Phenylephrine

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Phenylephrine
Phenylephrine.png
Phenylephrine3D.png
Systematic (IUPAC) name
(R)-3-[-1-hydroxy-2-(methylamino)ethyl]phenol
Clinical data
AHFS/Drugs.com monograph
MedlinePlus a606008
Pregnancy cat. B2 (AU) C (US)
Legal status GSL (UK) OTC (US)
Routes Oral, intranasal, ophthalmic, intravenous, intramuscular
Pharmacokinetic data
Bioavailability 38% through GI tract
Protein binding 95%
Metabolism Hepatic (monoamine oxidase)
Half-life 2.1–3.4 h
Identifiers
CAS number 59-42-7 YesY
61-76-7 (hydrochloride)
ATC code C01CA06 R01AA04, R01AB01 (combinations), R01BA03, S01FB01, S01GA05
PubChem CID 6041
IUPHAR ligand 485
DrugBank DB00388
ChemSpider 5818 YesY
UNII 1WS297W6MV YesY
KEGG D08365 YesY
ChEBI CHEBI:8093 YesY
ChEMBL CHEMBL1215 YesY
Chemical data
Formula C9H13NO2 
Mol. mass 167.205 g/mol
 YesY (what is this?)  (verify)

Phenylephrine is a selective α1-adrenergic receptor agonist used primarily as a decongestant, as an agent to dilate the pupil, and to increase blood pressure. Phenylephrine is marketed as a substitute for the decongestant pseudoephedrine, though clinical studies differ regarding its effectiveness in this role.

Uses[edit]

Decongestant[edit]

Phenylephrine is used as a decongestant sold as an oral medicine, as a nasal spray, or as eye drops. It is now the most common over-the-counter decongestant in the United States; oxymetazoline is a more common nasal spray.

Oral phenylephrine is extensively metabolised by monoamine oxidase,[1] an enzyme that is present in the intestinal wall and in the liver. Compared to intravenous pseudoephedrine, it has a reduced and variable bioavailability; only up to 38%.[1][2] Because phenylephrine is a selective α-adrenergic receptor agonist, it does not cause the release of endogenous noradrenaline or increase the rate (chronotropy) and strength (inotropy) of heart contractions as pseudoephedrine does.[3] Phenylephrine may cause side effects such as headache, reflex bradycardia, excitability, restlessness and cardiac arrhythmias.[4]

Phenylephrine is used as a replacement 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 multiple studies not being able to come to an agreement. 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.

As a nasal spray, phenylephrine is available in 1% and 0.5% concentrations. It may cause rebound congestion, similar to oxymetazoline.

Hemorrhoid discomfort[edit]

This medication is used to temporarily relieve swelling, burning, pain, and itching caused by hemorrhoids. It works by temporarily narrowing the blood vessels in the area. This effect decreases swelling and discomfort. Some products may also contain substances (e.g., cocoa butter, hard fat, mineral oil, shark liver oil) that form a protective barrier to prevent too much irritating contact with stool.[5]

Mydriatic[edit]

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.[citation needed]

Vasopressor[edit]

Phenylephrine is commonly used as a vasopressor to increase the blood pressure in unstable patients with hypotension, 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 and subarachnoid anesthetics, as well as the vasodilating effect of bacterial toxins and the inflammatory response in sepsis and systemic inflammatory response syndrome. It has the advantage of not being inotropic or chronotropic, so it strictly elevates the blood pressure without increasing the heart rate or contractility (reflex bradycardia may result from the blood pressure increase, however). This is especially useful if the heart is already tachycardic and/or has a cardiomyopathy. The elimination half life of phenylephrine is about 2.5 to 3.0 hours.[citation needed]

Because of its vasoconstrictive effect, phenylephrine (Neo-Synephrine) 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.[6]

Phenylephrine hydrochloride at 0.25% is used as a vasoconstrictor in some suppository formulations.[citation needed]

Detumescent[edit]

Phenylephrine is used by urologists to abort priapism. It is diluted significantly and injected directly into the corpora cavernosa. The mechanism of action is to cause constriction of the blood vessels entering into the penis, thus breaking the pathophysiologic cycle that continues the priapism.[citation needed]

Side effects[edit]

The primary side effect of phenylephrine is hypertension. Patients with hypertension are typically advised to avoid products containing it. Prostatic hyperplasia can also be symptomatically worsened by use, and chronic use can lead to rebound hyperemia.[7] Patients with a history of anxiety disease or panic disorder, or epilepsy and on anticonvulsant medication, 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.[citation needed]

Because this medication is a sympathomimetic amine, it can also increase contractility force and increase output to the cardiac muscle. In other words, phenylephrine mimics norepinephrine binding to α-adrenoreceptors and can cause increased heart rate.

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

Substitute for pseudoephedrine[edit]

Pseudoephedrine and phenylephrine are both used as decongestants; and, until recently, pseudoephedrine was much more commonly available in the United States. This has changed because provisions of the Combat Methamphetamine Epidemic Act of 2005 placed restrictions on the sale of pseudoephedrine products to prevent the clandestine manufacture of methamphetamine. Since 2004, phenylephrine has been increasingly marketed as a substitute for pseudoephedrine; some manufacturers have changed the active ingredients of products to avoid the restrictions on sales.[8] Phenylephrine has been off patent for some time, and many generic brands are available.

