Phenylephrine

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Phenylephrine hydrochloride
)

Phenylephrine
Skeletal formula of phenylephrine
Ball-and-stick model of the phenylephrine molecule
Clinical data
Pronunciation/ˌfɛnəlˈɛfriːn, fiː-, -ɪn/
Trade namesNeo-synephrine, others[1]
AHFS/Drugs.comMonograph
License data
intramuscular
ATC code
Legal status
Legal status
  • AU: S2 (Pharmacy medicine)
  • UK:
    General sales list
    (GSL, OTC)
  • US: OTC / Rx-only
Pharmacokinetic data
Bioavailability38% through GI tract
Protein binding95%
MetabolismLiver (oxidative deamination)
Onset of actionVery rapid (IV); within 20 min (by mouth)[2]
Elimination half-life2.1–3.4 h
Duration of actionUp to 20 min (IV); 4 hrs (by mouth)[2]
Identifiers
  • (R)-3-[-1-hydroxy-2-(methylamino)ethyl]phenol
JSmol)
  • O[C@H](c1cc(O)ccc1)CNC
  • InChI=1S/C9H13NO2/c1-10-6-9(12)7-3-2-4-8(11)5-7/h2-5,9-12H,6H2,1H3/t9-/m0/s1 checkY
  • Key:SONNWYBIRXJNDC-VIFPVBQESA-N checkY
  (verify)

Phenylephrine is a

applied to the skin.[2]

Common side effects when taken by mouth or injected include nausea, vomiting, headache, and anxiety.

veins.[2]

Phenylephrine was patented in 1933

generic medication.[4][7][8] Unlike pseudoephedrine, abuse of phenylephrine is very uncommon.[9] Its effectiveness as a nasal decongestant has been questioned.[2][10][11] In 2023, a Food and Drug Administration panel concluded that the drug was ineffective as a nasal decongestant when taken orally.[12]

Medical uses

Decongestant

Phenylephrine is used as an alternative to pseudoephedrine as a decongestant, whose availability has been restricted in some countries due to a potential for use in the illicit synthesis of methamphetamine.[13] 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.[14][15][16]

A 2007 meta-analysis concluded that the evidence for its effectiveness is insufficient,

Wyeth Consumer Healthcare notes that 7 studies available in 1976 support the efficacy of phenylephrine at a 10 mg dosage.[19] The Food and Drug Administration withdrew the indication "for the temporary relief of nasal congestion associated with sinusitis" in 2007.[2]

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 or a placebo. Pseudoephedrine and loratadine–montelukast therapy were found to be significantly more effective than both phenylephrine and placebo.[14][15]

Pseudoephedrine was previously much more commonly available in the United States, however, provisions of the Combat Methamphetamine Epidemic Act of 2005 placed restrictions on 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 the restrictions on sales.[20] Phenylephrine has been off-patent for some time,[when?] and many generic brands are available.[citation needed]

In September 2023, an independent advisory committee to the US Food and Drug Administration (FDA) unanimously agreed that there is insufficient evidence showing that "orally administered phenylephrine is effective as a nasal decongestant".[21] 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.[22][23]

Hemorrhoids

rectal area.[24] 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.[25]

Phenylephrine hydrochloride at 0.25% is used as a vasoconstrictor in suppository formulations for hemorrhoid treatment.[26]

Pupil dilation

"Prefrin" redirects here. For the iron supplement, see
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% minims. Phenylephrine eye drops are applied to the eye after a topical anesthetic is applied.[27]

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.[28]

Vasopressor

Phenylephrine is commonly used as a

spinal anesthesia, as well as the vasodilating effect of bacterial toxins and the inflammatory response in sepsis and systemic inflammatory response syndrome. The elimination half life of phenylephrine is about 2.5 to 3.0 hours.[29]

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.[30]

Side effects

Phenylephrine may cause side effects such as headache, reflex bradycardia, excitability, restlessness and cardiac arrhythmias.[2] Phenylephrine is not suggested for use in people with hypertension.[31]

Heart

The primary side effect of phenylephrine is

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.[32] The low concentration eye drops do not cause blood pressure changes and the changes with the higher dose drops do not last long.[33]

Other

hyperemia.[34] 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.[35]

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.[35]

Extended use may cause rhinitis medicamentosa, a condition of rebound nasal congestion.[36]

Interactions

The increase in blood pressure effect of phenylephrine may be increased by drugs such as monoamine oxidase inhibitors, tricyclic antidepressants, and hydrocortisone. 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

ACE inhibitors and benzodiazepines. Patients taking these medications may need a higher dose of phenylephrine to achieve a comparable increase in blood pressure.[37]

