Phenylephrine

{{Short description|Decongestant medication}} {{Use dmy dates|date=May 2022}} {{cs1 config |name-list-style=vanc |display-authors=6}} {{Infobox drug | Watchedfields = changed | verifiedrevid = 464201108 | image = Phenylephrine v2.svg | image_class = skin-invert-image | alt = Skeletal formula of phenylephrine | image2 = (R)-Phenylephrine molecule ball.png | image_class2 = bg-transparent | alt2 = Ball-and-stick model of the phenylephrine molecule

| pronounce = {{IPAc-en|ˌ|f|ɛ|n|əl|ˈ|ɛ|f|r|iː|n|,_|f|iː|-|,_|-|ɪ|n|audio=LL-Q1860 (eng)-Naomi Persephone Amethyst (NaomiAmethyst)-phenylephrine.wav}} | tradename = Neosynephrine, Sudafed PE, others<ref name="Elks2014" /><ref name="IndexNominum2000" /><ref name="DrugBank" /><ref name="Drugs.com-International" /> | Drugs.com = {{drugs.com|monograph|phenylephrine}} | MedlinePlus = | licence_EU = yes | DailyMedID = Phenylephrine | licence_US = | pregnancy_AU =  | pregnancy_AU_comment = | pregnancy_category = | routes_of_administration = By mouth, intranasal, ophthalmic, intravenous, intramuscular, rectal<ref name="RichardsLopezMaani2023" /><ref name="Drugs@FDA" /><ref name="DailyMed" /> | class = α1-adrenergic receptor agonist; vasopressor | ATCvet = | ATC_prefix = C01  | ATC_suffix = CA06 | ATC_supplemental = {{ATC|R01|AA04}}, {{ATC|R01|AB01}} (combinations), {{ATC|R01|BA03}}, {{ATC|S01|FB01}}, {{ATC|S01|GA05}}, {{ATC|C05|AX06}}

| legal_AU = S2 | legal_AU_comment = | legal_BR =  | legal_BR_comment = | legal_CA =  | legal_CA_comment = | legal_DE =  | legal_DE_comment = | legal_NZ = OTC | legal_UK = GSL | legal_UK_comment = | legal_US = OTC | legal_US_comment = /{{nbsp}}Rx-only | legal_EU = | legal_EU_comment = | legal_UN =  | legal_UN_comment = | legal_status =

| bioavailability = Oral: conflicting—38%<ref name="Eccles2007" /><ref name="DrugBank" /><ref name="ChuaBenrimojTriggs1989" /><ref name="Medsafe2004" /> or 0.003%<ref name="AtkinsonPottsAnderson2015" /> | protein_bound = 95%{{Citation needed|date=August 2024}} | metabolism = Liver and intestines (via oxidative deamination by MAO-A and MAO-B; sulfation; glucuronidation)<ref name="RichardsLopezMaani2023" /><ref name="Eccles2007" /><ref name="DrugBank" /><ref name="AtkinsonPottsAnderson2015" /><ref name="ChuaBenrimojTriggs1989" /> | metabolites = • [https://pubchem.ncbi.nlm.nih.gov/compound/3-Hydroxymandelic-acid ''meta''-Hydroxymandelic acid]<ref name="ChuaBenrimojTriggs1989" /><ref name="DrugBank" /> • Sulfate conjugates<ref name="ChuaBenrimojTriggs1989" /><ref name="DrugBank" /> • Glucuronide conjugates<ref name="ChuaBenrimojTriggs1989" /> | onset = IV: Very rapid<ref name=AHFS2022/> Oral: 15–20{{nbsp}}min<ref name=AHFS2022/><ref name="ChuaBenrimojTriggs1989" /> Intranasal: <2{{nbsp}}min<ref name="ChuaBenrimojTriggs1989" /> Eye drop: <30{{nbsp}}min<ref name="ChuaBenrimojTriggs1989" /> | elimination_half-life = 2–3{{nbsp}}hours<ref name="Eccles2007" /><ref name="RichardsLopezMaani2023" /><ref name="DrugBank" /><ref name="KanferDowseVuma1993" /> | duration_of_action = IV: 20 min–5 h<ref name=AHFS2022/><ref name="ChuaBenrimojTriggs1989" /> Oral: 2–4{{nbsp}}h<ref name=AHFS2022/><ref name="ChuaBenrimojTriggs1989" /> Intranasal: 0.5–4{{nbsp}}h<ref name="ChuaBenrimojTriggs1989" /> Eye drop: 3–7{{nbsp}}h<ref name="ChuaBenrimojTriggs1989" /> | excretion = Urine: 86% (3–16% unchanged)<ref name="RichardsLopezMaani2023" /><ref name="Eccles2007" /><ref name="DrugBank" />

| CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 59-42-7 | CAS_number2 = 61-76-7 | CAS_supplemental = | PubChem = 6041 | IUPHAR_ligand = 485 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB00388 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 5818 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 1WS297W6MV | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D08365 | KEGG2 = D00511 | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 8093 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 1215 | NIAID_ChemDB = | PDB_ligand = | synonyms = Phenephrine; Fenefrine; L-''m''-Synephrine; Metaoxedrine; Neo-Oxedrine; Mesatonum; Neosynephrine; Adrianol; (''R'')-β,3-Dihydroxy-''N''-methylphenethylamine<ref name="Elks2014" /><ref name="IndexNominum2000" /><ref name="Drugs.com-International" />

| IUPAC_name = 3-[(1''R'')-1-Hydroxy-2-(methylamino)ethyl]phenol | C = 9 | H = 13 | N = 1 | O = 2 | SMILES = O[C@H](c1cc(O)ccc1)CNC | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C9H13NO2/c1-10-6-9(12)7-3-2-4-8(11)5-7/h2-5,9-12H,6H2,1H3/t9-/m0/s1 | StdInChI_comment = | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = SONNWYBIRXJNDC-VIFPVBQESA-N }}

'''Phenylephrine''', sold under the brand names '''Neosynephrine''' and '''Sudafed PE''' among others, is a medication used as a decongestant for uncomplicated nasal congestion in the form of a nasal spray or oral tablet,<ref name="RichardsLopezMaani2023">{{cite book | vauthors = Richards E, Lopez MJ, Maani CV |chapter = Phenylephrine |date=2023 | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK534801/ | title = StatPearls |access-date=2023-04-27 |place=Treasure Island, Florida |publisher=StatPearls Publishing |pmid=30521222 }}</ref> intravenously in cases of low blood pressure, or as a suppository to relieve hemorrhoids.<ref name="AHFS2022">{{cite web |date=2 March 2022 |title=Phenylephrine Monograph for Professionals |url=https://www.drugs.com/monograph/phenylephrine.html |access-date=9 May 2022 |website=Drugs.com |publisher=AHFS |quote=However, efficacy of oral phenylephrine for this use [as a decongestant] has been questioned.}}</ref><ref name="BNF76" /> It can also be applied to the skin.<ref name="AHFS2022" /><ref name="RichardsLopezMaani2023" />

Common side effects when taken by mouth or injected include nausea, vomiting, headache, and anxiety.<ref name=AHFS2022/> Use on hemorrhoids is generally well tolerated.<ref name=AHFS2022/> Severe side effects may include a slow heart rate, intestinal ischemia, chest pain, kidney failure, and tissue death at the site of injection.<ref name=AHFS2022/><ref name=BNF76/> It is unclear whether its use during pregnancy and breastfeeding is safe.<ref name=AHFS2022/> Phenylephrine is a selective α1-adrenergic receptor agonist with minimal to no β-adrenergic receptor agonist activity or induction of norepinephrine release.<ref name="RichardsLopezMaani2023" /><ref name="Eccles2007" /><ref name="ODonnell1995" /> It causes constriction of both arteries and veins.<ref name=AHFS2022/>