Questions about effectiveness[edit]

Pharmacists Leslie Hendeles and Randy Hatton of the University of Florida suggested in 2006 that oral phenylephrine is ineffective as a decongestant at the 10-mg dose used, arguing that the studies used for the regulatory approval of the drug in the United States in 1976 were inadequate to prove effectiveness at the 10-mg dose, and safety at higher doses.[9] Other pharmacists have expressed concerns over phenylephrine's effectiveness as a nasal decongestant,[10] and other clinicians have indicated concern for regulatory actions that reduced the availability of pseudoephedrine.[11][12] A subsequent meta-analysis by the same researchers concluded that the evidence for its effectiveness is insufficient,[13] though another meta-analysis published shortly thereafter by researchers from GlaxoSmithKline found the standard 10-mg dose to be significantly more effective than a placebo.[14] Additionally, two studies published in 2009 examined the effects of phenylephrine on symptoms of allergic rhinitis by exposing sufferers to pollen in a controlled, indoor environment. Neither study was able to distinguish between the effects of phenylephrine or a placebo.[15][16] Pseudoephedrine[15] and loratadine-montelukast therapy[16] were found to be significantly more effective than both phenylephrine and placebo.

The Food and Drug Administration has stood by its 1976 approval of phenylephrine for nasal congestion as the debate continues.[8]

References[edit]

  1. ^ a b http://www.drugbank.ca/drugs/DB00388#identification
  2. ^ NZ Medicines and Medical Devices Safety Authority recommendation on phenylephrine (November 2004)
  3. ^ http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=72348406-e74f-46c5-b93d-34d07cffe1fd
  4. ^ http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=72348406-e74f-46c5-b93d-34d07cffe1fd
  5. ^ http://www.webmd.com/drugs/drug-76444-phenylephrine+HCl+Rect.aspx?drugid=76444&drugname=phenylephrine+HCl+Rect
  6. ^ Cooper, B. E. (2008). Review and Update on Inotropes and Vasopressors. AACN Advanced Critical Care, 19, 5–15.
  7. ^ Shen, Howard (2008). Illustrated Pharmacology Memory Cards: PharMnemonics. Minireview. p. 3. ISBN 1-59541-101-1. 
  8. ^ a b Hilenmeyer, K. (30 January 2007). "All stuffed up". Southwest Florida Herald-Tribune. 
  9. ^ Heldeles, L. and Hatton, R. (2006). "Oral phenylephrine: An ineffective replacement for pseudoephedrine?". Journal of Allergy and Clinical Immunology 118 (1): 279–280. doi:10.1016/j.jaci.2006.03.002. PMID 16815167. 
  10. ^ University of Florida (2006-07-19). "UF researchers question effectiveness of decongestant". Retrieved 2008-03-15. 
  11. ^ Eccles R (May 2006). "Phenylephrine an ineffective replacement for pseudoephedrine in response to the methamphetamine problem in the USA". BMJ. 
    Rapid Response to
    Tanne JH (February 2006). "Methamphetamine epidemic hits middle America". BMJ 332 (7538): 382. doi:10.1136/bmj.332.7538.382-b. PMC 1370997. PMID 16484253. 
  12. ^ Eccles, R. (2007). "Substitution of phenylephrine for pseudoephedrine as a nasal decongeststant. An illogical way to control methamphetamine abuse". British Journal of Clinical Pharmacology 63 (1): 10–14. doi:10.1111/j.1365-2125.2006.02833.x. PMC 2000711. PMID 17116124.  (January 2007)
  13. ^ Hatton, R.C. et al. (2007). "Efficacy and Safety of Oral Phenylephrine: A Systematic Review and Meta-Analysis" (abstract). Annals of Pharmacotherapy 41 (3): 381–390. doi:10.1345/aph.1H679. PMID 17264159. (published online Jan 2007)
  14. ^ Kollar, C.; Schneider, H.; Waksman, J.; Krusinska, E. (2007). "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". Clinical Therapeutics 29 (6): 1057–1070. doi:10.1016/j.clinthera.2007.05.021. PMID 17692721.  edit[unreliable medical source?]
  15. ^ a b Horak, F.; Zieglmayer, P.; Zieglmayer, R. �; Lemell, P.; Yao, R.; Staudinger, H.; Danzig, M. (2009). "A placebo-controlled study of the nasal decongestant effect of phenylephrine and pseudoephedrine in the Vienna Challenge Chamber". Annals of Allergy, Asthma & Immunology 102 (2): 116–20. doi:10.1016/S1081-1206(10)60240-2. PMID 19230461.  edit
  16. ^ a b Day, J. H.; Briscoe, M. P.; Ratz, J. D.; Danzig, M.; Yao, R. (2009). "Efficacy of loratadine-montelukast on nasal congestion in patients with seasonal allergic rhinitis in an environmental exposure unit". Annals of Allergy, Asthma & Immunology 102 (4): 328. doi:10.1016/S1081-1206(10)60339-0.  edit

External links[edit]