerns over phenylephrine's effectiveness as a nasal decongestant and other clinicians have indicated concern for regulatory actions that reduce the availability of pseudoephedrine. A subsequent metaanalysis by the same researchers concluded that there is insufficient evidence for its effectiveness. The matter is still under debate, though the Food and Drug Administration has stood by its 1976 approval.