Phenylephrine was patented in 1933<ref name= "patent">{{US Patent|1932347}}, application 1928, expired 1950</ref> and came into medical use in 1938.<ref name=Fis2006>{{cite book| vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery|date=2006|publisher=John Wiley & Sons|isbn=9783527607495|page=541|url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA541}}</ref> It is available as a generic medication.<ref name="BNF76">{{Cite book |url=https://books.google.com/books?id=EPFomgEACAAJ |title=BNF 76 : September 2018 - March 2019 | publisher = British Medical Association, Royal Pharmaceutical Society of Great Britain | author = Joint Formulary Committee |year=2018 |isbn=9780857113382 |location=London |pages=188–189 |oclc=1021215075}}</ref><ref>{{cite web | title=Competitive Generic Therapy Approvals | website=U.S. Food and Drug Administration (FDA) | date=29 June 2023 | url=https://www.fda.gov/drugs/generic-drugs/competitive-generic-therapy-approvals | access-date=29 June 2023 | archive-date=29 June 2023 | archive-url=https://web.archive.org/web/20230629233651/https://www.fda.gov/drugs/generic-drugs/competitive-generic-therapy-approvals | url-status=dead }}</ref><ref>{{cite web | title=First Generic Drug Approvals 2023 | website=U.S. Food and Drug Administration (FDA) | date=30 May 2023 | url=https://www.fda.gov/drugs/drug-and-biologic-approval-and-ind-activity-reports/first-generic-drug-approvals | archive-url=https://web.archive.org/web/20230630003621/https://www.fda.gov/drugs/drug-and-biologic-approval-and-ind-activity-reports/first-generic-drug-approvals | archive-date=30 June 2023 | url-status=live | access-date=30 June 2023}}</ref> Unlike pseudoephedrine, abuse of phenylephrine is very uncommon.<ref>{{cite web |title=Max Strength Decongestant Tablets |url=http://www.mhra.gov.uk/home/groups/par/documents/websiteresources/con014437.pdf |url-status=dead |archive-url=https://web.archive.org/web/20190819052429/http://www.mhra.gov.uk/home/groups/par/documents/websiteresources/con014437.pdf |archive-date=19 August 2019 |access-date=10 January 2019 |website=www.mhra.gov.uk |page=10}}</ref> Its effectiveness as an oral nasal decongestant has been questioned.<ref name="AHFS2022" /><ref name="Hatton2022">{{cite journal |vauthors=Hatton RC, Hendeles L |date=March 2022 |title=Why Is Oral Phenylephrine on the Market After Compelling Evidence of Its Ineffectiveness as a Decongestant? |journal=Ann Pharmacother |volume=56 |issue=11 |pages=1275–1278 |doi=10.1177/10600280221081526 |pmid=35337187 |s2cid=247712448}}</ref><ref name="Lowe2022">{{cite journal |vauthors=Lowe D |date=March 2022 |title=The Uselessness of Phenylephrine |url=https://www.science.org/content/blog-post/uselessness-phenylephrine |journal=Science |type=blog}}</ref> In 2023, a U.S. Food and Drug Administration (FDA) panel concluded that the drug was ineffective as a nasal decongestant when taken orally, performing no better than placebo.<ref name="christensen23" /> In November 2024, the FDA proposed to remove oral phenylephrine as an active ingredient that can be used in over-the-counter (OTC) monograph drug products for the temporary relief of nasal congestion.<ref name="FDA PR 20241107">{{cite press release | title=FDA Proposes Ending Use of Oral Phenylephrine as OTC Monograph Nasal Decongestant Active Ingredient After Extensive Review | website=U.S. Food and Drug Administration (FDA) | date=7 November 2024 | url=https://www.fda.gov/news-events/press-announcements/fda-proposes-ending-use-oral-phenylephrine-otc-monograph-nasal-decongestant-active-ingredient-after | archive-url=https://web.archive.org/web/20241107144040/https://www.fda.gov/news-events/press-announcements/fda-proposes-ending-use-oral-phenylephrine-otc-monograph-nasal-decongestant-active-ingredient-after | url-status=dead | archive-date=7 November 2024 | access-date=10 November 2024}}</ref>

== Medical uses ==

=== Decongestant === {{Globalize|section|US-centric section|date=January 2024}} {{Unbalanced|section|reason=|date=July 2024}}

Phenylephrine is used as an alternative to pseudoephedrine as a decongestant, the availability of which has been restricted in some countries due to a potential for use in the illicit synthesis of methamphetamine.<ref name="Presley_2018">{{cite journal | vauthors = Presley B, Bianchi B, Coleman J, Diamond F, McNally G | title = Efficiency of extraction and conversion of pseudoephedrine to methamphetamine from tamper-resistant and non-tamper-resistant formulations | journal = Journal of Pharmaceutical and Biomedical Analysis | volume = 156 | pages = 16–22 | date = July 2018 | pmid = 29684907 | doi = 10.1016/j.jpba.2018.04.016 | s2cid = 13660478 | doi-access = free }}</ref> 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.<ref name="danzig09">{{cite journal | vauthors = Horak F, Zieglmayer P, Zieglmayer R, Lemell P, Yao R, Staudinger H, Danzig M | title = A placebo-controlled study of the nasal decongestant effect of phenylephrine and pseudoephedrine in the Vienna Challenge Chamber | journal = Annals of Allergy, Asthma & Immunology | volume = 102 | issue = 2 | pages = 116–20 | date = February 2009 | pmid = 19230461 | doi = 10.1016/S1081-1206(10)60240-2 | publication-date = February 2009 |quote = Phenylephrine was not significantly different from placebo in the primary end point.}}</ref><ref name="yao09">{{cite journal | vauthors = Day JH, Briscoe MP, Ratz JD, Danzig M, Yao R | title = Efficacy of loratadine-montelukast on nasal congestion in patients with seasonal allergic rhinitis in an environmental exposure unit | journal = Annals of Allergy, Asthma & Immunology | volume = 102 | issue = 4 | pages = 328–38 | date = April 2009 | pmid = 19441605 | doi = 10.1016/S1081-1206(10)60339-0 |quote = There were no statistically significant differences between phenylephrine and placebo for any measures.}}</ref><ref name="Hendeles2006">{{cite journal | vauthors = Hendeles L, Hatton RC | title = Oral phenylephrine: an ineffective replacement for pseudoephedrine? | journal = The Journal of Allergy and Clinical Immunology | volume = 118 | issue = 1 | pages = 279–80 | date = July 2006 | pmid = 16815167 | doi = 10.1016/j.jaci.2006.03.002 | doi-access = free }}</ref>

