Phenylephrine is a

medication A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy ( pharmacotherapy) is an important part of the medical field and ...

primarily used as a

decongestant A decongestant, or nasal decongestant, is a type of pharmaceutical drug that is used to relieve nasal congestion in the upper respiratory tract. The active ingredient in most decongestants is either pseudoephedrine or phenylephrine (the latter ...

, to dilate the pupil, to increase

blood pressure Blood pressure (BP) is the pressure of circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term "blood pressure ...

, and to relieve

hemorrhoids Hemorrhoids (or haemorrhoids), also known as piles, are vascular structures in the anal canal. In their normal state, they are cushions that help with stool control. They become a disease when swollen or inflamed; the unqualified term ''h ...

. In the

United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country Continental United States, primarily located in North America. It consists of 50 U.S. state, states, a Washington, D.C., ...

, it was previously used orally as an

over-the-counter Over-the-counter (OTC) drugs are medicines sold directly to a consumer without a requirement for a prescription from a healthcare professional, as opposed to prescription drugs, which may be supplied only to consumers possessing a valid prescr ...

decongestant to relieve nasal congestion due to

sinusitis Sinusitis, also known as rhinosinusitis, is inflammation of the mucous membranes that line the sinuses resulting in symptoms that may include thick nasal mucus, a plugged nose, and facial pain. Other signs and symptoms may include fever, head ...

, but this use was discontinued in 2007. As of 2022, its use as a nasal decongestant in other applications still persists. Phenylephrine can be taken by mouth, as a nasal spray, given by injection into a vein or muscle, or applied to the skin. Common side effects when taken by mouth or injected include nausea, vomiting, headache, and anxiety. Use on hemorrhoids is generally well tolerated. Severe side effects may include a slow heart rate, intestinal ischemia,

chest pain Chest pain is pain or discomfort in the chest, typically the front of the chest. It may be described as sharp, dull, pressure, heaviness or squeezing. Associated symptoms may include pain in the shoulder, arm, upper abdomen, or jaw, along with ...

kidney failure Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...

, and

tissue death Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated diges ...

at the site of injection. It is unclear if use during

pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ...

breastfeeding Breastfeeding, or nursing, is the process by which human breast milk is fed to a child. Breast milk may be from the breast, or may be expressed by hand or pumped and fed to the infant. The World Health Organization (WHO) recommends that bre ...

is safe. Phenylephrine is a selective α₁-adrenergic receptor

agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ag ...

which results in the

constriction Constriction is a method used by various snake species to kill or subdue their prey. Although some species of venomous and mildly venomous snakes do use constriction to subdue their prey, most snakes which use constriction lack venom. The snake i ...

of both

arteries An artery (plural arteries) () is a blood vessel in humans and most animals that takes blood away from the heart to one or more parts of the body (tissues, lungs, brain etc.). Most arteries carry oxygenated blood; the two exceptions are the pu ...

and

veins Veins are blood vessels in humans and most other animals that carry blood towards the heart. Most veins carry deoxygenated blood from the tissues back to the heart; exceptions are the pulmonary and umbilical veins, both of which carry oxygenated ...

. Phenylephrine was patented in 1927 and came into medical use in 1938. It is available as a

generic medication A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ...

. Unlike

pseudoephedrine Pseudoephedrine (PSE) is a sympathomimetic drug of the phenethylamine and amphetamine chemical classes. It may be used as a nasal/sinus decongestant, as a stimulant, or as a wakefulness-promoting agent in higher doses. It was first charact ...

, abuse of phenylephrine is very uncommon. As of 2022, there is push back on the effectiveness of phenylephrine as a decongestant, often fused with the supposition that phenylephrine is coasting on its historical status within the United States

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

as a substitute for

as a decongestant, whose availability has been restricted due to a potential for use in the illicit synthesis of

methamphetamine Methamphetamine (contracted from ) is a potent central nervous system (CNS) stimulant that is mainly used as a recreational drug and less commonly as a second-line treatment for attention deficit hyperactivity disorder and obesity. Methamp ...

Medical uses

Decongestant

Phenylephrine is used as a

sold as an oral medicine or as a

nasal spray Nasal sprays are used to deliver medications locally in the nasal cavities or systemically. They are used locally for conditions such as nasal congestion and allergic rhinitis. In some situations, the nasal delivery route is preferred for syst ...