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 α1-adrenergic receptors which causes venous and arterial vasoconstriction.[31][38]

Whereas 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, creating a difference in their methods of action.[citation needed]

Pharmacokinetics

Oral phenylephrine is extensively metabolized by monoamine oxidase,[1] an enzyme that is present on the mitochondrial membrane of cells throughout the body.[39] Compared to oral pseudoephedrine, phenylephrine has a reduced and variable bioavailability; only up to 38%.[1][40]

References

  1. ^ a b c "Phenylephrine (DB00388)". DrugBank. Retrieved 4 April 2015.
  2. ^ a b c d e f g h i j k l "Phenylephrine Monograph for Professionals". Drugs.com. AHFS. 2 March 2022. Retrieved 9 May 2022. However, efficacy of oral phenylephrine for this use [as a decongestant] has been questioned.
  3. ^
    PMID 30521222
    . Retrieved 27 April 2023.
  4. ^
    OCLC 1021215075
    .
  5. ^ U.S. patent 1,932,347, application 1928, expired 1950
  6. ISBN 9783527607495
    .
  7. ^ "Competitive Generic Therapy Approvals". U.S. Food and Drug Administration (FDA). 29 June 2023. Archived from the original on 29 June 2023. Retrieved 29 June 2023.
  8. ^ "First Generic Drug Approvals 2023". U.S. Food and Drug Administration (FDA). 30 May 2023. Archived from the original on 30 June 2023. Retrieved 30 June 2023.
  9. ^ "Max Strength Decongestant Tablets" (PDF). www.mhra.gov.uk. p. 10. Archived from the original (PDF) on 19 August 2019. Retrieved 10 January 2019.
  10. S2CID 247712448
    .
  11. ^ Lowe D (March 2022). "The Uselessness of Phenylephrine". Science (blog).
  12. ^ Christensen J (12 September 2023). "Popular OTC medicines for colds and allergies don't work, FDA panel says". CNN. Retrieved 8 October 2023.
  13. S2CID 13660478
    .
  14. ^
    PMID 19230461
    . Phenylephrine was not significantly different from placebo in the primary end point.
  15. ^
    PMID 19441605
    . There were no statistically significant differences between phenylephrine and placebo for any measures.
  16. PMID 16815167
    .
  17. S2CID 25627664. Archived from the original
    (abstract) on 27 February 2007.(published online Jan 2007)
  18. PMID 17692721
    .
  19. PMID 17610531
    .
  20. Sarasota Herald-Tribune. Archived from the original
    on 1 March 2007. Retrieved 25 April 2023.
  21. ^ "FDA clarifies results of recent AC meeting on oral phenylephrine". U.S. Food and Drug Administration (FDA). 14 September 2023. Retrieved 14 September 2023.
  22. ^ Christensen J (12 September 2023). "Popular OTC medicines for colds and allergies don't work, FDA panel says". CNN. Retrieved 12 September 2023.
  23. ^ Constantino AK (12 September 2023). "Decongestant found in many cold, allergy medicines doesn't actually work, FDA advisors say". CNBC. Retrieved 12 September 2023.
  24. ^ "Hemorrhoids". Mayo Clinic.
  25. ^ "Phenylephrine rectal". WebMD. Retrieved 4 April 2015.
  26. ^ "Preparation H – cocoa butter and phenylephrine hydrochloride suppository". DailyMed. U.S. National Institutes of Health. Retrieved 4 April 2015.
  27. ^ "Phenylephrine Hydrochloride Ophthalmic Solution, USP 2.5% — Sterile" (PDF). Akorn. Archived from the original (PDF) on 3 March 2016.
  28. PMID 30771215
    .
  29. S2CID 23528004
    .
  30. S2CID 39192378
    .
  31. ^ a b "Phenylephrine hydrochloride injection". DailyMed. U.S. National Institutes of Health. Retrieved 4 April 2015.
  32. ^ "Phenylephrine (Rx)". Medscape. Retrieved 4 April 2015.
  33. PMID 25789577
    .
  34. ISBN 978-1-59541-101-3
    .
  35. ^ a b "Phenylephrine Hydrochloride injection, for intravenous use" (PDF). U.S. Food and Drug Administration.
  36. ^ "Neo-Synephrine Nasal Spray Drug Information, Professional". drugs.com. Archived from the original on 11 May 2015. Retrieved 4 April 2015.
  37. ^ "Vazculep Package Insert" (PDF). U.S. Food and Drug Administration.
  38. PMID 30521222
    .
  39. PMID 15279563
    .
  40. ^ "Recommendation on phenylephrine". Medsafe. 23 May 2013 [25 November 2004]. Retrieved 25 April 2023.
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