A 2007 meta-analysis concluded that the evidence for its effectiveness is insufficient,<ref name="Annals">{{cite journal | vauthors = Hatton RC, Winterstein AG, McKelvey RP, Shuster J, Hendeles L | title = Efficacy and safety of oral phenylephrine: systematic review and meta-analysis | journal = The Annals of Pharmacotherapy | volume = 41 | issue = 3 | pages = 381–90 | date = March 2007 | pmid = 17264159 | doi = 10.1345/aph.1H679 | s2cid = 25627664 | url = http://www.theannals.com/cgi/content/abstract/aph.1H679v1 | format = abstract | archive-url = https://web.archive.org/web/20070227143703/http://www.theannals.com/cgi/content/abstract/aph.1H679v1 | url-status = dead | archive-date = 27 February 2007 | url-access = subscription }}(published online Jan 2007)</ref> though another meta-analysis published shortly thereafter by researchers from GlaxoSmithKline 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.<ref name="GSK">{{cite journal | vauthors = Kollar C, Schneider H, Waksman J, Krusinska E | title = Meta-analysis of the efficacy of a single dose of phenylephrine 10 mg compared with placebo in adults with acute nasal congestion due to the common cold | journal = Clinical Therapeutics | volume = 29 | issue = 6 | pages = 1057–70 | date = June 2007 | pmid = 17692721 | doi = 10.1016/j.clinthera.2007.05.021 }}</ref> A 2007 study by Wyeth Consumer Healthcare notes that 7 studies available in 1976 support the efficacy of phenylephrine at a 10 mg dosage.<ref name="Desjardins2007">{{cite journal | vauthors = Desjardins PJ, Berlin RG | title = Efficacy of phenylephrine | journal = British Journal of Clinical Pharmacology | volume = 64 | issue = 4 | pages = 555–6; author reply 557 | date = October 2007 | pmid = 17610531 | pmc = 2048561 | doi = 10.1111/j.1365-2125.2007.02935.x }}</ref> The Food and Drug Administration withdrew the indication "for the temporary relief of nasal congestion associated with sinusitis" in 2007.<ref name=AHFS2022/>

Two studies published in 2009 examined the effects of phenylephrine on symptoms of allergic rhinitis by exposing people to pollen in a controlled, indoor environment. Neither study was able to distinguish between the effects of phenylephrine and a placebo. Pseudoephedrine and loratadine–montelukast therapy were found to be significantly more effective than both phenylephrine and placebo.<ref name="danzig09"/><ref name="yao09"/>

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 in the United States 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 restrictions on sales.<ref name="HeraldTribune">{{cite news|date=30 January 2007|title=All stuffed up: Reformulated cold medicines might not be able to do the job|newspaper=Sarasota Herald-Tribune|url=http://www.heraldtribune.com/apps/pbcs.dll/article?AID=/FP/20070130/HEALTHMATTERS/70129001/1025/NEWS06|url-status=dead|access-date=25 April 2023|archive-url=https://web.archive.org/web/20070301095838/http://www.heraldtribune.com/apps/pbcs.dll/article?AID=%2FFP%2F20070130%2FHEALTHMATTERS%2F70129001%2F1025%2FNEWS06|archive-date=1 March 2007|vauthors= Hillenmeyer K}}</ref> Phenylephrine has been off-patent since 1950,<ref name= "patent"/> and many generic brands are available.{{Citation needed|date=June 2020}}

In September 2023, an independent advisory committee to the U.S. Food and Drug Administration (FDA) unanimously agreed that there is insufficient evidence showing that "orally administered phenylephrine is effective as a nasal decongestant".<ref>{{cite web | title=FDA clarifies results of recent AC meeting on oral phenylephrine | website=U.S. Food and Drug Administration (FDA) | date=14 September 2023 | url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-clarifies-results-recent-advisory-committee-meeting-oral-phenylephrine | archive-url=https://web.archive.org/web/20230914174151/https://www.fda.gov/drugs/drug-safety-and-availability/fda-clarifies-results-recent-advisory-committee-meeting-oral-phenylephrine | url-status=dead | archive-date=14 September 2023 | access-date=14 September 2023}}</ref> The committee also unanimously believes that this does not need further study. The FDA responded to the committee, stating it would take its advice under advisement.<ref name="christensen23">{{cite news | vauthors = Christensen J |date=12 September 2023 |title=Popular OTC medicines for colds and allergies don't work, FDA panel says |work=CNN |url=https://www.cnn.com/2023/09/12/health/phenylephrine-tablets-ineffective-fda-panel-says/index.html |access-date=12 September 2023}}</ref><ref>{{Cite web | vauthors = Constantino AK |date=2023-09-12 |title=Decongestant found in many cold, allergy medicines doesn't actually work, FDA advisors say |url=https://www.cnbc.com/2023/09/12/decongestant-phenylephrine-ineffective.html |access-date=2023-09-12 |website=CNBC }}</ref> In November 2024, the FDA proposed to remove oral phenylephrine as an active ingredient that can be used in over-the-counter (OTC) monograph drug products for the temporary relief of nasal congestion.<ref name="FDA PR 20241107" />

=== Hemorrhoids === Hemorrhoids are caused by swollen veins in the rectal area.<ref>{{cite web | url = http://www.mayoclinic.org/diseases-conditions/hemorrhoids/basics/definition/con-20029852 | title = Hemorrhoids | publisher = Mayo Clinic }}</ref> 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 to narrow the swollen veins and relieve the attendant pain. However, veins contain less vascular smooth muscle in their walls than arteries. Products for treatment may also include substances that will form a protective barrier over the inflamed area, resulting in less pain when feces are passed.<ref>{{cite web | url = https://www.webmd.com/drugs/2/drug-76444/phenylephrine-rectal/details |title = Phenylephrine HCl Suppository | work = WebMD | access-date = 4 April 2015 }}</ref>

Phenylephrine hydrochloride at 0.25% is used as a vasoconstrictor in suppository formulations for hemorrhoid treatment.<ref name="Suppository-Label">{{cite web | url = https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a23ded81-78ba-c199-a8f0-aaf360b216ff | work = DailyMed | title = Preparation H – cocoa butter and phenylephrine hydrochloride suppository | publisher = U.S. National Institutes of Health |access-date=4 April 2015}}</ref>

=== Pupil dilation === {{Redirect|Prefrin|the iron supplement|Proferrin}}

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 as a synergist when tropicamide alone is not sufficient. Narrow-angle glaucoma is a contraindication to phenylephrine use. As a mydriatic, it is available in 2.5% and 10% eye drops. Phenylephrine eye drops are applied to the eye after a topical anesthetic is applied.<ref>{{cite web | title = Phenylephrine Hydrochloride Ophthalmic Solution, USP 2.5% — Sterile | url = http://akorn.com/documents/catalog/sell_sheets/17478-205-10.pdf | archive-url = https://web.archive.org/web/20160303234455/http://akorn.com/documents/catalog/sell_sheets/17478-205-10.pdf | archive-date = 3 March 2016 | url-status = dead | publisher = Akorn }}</ref>

=== 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.<ref>{{cite journal | vauthors = Bizrah M, Corbett MC | title = Intracameral Phenylephrine to Arrest Intraoperative Intraocular Bleeding: A New Technique | journal = Ophthalmology and Therapy | volume = 8 | issue = 1 | pages = 137–141 | date = March 2019 | pmid = 30771215 | pmc = 6393249 | doi = 10.1007/s40123-019-0165-y }}</ref>

=== Low blood pressure === Phenylephrine is commonly used as a vasopressor to increase the blood pressure in unstable patients with hypotension (low blood pressure), especially resulting from septic shock.<ref name="MengSunZhao2024" /><ref name="LarsonAndersonThomson2021">{{cite journal | vauthors = Larson S, Anderson L, Thomson S | title = Effect of phenylephrine on cerebral oxygen saturation and cardiac output in adults when used to treat intraoperative hypotension: a systematic review | journal = JBI Evid Synth | volume = 19 | issue = 1 | pages = 34–58 | date = January 2021 | pmid = 32941358 | doi = 10.11124/JBISRIR-D-19-00352 | url = }}</ref> Such use is common in surgery and anesthesia or critical-care practices;<ref name="MengSunZhao2024" /><ref name="LarsonAndersonThomson2021" /> it is especially useful in counteracting the hypotensive effect of epidural and spinal anesthesia, as well as the vasodilating effect of bacterial toxins and the inflammatory response in sepsis and systemic inflammatory response syndrome.