. It is a common ingredient in

decongestants in the United States. Phenylephrine is used as an alternative for pseudoephedrine in decongestant medicines due to pseudoephedrine's use in the illicit manufacture of methamphetamine. Its efficacy as an oral decongestant has been questioned, with several independent studies finding that it provided no more relief to sinus congestion than a placebo. A 2007 meta-analysis concluded that the evidence for its effectiveness is insufficient,(published online Jan 2007) though another meta-analysis published shortly thereafter by researchers from

GlaxoSmithKline GSK plc, formerly GlaxoSmithKline plc, is a British multinational pharmaceutical and biotechnology company with global headquarters in London, England. Established in 2000 by a merger of Glaxo Wellcome and SmithKline Beecham. GSK is the tent ...

found the standard 10-mg dose to be more effective than a placebo; however, the fact that GSK markets many products containing phenylephrine has raised some speculation regarding selective publishing and other controversial techniques. A 2007 study by

Wyeth Consumer Healthcare Wyeth, LLC was an American pharmaceutical company. The company was founded in Philadelphia, Pennsylvania, in 1860 as ''John Wyeth and Brother''. It was later known, in the early 1930s, as American Home Products, before being renamed to Wyeth i ...

notes that 7 studies available in 1976 support the efficacy of phenylephrine at a 10 mg dosage. Two studies published in 2009, examined the effects of phenylephrine on symptoms of

allergic rhinitis Allergic rhinitis, of which the seasonal type is called hay fever, is a type of inflammation in the nose that occurs when the immune system overreacts to allergens in the air. Signs and symptoms include a runny or stuffy nose, sneezing, red, ...

by exposing people to pollen in a controlled, indoor environment. Neither study was able to distinguish between the effects of phenylephrine or a placebo. Pseudoephedrine and loratadine– montelukast therapy were found to be significantly more effective than both phenylephrine and placebo. The

withdrew the indication "for the temporary relief of nasal congestion associated with sinusitis" in 2007. Pseudoephedrine was previously much more commonly available in the United States, however, provisions of the Combat Methamphetamine Epidemic Act of 2005 placed restrictions on the sale of pseudoephedrine products to prevent the clandestine manufacture of

. 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 A patent is a type of intellectual property that gives its owner the legal right to exclude others from making, using, or selling an invention for a limited period of time in exchange for publishing an enabling disclosure of the invention."A ...

for some time, and many generic brands are available.

Hemorrhoids

Hemorrhoids Hemorrhoids (or haemorrhoids), also known as piles, are vascular structures in the anal canal. In their normal state, they are cushions that help with stool control. They become a disease when swollen or inflamed; the unqualified term ''h ...

are caused by swollen

in the

rectal The rectum is the final straight portion of the large intestine in humans and some other mammals, and the gut in others. The adult human rectum is about long, and begins at the rectosigmoid junction (the end of the sigmoid colon) at the le ...

area. Phenylephrine can be used topically to prevent symptoms of hemorrhoids. Phenylephrine causes the constriction of vascular smooth muscle and is often used in the treatment of hemorrhoids presumably to narrow the swollen veins and relieve the attendant pain. However, veins—unlike arteries—contain less vascular smooth muscle in their walls so the mechanism by which pain relief is achieved is likely related to something other than vascular change alone. Products for treatment may also include substances that will form a protective barrier over the inflamed area, resulting in less pain when

feces Feces ( or faeces), known colloquially and in slang as poo and poop, are the solid or semi-solid remains of food that was not digested in the small intestine, and has been broken down by bacteria in the large intestine. Feces contain a rela ...

are passed.

Pupil dilation

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 Tropicamide, sold under the brand name Mydriacyl among others, is a medication used to dilate the pupil and help with examination of the eye. Specifically it is used to help examine the back of the eye. It is applied as eye drops. Effects occ ...

as a synergist when tropicamide alone is not sufficient. Narrow-angle

glaucoma Glaucoma is a group of eye diseases that result in damage to the optic nerve (or retina) and cause vision loss. The most common type is open-angle (wide angle, chronic simple) glaucoma, in which the drainage angle for aqueous humor, fluid withi ...

is a

contraindication In medicine, a contraindication is a condition that serves as a reason not to take a certain medical treatment due to the harm that it would cause the patient. Contraindication is the opposite of indication, which is a reason to use a certain tre ...

to phenylephrine use. As a mydriatic, it is available in 2.5% and 10% minims. Phenylephrine eye drops are applied to the eye after a topical anesthetic is applied.