Because of its vasoconstrictive effect, phenylephrine can cause severe necrosis 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.<ref name="Cooper2008">{{cite journal | vauthors = Cooper BE | title = Review and update on inotropes and vasopressors | journal = AACN Advanced Critical Care | volume = 19 | issue = 1 | pages = 5–13; quiz 14–15 | date = 2008 | pmid = 18418098 | doi = 10.1097/01.AACN.0000310743.32298.1d | s2cid = 39192378 }}</ref>

In clinical studies, intravenous phenylephrine increases blood pressure, decreases cardiac output, increases cerebral blood flow, and decreases cerebral tissue oxygen saturation.<ref name="MengSunZhao2024">{{cite journal | vauthors = Meng L, Sun Y, Zhao X, Meng DM, Liu Z, Adams DC, McDonagh DL, Rasmussen M | title = Effects of phenylephrine on systemic and cerebral circulations in humans: a systematic review with mechanistic explanations | journal = Anaesthesia | volume = 79 | issue = 1 | pages = 71–85 | date = January 2024 | pmid = 37948131 | doi = 10.1111/anae.16172 | url = | doi-access = free }}</ref><ref name="LarsonAndersonThomson2021" /> The decreases in cardiac output, increases in cerebral blood flow, and decreases in cerebral tissue oxygen saturation with phenylephrine are all related to the degree of blood pressure increase.<ref name="MengSunZhao2024" /> The decrease in cardiac output is primarily due to a decrease in heart rate and a modest decrease in stroke volume.<ref name="MengSunZhao2024" /> The decrease in heart rate is due to activation of the arterial baroreflex, which regulates heart rate in response to changes in blood pressure.<ref name="MengSunZhao2024" /><ref name="LarsonAndersonThomson2021" /> Because of the decrease in cardiac output, phenylephrine is a negative inotropic agent.<ref name="MengSunZhao2024" /> Its effects on cardiac output and cerebral oxygenation are unfavorable, and on account of this, the use of phenylephrine in the treatment of intraoperative hypotension is now being recommended against and moved away from in favor of other agents without these adverse effects like ephedrine and dopamine.<ref name="MengSunZhao2024" /><ref name="LarsonAndersonThomson2021" />

When taken orally, phenylephrine has a threshold dose of about 50{{nbsp}}mg to affect the cardiovascular system, a dose at which the drug decreases heart rate and slightly increases arterial blood pressure.<ref name="Eccles2007" /> Additionally, an over-the-counter dose of 60{{nbsp}}mg produces a slight increase in heart rate with no detectable changes in blood pressure.<ref name="Eccles2007" /> However, other literature reports that doses over 15{{nbsp}}mg affect the cardiovascular system, including increases in blood pressure and decreases in heart rate.<ref name="AtkinsonPottsAnderson2015" /> Higher doses, like 150{{nbsp}}mg, more robustly affect the cardiovascular system.<ref name="ChuaBenrimojTriggs1989" />

===Other uses=== Phenylephrine has been used in the treatment of postural orthostatic tachycardia syndrome (POTS).<ref name="LyongaNogongeNyange2024">{{cite journal | vauthors = Lyonga Ngonge A, Nyange C, Ghali JK | title = Novel pharmacotherapeutic options for the treatment of postural orthostatic tachycardia syndrome | journal = Expert Opin Pharmacother | volume = 25 | issue = 2 | pages = 181–188 | date = February 2024 | pmid = 38465412 | doi = 10.1080/14656566.2024.2319224 | url = }}</ref> It has been found to improve vascular resistance, enhance circulatory support, and improve symptoms of orthostatic intolerance in people with the condition.<ref name="LyongaNogongeNyange2024" /> It has been described as particularly effective in people with neuropathic POTS.<ref name="LyongaNogongeNyange2024" /> However, phenylephrine has not been specifically approved for the treatment of POTS, and data on this use are limited.<ref name="LyongaNogongeNyange2024" /> This is also the case with other medications used in the treatment of POTS.<ref name="LyongaNogongeNyange2024" />

Phenylephrine has been used in the treatment of priapism. It is also sometimes used as a reversal medication of Trimix injections.<ref name="JiangChristakosFam2014">{{cite journal | vauthors = Jiang P, Christakos A, Fam M, Sadeghi-Nejad H | title = Prophylactic phenylephrine for iatrogenic priapism: a pilot study with Peyronie's patients | journal = Korean J Urol | volume = 55 | issue = 10 | pages = 665–669 | date = October 2014 | pmid = 25324950 | pmc = 4198766 | doi = 10.4111/kju.2014.55.10.665 | url = }}</ref><ref name="MartinCocchio2016">{{cite journal | vauthors = Martin C, Cocchio C | title = Effect of phenylephrine and terbutaline on ischemic priapism: a retrospective review | journal = Am J Emerg Med | volume = 34 | issue = 2 | pages = 222–224 | date = February 2016 | pmid = 26597497 | doi = 10.1016/j.ajem.2015.10.029 | url = }}</ref>

===Available forms=== Phenylephrine is available in the form of oral tablets and syrups for use as a nasal decongestant, as an intravenous solution to treat hypotension, as an ophthalmic solution, spray, or eye drop to cause pupil dilation, and as a cocoa butter suppository, among other forms.<ref name="Drugs@FDA">{{cite web | title=Drugs@FDA: FDA-Approved Drugs | website=accessdata.fda.gov | publisher = Food and Drug Administration | url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm | archive-url=https://web.archive.org/web/20161104020633/http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm | url-status=dead | archive-date=4 November 2016 | access-date=21 July 2024}}</ref><ref name="DailyMed">{{cite web | title=Search Results for phenylephrine | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=phenylephrine&pagesize=200&page=1 | access-date=21 July 2024}}</ref> It was also previously available as a metered aerosol for inhalation, but this formulation was discontinued.<ref name="Drugs@FDA" />

Phenylephrine is available both alone and in combination with other drugs.<ref name="Drugs@FDA" /><ref name="DailyMed" /> These other drugs include antihistamines like chlorpheniramine, doxylamine, promethazine, and mepyramine (pyrilamine); analgesics like paracetamol (acetaminophen), ibuprofen, ketorolac, and codeine; cough suppressants like dextromethorphan; expectorants like guaifenesin; anticholinergics like cyclopentolate and tropicamide; and β-adrenergic receptor agonists like isoprenaline (isoproterenol).<ref name="Drugs@FDA" /><ref name="DailyMed" /> It is used in combination with antihistamines and analgesics in cough and cold preparations, with anticholinergics in ophthalmic formulations, and with β-adrenergic receptor agonists in inhalational forms.<ref name="Drugs@FDA" /><ref name="DailyMed" /> Intravenous phenylephrine is always formulated by itself.<ref name="Drugs@FDA" />

==Contraindications== Phenylephrine is contraindicated in people with hypertension, hyperthyroidism, and heart disease due to its vasoconstrictor effects.<ref name="Eccles2007" /> Relative contraindications include people with Raynaud's syndrome due to vasoconstriction, those taking monoamine oxidase inhibitors (MAOIs) due to inhibition of the metabolism of phenylephrine, and people with prostate problems due to potential exacerbation of urinary retention.<ref name="Eccles2007" /><ref name="JohnsonHricik1993" />

== Side effects == Phenylephrine taken orally at indicated doses is usually well-tolerated.<ref name="AtkinsonPottsAnderson2015" /> It may cause side effects such as headache, reflex bradycardia, excitability, restlessness, and cardiac arrhythmias.<ref name=AHFS2022/> At higher than indicated doses, phenylephrine can increase blood pressure and decrease heart rate.<ref name="AtkinsonPottsAnderson2015" /> A 45{{nbsp}}mg dose of phenylephrine can increase systolic blood pressure by 20{{nbsp}}mmHg.<ref name="AtkinsonPottsAnderson2015" /> Possible side effects of intravenous phenylephrine are dose-dependent and may include bradycardia and reactive hypertension.<ref name="AtkinsonPottsAnderson2015" />

=== Heart === The primary side effect of phenylephrine is high blood pressure. People with high blood pressure are typically advised to avoid products containing it. Because this medication is a sympathomimetic amine without β-adrenergic receptor agonist 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.<ref>{{cite web | url = http://reference.medscape.com/drug/vazculep-phenylephrine-342444 | title = Phenylephrine (Rx) | work = Medscape | access-date = 4 April 2015}}</ref> The low concentration eye drops do not cause blood pressure changes and the changes with the higher dose drops do not last long.<ref name="StavertMcGuinessHarper2015">{{cite journal | vauthors = Stavert B, McGuinness MB, Harper CA, Guymer RH, Finger RP | title = Cardiovascular Adverse Effects of Phenylephrine Eyedrops: A Systematic Review and Meta-analysis | journal = JAMA Ophthalmology | volume = 133 | issue = 6 | pages = 647–652 | date = June 2015 | pmid = 25789577 | doi = 10.1001/jamaophthalmol.2015.0325 | doi-access = free }}</ref>

The cardiovascular effects of phenylephrine may be potentiated in people with hypertension.<ref name="AtkinsonPottsAnderson2015" /> Hypertensive crisis with phenylephrine eye drops has been reported in people with hypertension.<ref name="AtkinsonPottsAnderson2015" /> In people with underlying cardiovascular disease, phenylephrine has been found to increase blood pressure and cause associated impairment in myocardial perfusion.<ref name="AtkinsonPottsAnderson2015" /> Other reported side effects of phenylephrine have included increased blood pressure, vasoconstriction resulting in worsened orthostatic tolerance, atrial fibrillation following coronary artery bypass surgery, decreased cerebral oxygenation, bradycardia in people with spinal cord injury, cardiac arrhythmias, pulmonary edema, myocardial infarction, and microvascular occlusion syndrome.<ref name="AtkinsonPottsAnderson2015" /> Rarely, stroke has been reported with phenylephrine, including in the oral, topical, and intravenous forms.<ref name="AtkinsonPottsAnderson2015" />

Due to the increased risk of side effects in people with hypertension, phenylephrine is not suggested for use in this population.<ref name="IV-Label-1" /><ref name="Eccles2007" />

===Others=== Prostatic hyperplasia can also be worsened by use, and chronic use can lead to rebound hyperemia.<ref name=pharmnemonics>{{Cite book | vauthors = Shen H |title=Illustrated Pharmacology Memory Cards: PharMnemonics|year=2008|publisher=Minireview|isbn=978-1-59541-101-3|page=3}}</ref> 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.<ref name="IV-Label-2">{{cite web | title = Phenylephrine Hydrochloride injection, for intravenous use | url = http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203826s000lbl.pdf | archive-url = https://web.archive.org/web/20141103082217/http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203826s000lbl.pdf | url-status = dead | archive-date = 3 November 2014 | publisher = U.S. Food and Drug Administration }}</ref>

Phenylephrine is pregnancy category C. Due to the lack of studies done in animals and humans, it is unknown whether there is harm to the fetus. Phenylephrine should only be given to pregnant women who have a clear need.<ref name="IV-Label-2"/>

Extended use may cause rhinitis medicamentosa, a condition of rebound nasal congestion.<ref name="nasal">{{cite web|url=https://www.drugs.com/mmx/neo-synephrine-nasal-spray.html|title=Neo-Synephrine Nasal Spray Drug Information, Professional|work=drugs.com|access-date=4 April 2015|archive-date=11 May 2015|archive-url=https://web.archive.org/web/20150511221150/http://www.drugs.com/mmx/neo-synephrine-nasal-spray.html|url-status=dead}}</ref>

== Interactions == Phenylephrine is susceptible to metabolism by monoamine oxidase.<ref name="Eccles2007" /><ref name="AtkinsonPottsAnderson2015">{{cite journal | vauthors = Atkinson HC, Potts AL, Anderson BJ | title = Potential cardiovascular adverse events when phenylephrine is combined with paracetamol: simulation and narrative review | journal = Eur J Clin Pharmacol | volume = 71 | issue = 8 | pages = 931–938 | date = August 2015 | pmid = 26022219 | pmc = 4500855 | doi = 10.1007/s00228-015-1876-1 | url = }}</ref> Because of this, monoamine oxidase inhibitors (MAOIs) can inhibit the metabolism of phenylephrine and increase exposure to the medication.<ref name="Eccles2007" /><ref name="AtkinsonPottsAnderson2015" /> Whereas a 45{{nbsp}}mg oral dose of phenylephrine alone increases systolic blood pressure by 20{{nbsp}}mmHg, use of this dose in people on MAOIs increases systolic blood pressure by more than 60{{nbsp}}mmHg.<ref name="AtkinsonPottsAnderson2015" />

Phenylephrine can interact with other adrenergic drugs, such as beta blockers like propranolol, α1-adrenergic receptor antagonists like chlorpromazine, α2-adrenergic receptor agonists like clonidine, norepinephrine reuptake inhibitors like atomoxetine and amitriptyline, and MAOIs (which increase norepinephrine levels).<ref name="RichardsLopezMaani2023" /> It can also interact with corticosteroids like prednisone, which sensitize the vasculature to sympathomimetics and augment their vasoconstrictive effects, and with ergot alkaloids, which also have vasoconstrictor effects and can have additive or synergistic effects with phenylephrine.<ref name="RichardsLopezMaani2023" /> In addition, combination of phenylephrine with other sympathomimetic drugs can increase pressor effects and the risk of hemorrhagic stroke.<ref name="RichardsLopezMaani2023" /> Other drugs that may decrease the effects of phenylephrine may include calcium channel blockers, ACE inhibitors and benzodiazepines.<ref name="IV-Label-3" /> Patients taking these medications may need a higher dose of phenylephrine to achieve a comparable increase in blood pressure.<ref name="IV-Label-3">{{cite web | url = https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/204300lbl.pdf |title=Vazculep Package Insert | publisher = U.S. Food and Drug Administration }}</ref> Concomitant use of phenylephrine with the preceding agents may necessitate dose adjustments.