Intraocular bleeding

Phenylephrine has been used as an intracameral injection into the anterior chamber of the eye to arrest intraocular bleeding occurring during cataract and glaucoma surgery.

Vasopressor

Phenylephrine is commonly used as a

vasopressor An antihypotensive agent, also known as a vasopressor agent or simply vasopressor, or pressor, is any substance, whether endogenous or a medication, that tends to raise low blood pressure. Some antihypotensive drugs act as vasoconstrictors to i ...

to increase the blood pressure in unstable patients with

hypotension Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the di ...

, especially resulting from septic shock. Such use is common in anesthesia or critical-care practices; it is especially useful in counteracting the hypotensive effect of

epidural Epidural administration (from Ancient Greek ἐπί, , upon" + ''dura mater'') is a method of medication administration in which a medicine is injected into the epidural space around the spinal cord. The epidural route is used by physicians an ...

and

subarachnoid In anatomy, the meninges (, ''singular:'' meninx ( or ), ) are the three membranes that envelop the brain and spinal cord. In mammals, the meninges are the dura mater, the arachnoid mater, and the pia mater. Cerebrospinal fluid is located in t ...

anesthetics An anesthetic (American English) or anaesthetic (British English; see spelling differences) is a drug used to induce anesthesia ⁠— ⁠in other words, to result in a temporary loss of sensation or awareness. They may be divided into two ...

, as well as the vasodilating effect of bacterial toxins and the inflammatory response in

sepsis Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...

and systemic inflammatory response syndrome. The elimination half life of phenylephrine is about 2.5 to 3.0 hours. The clinical effects of a single intravenous bolus dose of phenylephrine are short lived and needs to be repeated every 10–15 minutes. Commonly the drug is given as a carefully titrated intravenous infusion with a syringe pump or volumetric pump. Because of its vasoconstrictive effect, phenylephrine can cause severe

necrosis Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated diges ...

if it infiltrates the surrounding tissues. Because of this, it should be given through a central line if at all possible. Damage may be prevented or mitigated by infiltrating the tissue with the alpha blocker phentolamine by subcutaneous injection. Phenylephrine hydrochloride at 0.25% is used as a vasoconstrictor in some

suppository A suppository is a dosage form used to deliver medications by insertion into a body orifice where it dissolves or melts to exert local or systemic effects. There are three types of suppositories, each to insert into a different sections: rectal ...

formulations. Recently, Phenylephrine has been used to treat conditions of orthostatic intolerance such as

postural orthostatic tachycardia syndrome Postural orthostatic tachycardia syndrome (POTS) is a condition characterized by an abnormally large increase in heart rate upon standing. Symptoms may include lightheadedness, brain fog, blurred vision, weakness, fatigue, headaches, heart p ...

- where by activation of venous alpha 1 adrenoreceptors increases venous return and stroke volume which improves symptoms.

Priapism

Phenylephrine is used to treat priapism. It is diluted with normal saline and injected directly into the corpora cavernosa. The mechanism of action is to cause constriction of the blood vessels entering into the penis, thus causing decreased blood flow and relieving the priapism. An injection is given every 3–5 minutes. If priapism is not resolved in one hour, another form of therapy is considered.

Side effects

Phenylephrine may cause side effects such as headache,

reflex bradycardia Reflex bradycardia is a bradycardia (decrease in heart rate) in response to the baroreceptor reflex, one of the body's homeostatic mechanisms for preventing abnormal increases in blood pressure. In the presence of high mean arterial pressure, the ...

, excitability, restlessness and cardiac arrhythmias. Phenylephrine is not suggested for use in people with hypertension.

Heart

The primary side effect of phenylephrine is

high blood pressure Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...

. People with high blood pressure are typically advised to avoid products containing it. Because this medication is a

sympathomimetic Sympathomimetic drugs (also known as adrenergic drugs and adrenergic amines) are stimulant compounds which mimic the effects of endogenous agonists of the sympathetic nervous system. Examples of sympathomimetic effects include increases in hea ...

amine without beta-adrenergic activity, it does not increase contractility force and output of the cardiac muscle. It may increase blood pressure resulting in a slow heart rate through stimulation of vascular (likely carotid) baroreceptors. A common side effect during IV administration is reflex bradycardia. The low concentration eye drops do not cause blood pressure changes and the changes with the higher dose drops do not last long.