Acetaminophen (paracetamol) has been found to increase exposure to oral phenylephrine.<ref name="AtkinsonPottsAnderson2015" /> It more than doubles phenylephrine's bioavailability, reduces its absorption half-time by 50%, increases phenylephrine levels by approximately 2-fold, and increases peak phenylephrine levels by 4-fold, with substantial interindividual variability.<ref name="AtkinsonPottsAnderson2015" /> Phenylephrine is widely formulated with acetaminophen in combination products.<ref name="AtkinsonPottsAnderson2015" /> The combination may increase the cardiovascular effects of phenylephrine.<ref name="AtkinsonPottsAnderson2015" /> The mechanism of the interaction between phenylephrine and acetaminophen is unknown, but it has been suggested that it may be due to saturation of sulfation pathways by acetaminophen that also participates in phenylephrine metabolism.<ref name="AtkinsonPottsAnderson2015" />

== Pharmacology ==

=== Pharmacodynamics === Phenylephrine is a selective agonist of the α1-adrenergic receptor, one of the biological targets of the catecholamine hormones and neurotransmitters epinephrine (adrenaline) and norepinephrine (noradrenaline).<ref name="Eccles2007" /><ref name="RichardsLopezMaani2023" /><ref name="ODonnell1995" /> It is a full agonist of the α1-adrenergic receptor in most assessed tissues.<ref name="Chess-WilliamsWilliamsonBroadley1990">{{cite journal | vauthors = Chess-Williams RG, Williamson KL, Broadley KJ | title = Whether phenylephrine exerts inotropic effects through alpha- or beta-adrenoceptors depends upon the relative receptor populations | journal = Fundam Clin Pharmacol | volume = 4 | issue = 1 | pages = 25–37 | date = 1990 | pmid = 2160415 | doi = 10.1111/j.1472-8206.1990.tb01014.x | url = }}</ref> The drug has weak, minimal, or no agonist activity at the α2-adrenergic receptor or the β-adrenergic receptors.<ref name="Eccles2007" /><ref name="RichardsLopezMaani2023" /><ref name="ODonnell1995" /> At the β-adrenergic receptors, it is a partial agonist.<ref name="Chess-WilliamsWilliamsonBroadley1990" />

Phenylephrine also has relatively little or no activity as a norepinephrine releasing agent.<ref name="Eccles2007" /><ref name="ODonnell1995" /> As such, it has little activity as an indirectly acting sympathomimetic and non-selective activator of adrenergic receptors.<ref name="Eccles2007" /><ref name="ODonnell1995" /> This is in contrast to related sympathomimetics like pseudoephedrine.<ref name="Eccles2007" /> However, more recent research suggests that phenylephrine may actually be more potent as a norepinephrine releasing agent than has previously been thought.<ref name="Al-KhrasaniKaradiGalambos2022">{{cite journal | vauthors = Al-Khrasani M, Karadi DA, Galambos AR, Sperlagh B, Vizi ES | title = The Pharmacological Effects of Phenylephrine are Indirect, Mediated by Noradrenaline Release from the Cytoplasm | journal = Neurochem Res | volume = 47 | issue = 11 | pages = 3272–3284 | date = November 2022 | pmid = 35945308 | pmc = 9546997 | doi = 10.1007/s11064-022-03681-2 | url = }}</ref> This might help to explain certain unexpected pharmacodynamic effects of the drug.<ref name="Al-KhrasaniKaradiGalambos2022" />

Because of its α1-adrenergic receptor agonism, phenylephrine is a directly acting sympathomimetic vasoconstrictor<ref name="Eccles2007" /><ref name="ODonnell1995">{{cite journal | vauthors = O'Donnell SR | title = Sympathomimetic vasoconstrictors as nasal decongestants | journal = Med J Aust | volume = 162 | issue = 5 | pages = 264–267 | date = March 1995 | pmid = 7534374 | doi = 10.5694/j.1326-5377.1995.tb139882.x | url = }}</ref> and produces both venous and arterial vasoconstriction.<ref name="IV-Label-1">{{cite web | url = https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=72348406-e74f-46c5-b93d-34d07cffe1fd | title = Phenylephrine hydrochloride injection |work=DailyMed | publisher = U.S. National Institutes of Health |access-date=4 April 2015}}</ref><ref name="RichardsLopezMaani2023" /> The term ''sympathomimetic'' means that it mimics the actions of epinephrine or norepinephrine.<ref name="CostaGrandoMilandri2022" />

Phenylephrine works as a nasal decongestant by causing local vasoconstriction in the nose.<ref name="ODonnell1995" /> Whereas the related sympathomimetic decongestant pseudoephedrine causes both vasoconstriction and increase of mucociliary clearance through its non-specific adrenergic activity, phenylephrine's selective α1-adrenergic receptor agonism causes vasoconstriction alone, resulting in a difference in their methods of action.{{Citation needed|date=June 2020}}

===Pharmacokinetics===

====Absorption==== Phenylephrine is rapidly absorbed from the gastrointestinal tract when taken orally.<ref name="Eccles2007" /> However, its absorption is incomplete and erratic.<ref name="ChuaBenrimojTriggs1989">{{cite journal | vauthors = Chua SS, Benrimoj SI, Triggs EJ | title = Pharmacokinetics of non-prescription sympathomimetic agents | journal = Biopharm Drug Dispos | volume = 10 | issue = 1 | pages = 1–14 | date = 1989 | pmid = 2647163 | doi = 10.1002/bdd.2510100102 | url = }}</ref> Because of extensive first-pass metabolism, phenylephrine has an oral bioavailability of only about 38% relative to intravenous administration.<ref name="Eccles2007" /><ref name="DrugBank" /><ref name="ChuaBenrimojTriggs1989" /><ref name="Medsafe2004">{{cite web|orig-date=25 November 2004|date=23 May 2013|title=Recommendation on phenylephrine|url=https://www.medsafe.govt.nz/profs/class/Minutes/2001-2005/mccMin25Nov2004.htm|publisher=Medsafe|access-date=25 April 2023}}</ref> However, another source has stated that the bioavailability of phenylephrine is poorly documented and may actually be as low as 0.003%.<ref name="AtkinsonPottsAnderson2015" /> The time to peak concentrations is 1.0 to 1.3{{nbsp}}hours.<ref name="Eccles2007" />

====Distribution==== The steady-state volume of distribution of phenylephrine is 340{{nbsp}}L.<ref name="RichardsLopezMaani2023" />

Phenylephrine does not cross the blood–brain barrier and hence is a peripherally selective drug with no central nervous system activity.<ref name="MengSunZhao2024" /><ref name="LarsonAndersonThomson2021" /><ref name="Eccles2007" /><ref name="ODonnell1995" /> Its lack of blood-brain barrier permeability is related to its hydroxyl groups and high hydrophilicity.<ref name="Eccles2007" /><ref name="JohnsonHricik1993" /> The lack of central permeation with phenylephrine is in contrast to certain other related decongestant and sympathomimetic agents like pseudoephedrine, ephedrine, and phenylpropanolamine.<ref name="JohnsonHricik1993" /><ref name="Eccles2007" /><ref name="ODonnell1995" />

====Metabolism==== Phenylephrine is metabolized in the intestines and liver prior to reaching the systemic circulation when taken orally.<ref name="Eccles2007" /> It is extensively metabolized during first-pass metabolism due to susceptibility to monoamine oxidases, similarly to epinephrine.<ref name="Eccles2007" /><ref name="RichardsLopezMaani2023" /><ref name="DrugBank" /><ref name="ChuaBenrimojTriggs1989" /> Phenylephrine is metabolized via oxidative deamination by both MAO-A and MAO-B.<ref name="RichardsLopezMaani2023" /><ref name="DrugBank" /><ref name="ChuaBenrimojTriggs1989" /> In contrast to epinephrine and norepinephrine, phenylephrine is not a catecholamine, and is not metabolized by catechol O-methyltransferase (COMT).<ref name="ODonnell1995" /> Besides monoamine oxidase, phenylephrine is also metabolized by sulfation and glucuronidation conjugation.<ref name="RichardsLopezMaani2023" /><ref name="DrugBank" /> Non-oral routes of phenylephrine, like intranasal, ophthalmic, and parenteral, do not undergo first-pass metabolism in the gastrointestinal tract.<ref name="ChuaBenrimojTriggs1989" />

The major metabolite of phenylephrine is [https://pubchem.ncbi.nlm.nih.gov/compound/3-Hydroxymandelic-acid ''meta''-hydroxymandelic acid], which is inactive.<ref name="DrugBank" /><ref name="ChuaBenrimojTriggs1989" /> Lesser metabolites of phenylephrine include sulfate and glucuronide conjugates, which are also inactive.<ref name="DrugBank" /><ref name="ChuaBenrimojTriggs1989" />

Unlike phenylephrine, related sympathomimetics with a methyl group at the α carbon (i.e., amphetamines), like ephedrine, pseudoephedrine, phenylpropanolamine, methoxamine, and methoxyphenamine, are resistant to degradation by monoamine oxidase.<ref name="ChuaBenrimojTriggs1989" />

====Elimination==== Phenylephrine is primarily excreted in urine.<ref name="RichardsLopezMaani2023" /><ref name="DrugBank" /> It is recovered 86% in urine.<ref name="DrugBank" /> The drug is excreted in urine 3 to 16% unchanged, 57% as [https://pubchem.ncbi.nlm.nih.gov/compound/3-Hydroxymandelic-acid ''meta''-hydroxymandelic acid], and 8% as sulfate conjugates.<ref name="Eccles2007" /><ref name="DrugBank" /> Glucuronide conjugates constitute a smaller portion of phenylephrine.<ref name="ChuaBenrimojTriggs1989" />

Phenylephrine has a relatively short elimination half-life of 2.0 to 3.0{{nbsp}}hours regardless of route of administration.<ref name="Eccles2007" /><ref name="RichardsLopezMaani2023" /><ref name="DrugBank" /><ref name="KanferDowseVuma1993">{{cite journal | vauthors = Kanfer I, Dowse R, Vuma V | title = Pharmacokinetics of oral decongestants | journal = Pharmacotherapy | volume = 13 | issue = 6 Pt 2 | pages = 116S–128S; discussion 143S–146S | year = 1993 | pmid = 7507589 | doi = 10.1002/j.1875-9114.1993.tb02780.x | s2cid = 23528004 }}</ref><ref name="ChuaBenrimojTriggs1989" /> Its lack of metabolism by COMT is said to be responsible for its much longer duration of action than related agents like norepinephrine.<ref name="ODonnell1995" />

==Chemistry== Phenylephrine is a substituted phenethylamine and can also be referred to structurally as (''R'')-β,3-dihydroxy-''N''-methylphenethylamine.<ref name="Elks2014" /><ref name="PubChem" /><ref name="DrugBank" /> It is closely structurally related to epinephrine (adrenaline; 3,4,β-trihydroxy-''N''-methylphenethylamine), differing from it only in the absence of one hydroxyl group on the phenyl ring.<ref name="Eccles2007">{{cite journal | vauthors = Eccles R | title = Substitution of phenylephrine for pseudoephedrine as a nasal decongeststant. An illogical way to control methamphetamine abuse | journal = Br J Clin Pharmacol | volume = 63 | issue = 1 | pages = 10–14 | date = January 2007 | pmid = 17116124 | pmc = 2000711 | doi = 10.1111/j.1365-2125.2006.02833.x | url = | quote = PE and PDE are sympathomimetic vasoconstrictors that are closely related to adrenaline in structure, as illustrated in Figure 1. PE differs chemically from adrenaline only in the absence of one hydroxyl group from the benzene ring. [...] PE is a relatively selective α1 agonist. It has weak α2 adrenoceptor agonist activity and low β-agonist activity. Most of the α1 agonist activity is due to a direct action on α receptors with relatively little indirect effect via noradrenaline release [11].}}</ref> It is a chiral compound and is used as the enantiopure (''R'')-stereoisomer.<ref name="KanferDowseVuma1993" /><ref name="Elks2014" /> The racemic form has not been formally named or used.<ref name="Elks2014" />

Phenylephrine is the ''N''-methylated derivative of norfenefrine (3,β-dihydroxyphenethylamine).<ref name="Elks2014" /> The racemic ''N''-ethyl analogue is etilefrine (ethylphenephrine).<ref name="Elks2014" /> Synephrine (''p''-synephrine, oxedrine; 4,β-dihydroxyphenethylamine) is a positional isomer of phenylephrine.<ref name="CostaGrandoMilandri2022">{{cite journal | vauthors = Costa VM, Grando LG, Milandri E, Nardi J, Teixeira P, Mladěnka P, Remião F | title = Natural Sympathomimetic Drugs: From Pharmacology to Toxicology | journal = Biomolecules | volume = 12 | issue = 12 | date = November 2022 | page = 1793 | pmid = 36551221 | pmc = 9775352 | doi = 10.3390/biom12121793 | doi-access = free | url = }}</ref> In contrast to epinephrine and norepinephrine (noradrenaline; 3,4,β-trihydroxyphenethylamine), phenylephrine is not a catecholamine since it does not have two hydroxyl groups on its phenyl ring.<ref name="ODonnell1995" /> Besides the catecholamines, the chemical structure of phenylephrine somewhat resembles that of amphetamine (α-methylphenethylamine).<ref name="JohnsonHricik1993">{{cite journal | vauthors = Johnson DA, Hricik JG | title = The pharmacology of α-adrenergic decongestants | journal = Pharmacotherapy | volume = 13 | issue = 6 Pt 2 | pages = 110S–115S; discussion 143S–146S | date = 1993 | pmid = 7507588 | doi = 10.1002/j.1875-9114.1993.tb02779.x| url = }}</ref> However, phenylephrine does not have a methyl group at the α carbon and hence is not an amphetamine itself.<ref name="JohnsonHricik1993" />

Phenylephrine is a small-molecule compound with the molecular formula C9H13NO2 and a molecular weight of 167.205{{nbsp}}g/mol.<ref name="PubChem" /><ref name="DrugBank" /> It is a highly hydrophilic compound, with an experimental log P of -0.3.<ref name="Xiao2020">{{cite book | vauthors = Xiao K | title=Analytical Scientists in Pharmaceutical Product Development: Task Management and Practical Knowledge | publisher=Wiley | year=2020 | isbn=978-1-119-54782-2 | url=https://books.google.com/books?id=-xH6DwAAQBAJ&pg=PA122 | access-date=21 July 2024 | page=122 | quote = Second, having multiple polar groups on its molecular structure makes phenylephrine like to interact with water molecules as well. Indeed, the log P (Octanol/Water Partition Coefficient) value of phenylephrine is —0.3, which shows the strong hydrophilicity of this molecule.}}</ref><ref name="PubChem">{{cite web | title=Phenylephrine | website=PubChem | url=https://pubchem.ncbi.nlm.nih.gov/compound/6041 | access-date=21 July 2024}}</ref><ref name="DrugBank">{{cite web | title=Phenylephrine: Uses, Interactions, Mechanism of Action | website=DrugBank Online | date=25 November 2022 | url=https://go.drugbank.com/drugs/DB00388 | access-date=21 July 2024}}</ref> Phenylephrine is used medically almost always as the hydrochloride salt.<ref name="IndexNominum2000" /><ref name="Elks2014" /> However, the free base form and the tannate salt have also been used pharmaceutically to a much lesser extent.<ref name="IndexNominum2000" />

Pivenfrine is the 3-pivalate ester of phenylephrine and has much greater lipophilicity in comparison.<ref name="Elks2014" /><ref name="PubChem-Pivenfrine">{{cite web | title=Pivenfrine | website=PubChem | url=https://pubchem.ncbi.nlm.nih.gov/compound/130545 | access-date=1 September 2024}}</ref>