Other

Prostatic hyperplasia Benign prostatic hyperplasia (BPH), also called prostate enlargement, is a noncancerous increase in size of the prostate gland. Symptoms may include frequent urination, trouble starting to urinate, weak stream, urinary retention, inability to u ...

can also be worsened by use, and chronic use can lead to rebound hyperemia. People with a history of anxiety or panic disorders, or on anticonvulsant medication for epilepsy should not take this substance. The drug interaction might produce seizures. Some patients have been shown to have an upset stomach, severe abdominal cramping, and vomiting issues connected to taking this drug. Phenylephrine is pregnancy category C. Due to the lack of studies done in animals and in humans, it is not known whether there is harm to the fetus. Phenylephrine should only be given to pregnant women who have a clear need. Extended use may cause

rhinitis medicamentosa Rhinitis medicamentosa (or RM) is a condition of rebound nasal congestion suspected to be brought on by extended use of topical decongestants (e.g., oxymetazoline, phenylephrine, xylometazoline, and naphazoline nasal sprays) and certain oral medic ...

, a condition of rebound

nasal congestion Nasal congestion is the blockage of nasal breathing usually due to membranes lining the nose becoming swollen from inflamed blood vessels. Background In about 85% of cases, nasal congestion leads to mouth breathing rather than nasal breathin ...

Interactions

The increase in

effect of phenylephrine may be increased by drugs such as

monoamine oxidase inhibitor Monoamine oxidase inhibitors (MAOIs) are a class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as effective antidepressants, esp ...

tricyclic antidepressant Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants, which is important for the management of depression. They are second-line drugs next to SSRIs. TCAs were discovered in the early 1950s and wer ...

s, and

hydrocortisone Hydrocortisone is the name for the hormone cortisol when supplied as a medication. Uses include conditions such as adrenocortical insufficiency, adrenogenital syndrome, high blood calcium, thyroiditis, rheumatoid arthritis, dermatitis, asthm ...

. Patients taking these medications may need a lower dose of phenylephrine to achieve a similar increase in blood pressure. Drugs that may decrease the effects of phenylephrine may include

calcium channel blockers Calcium channel blockers (CCB), calcium channel antagonists or calcium antagonists are a group of medications that disrupt the movement of calcium () through calcium channels. Calcium channel blockers are used as antihypertensive drugs, i.e., as ...

, ACE inhibitors and

benzodiazepine Benzodiazepines (BZD, BDZ, BZs), sometimes called "benzos", are a class of depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat conditions such as anxiety disorders, ...

s. Patients taking these medications may need a higher dose of phenylephrine to achieve a comparable increase in blood pressure.

Pharmacology

Pharmacodynamics

Phenylephrine is a sympathomimetic drug, which means that it mimics the actions of epinephrine (commonly known as adrenaline) or norepinephrine. Phenylephrine selectively binds to alpha-1 receptors which causes venous and arterial vasoconstriction. Whereas pseudoephedrine causes both vasoconstriction and increase of mucociliary clearance through its nonspecific adrenergic activity, phenylephrine's selective α-adrenergic agonism causes vasoconstriction alone, creating a difference in their methods of action.

Pharmacokinetics

Oral phenylephrine is extensively

metabolized Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...

monoamine oxidase Monoamine oxidases (MAO) () are a family of enzymes that catalyze the oxidation of monoamines, employing oxygen to clip off their amine group. They are found bound to the outer membrane of mitochondria in most cell types of the body. The firs ...

, an

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...

that is present on the mitochondrial membrane of cells throughout the body. Compared to intravenous pseudoephedrine, phenylephrine has a reduced and variable

bioavailability In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation. By definition, when a medication is administered intravenously, its bioavailability is 100%. Ho ...

; only up to 38%.

References

External links

* {{Portal bar , Medicine Alpha-1 adrenergic receptor agonists Amines Cardiac stimulants Phenylethanolamines Phenols Rhinology Topical decongestants Vasoconstrictors Wikipedia medicine articles ready to translate