==History== Phenylephrine was first patented in 1927 and was first introduced for medical use in 1938.<ref name="DeolAlvarezElrabi2023">{{cite journal | vauthors = Deol N, Alvarez G, Elrabi O, Chen G, Ferraro N | title = A comparative review of epinephrine and phenylephrine as vasoconstrictors in dental anesthesia: exploring the factors behind epinephrine's prevalence in the US | journal = J Dent Anesth Pain Med | volume = 23 | issue = 6 | pages = 293–302 | date = December 2023 | pmid = 38076507 | pmc = 10703557 | doi = 10.17245/jdapm.2023.23.6.293 | url = | quote = Phenylephrine, a synthetic selective alpha-1 adrenergic agonist, first received its patent in 1927 and was introduced for medical use in 1938 [8].}}</ref>

==Society and culture==

===Names=== Phenylephrine is the generic name of the drug and its {{Abbrlink|INN|International Nonproprietary Name}}, {{Abbrlink|BAN|British Approved Name}}, and {{Abbrlink|DCF|Dénomination Commune Française}}, while its {{Abbrlink|USAN|United States Adopted Name}} and {{Abbrlink|BANM|British Approved Name}} in the case of the hydrochloride salt are phenylephrine hydrochloride.<ref name="Elks2014">{{cite book | vauthors = Elks J | title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies | publisher=Springer US | year=2014 | isbn=978-1-4757-2085-3 | url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA61 | access-date=22 July 2024 | pages=61,1001}}</ref><ref name="IndexNominum2000">{{cite book | author=Schweizerischer Apotheker-Verein | title=Index Nominum 2000: International Drug Directory | publisher=Medpharm Scientific Publishers | year=2000 | isbn=978-3-88763-075-1 | url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA826 | access-date=22 July 2024 | page=826}}</ref><ref name="MortonHall2012">{{cite book | vauthors = Morton IK, Hall JM | title=Concise Dictionary of Pharmacological Agents: Properties and Synonyms | publisher=Springer Netherlands | year=2012 | isbn=978-94-011-4439-1 | url=https://books.google.com/books?id=tsjrCAAAQBAJ&pg=PA219 | access-date=22 July 2024 | page=219}}</ref><ref name="Drugs.com-International" /> Synonyms of phenylephrine include phenephrine, fenefrine, L-m-synephrine, metaoxedrine, neo-oxedrine, mesatonum, neosynephrine, and m-sympatol.<ref name="Elks2014" /><ref name="IndexNominum2000" /><ref name="Drugs.com-International" /> Brand names of phenylephrine include Neosynephrine or Neo-Synephrine and Sudafed PE, among numerous others.<ref name="Elks2014" /><ref name="IndexNominum2000" /><ref name="DrugBank" /><ref name="Drugs.com-International" /> It is sometimes referred to as simply "neo," an abbreviation of the trade name Neo-Synephrine, especially in critical care settings.<ref>{{Cite journal |date=Apr 2013 |title=ISMP Medication error report analysis |journal=Hospital Pharmacy |volume=48 |issue=4 |pages=267–269 |doi=10.1310/hpj4804-267 |issn=0018-5787 |pmc=3839452 |pmid=24421473 }}</ref>

===Availability=== Phenylephrine is available worldwide as a prescription drug in many different formulations.<ref name="Drugs.com-International">{{cite web | title=Phenylephrine (International database) | website=Drugs.com | date=7 July 2024 | url=https://www.drugs.com/international/phenylephrine.html | access-date=22 July 2024}}</ref>

==Research== ===Hair loss=== Topical phenylephrine has been studied in the treatment of alopecia (hair loss).<ref name="AfifiOparaugoHogeling2021">{{cite journal | vauthors = Afifi L, Oparaugo NC, Hogeling M | title = Review of traction alopecia in the pediatric patient: Diagnosis, prevention, and management | journal = Pediatr Dermatol | volume = 38 Suppl 2 | issue = | pages = 42–48 | date = November 2021 | pmid = 34467569 | doi = 10.1111/pde.14773 | url = | quote = Topical alpha-1 agonist treatment has been investigated as a potential protective treatment from traction on the hair follicle. The arrector pili muscle of the hair follicle expresses α1 adrenergic receptors (α1-AR) which when stimulated results in contraction and erection of the hair follicle.37 It is hypothesized the use of a α1-AR agonist and subsequent contraction would increase the threshold of force required to pull on the hair. In a blinded study of 15 adult patients using topical phenylephrine, 80% of subjects demonstrated reduced shedding with the use of topical phenylephrine and an average reduction in hair loss of approximately 42%. In addition, testing of the force threshold required for epilation demonstrated a 172% increase following topical phenylephrine application.38}}</ref><ref name="GorenShapiroSinclair2016">{{cite journal | vauthors = Goren A, Shapiro J, Sinclair R, Kovacevic M, McCoy J | title = α1-AR agonist induced piloerection protects against the development of traction alopecia | journal = Dermatol Ther | volume = 29 | issue = 3 | pages = 160–163 | date = May 2016 | pmid = 26678522 | doi = 10.1111/dth.12324 | url = }}</ref> It has been found to cause contraction of arrector pili muscles (hair erector muscles), thereby increasing the force required to pluck hair and reducing hair shedding during brushing.<ref name="AfifiOparaugoHogeling2021" /><ref name="GorenShapiroSinclair2016" /> A topical combination of phenylephrine, synephrine, and tyramine, with the code name DA-007, is under formal development for the treatment of alopecia.<ref name="AdisInsight-DA-007">{{Cite web|url=https://adisinsight.springer.com/drugs/800080950|title=DA 007 - AdisInsight|website=adisinsight.springer.com}}</ref><ref name="MedPath">{{cite web | title=DA-007 Advanced Drug Monograph | website=MedPath | date=10 June 2025 | url=https://trial.medpath.com/drug/report/f9e549dc10e2729a | access-date=13 March 2026 | quote = DA-007 is an investigational small molecule drug, formulated as a topical solution, currently under development by Applied Biology Inc. It is a combination of three alpha 1 (α1 ) adrenergic receptor agonists: Phenylephrine, Tyramine, and Synephrine.[3] The primary therapeutic goal of DA-007 is the prevention of Chemotherapy-Induced Alopecia (CIA), a common and distressing side effect of many cancer treatments, particularly in female breast cancer patients undergoing taxane and/or anthracycline-based chemotherapy regimens.[3] The mechanism of action of DA-007 is based on inducing localized vasoconstriction in the scalp. By activating α1-adrenergic receptors on the scalp vasculature, DA-007 aims to reduce local blood perfusion, thereby limiting the delivery of cytotoxic chemotherapeutic agents to the rapidly dividing cells of the hair follicles.[5] This targeted pharmacological approach offers a potential alternative to physical methods like scalp cooling, potentially providing improved convenience and tolerability for patients. The selection of a multi-component formulation suggests a strategy to achieve a more}}</ref>

==References== {{Reflist}}

{{Cardiac stimulants excluding cardiac glycosides}} {{Nasal preparations}} {{Mydriatics and cycloplegics}} {{Adrenergic receptor modulators}} {{Monoamine releasing agents}} {{Phenethylamines}} {{Portal bar | Medicine}}

Category:Alpha1-adrenergic agonists Category:Secondary amines Category:Antihypotensive agents Category:Cardiac stimulants Category:Norepinephrine releasing agents Category:Ophthalmology drugs Category:Peripherally selective drugs Category:3-Hydroxyphenyl compounds Category:Phenylethanolamines Category:Rhinology Category:Sympathomimetics Category:Topical decongestants Category:Vasoconstrictors Category:Wikipedia medicine articles ready to translate Category:Over-the-counter drugs in the United States