同: Neo-Synephrine

WordNet

a complex consisting of an organic base in association with hydrogen chloride
a powerful vasoconstrictor used to dilate the pupils and relieve nasal congestion

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/08/07 10:21:16」(JST)

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Phenylephrine is a selective α₁-adrenergic receptor agonist of the phenethylamine class used primarily as a decongestant, as an agent to dilate the pupil, and to increase blood pressure. Phenylephrine is marketed as an alternative for the decongestant pseudoephedrine, though clinical studies show Phenylephrine to be no more effective than placebo.^[1]^[2] Phenylephrine can also cause a decrease in heart rate through reflex bradycardia.^[3]

Medical uses

Decongestant

Phenylephrine is used as a decongestant sold as an oral medicine or as a nasal spray. It is a common ingredient in over-the-counter decongestants. Other decongestants include oxymetazoline (Brand name: Afrin) and Pseudoephedrine (Brand name: Sudafed)

Oral phenylephrine is extensively metabolized by monoamine oxidase,^[4] an enzyme that is present on the outside of cells, throughout the body.^[5] Compared to intravenous pseudoephedrine, phenylephrine has a reduced and variable bioavailability; only up to 38%.^[4]^[6] 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 receptors which cause blood vessels to constrict. Phenylephrine may cause side effects such as headache, reflex bradycardia, excitability, restlessness and cardiac arrhythmias. Phenylephrine is not suggested for use in patients with hypertension.^[7]

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 multiple studies not being able to come to an agreement.^[1]^[2] 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.^[8]

Hemorrhoids

Hemorrhoids are caused by swollen veins in the rectal area.^[9] Phenylephrine can be used topically to prevent symptoms of hemorrhoids. Since phenylephrine is a vasoconstrictor, the blood vessels are narrowed, reducing the pain associated with hemorrhoids. Products for treatment may also include substances that will form a protective barrier over the inflamed area, resulting in less pain when feces is passed.^[10]

Mydriatic

Phenylephrine is used as an eye drop to dilate the pupil to facilitate visualization of the retina. It is often used in combination with tropicamide 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 anestheic is applied.^[11]

Vasopressor

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. The elimination half life of phenylephrine is about 2.5 to 3.0 hours.^[12] 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 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.^[13]

Phenylephrine hydrochloride at 0.25% is used as a vasoconstrictor in some suppository formulations.^[14]

Detumescent

Phenylephrine is used by urologists to abort priapism. It is diluted significantly 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 1 hour, another form of therapy is considered.^[15]

Side effects

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.^[16] Patients 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.^[17]

Phenylephrine is pregnancy category C. Due to the lack of studies done in animals and in humans, it is not known if there is harm to the fetus. Phenylephrine should only be given to pregnant women who have a clear need.^[17]

Because this medication is a sympathomimetic amine without beta-adrenergic activity, it does not increase contractility force and output of the cardiac muscle. It may increase blood pressure significantly to elicit a bradycardiac reflex through stimulation of vascular (likely carotid) baroreceptors (result: decrease heart rate).

A common side effect during IV administration is reflex bradycardia.^[18]

Extended use may cause rhinitis medicamentosa, a condition of rebound nasal congestion.^[8]

Drug 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 calcium channel blockers, ACE inhibitors and benzodiazepines. Patients taking these medications may need a higher dose of phenylephrine to achieve a comparable increase in blood pressure.^[19]

Substitute for pseudoephedrine

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.^[20] Phenylephrine has been off patent for some time, and many generic brands are available.

Questions about effectiveness

Pharmacists Leslie Hendeles and Randy Hatton of the University of Florida suggested in 2006 that oral phenylephrine is ineffective as a decongestant at the 10-mg dose used, arguing that the studies used for the regulatory approval of the drug in the United States in 1976 were inadequate to prove effectiveness at the 10-mg dose, and safety at higher doses.^[21]

A 2007 meta-analysis by Hatton et al concluded that the evidence for its effectiveness is insufficient,^[22] 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, though as with other studies finding this, GSK has many products containing Phenylephrine which has caused some speculation to selective publishing or other controversial techniques.^[23] In a 2007 study by Wyeth Consumer Healthcare notes that 7 studies available in 1976 support the efficacy of phenylephrine at a 10 mg dosage.^[24]

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. Pseudoephedrine and loratadine-montelukast therapy were found to be significantly more effective than both phenylephrine and placebo.^[1]^[2]

The Food and Drug Administration has stood by its 1976 approval of phenylephrine for nasal congestion as the debate continues.^[20]

References

^ ^a ^b ^c Horak, F.; Zieglmayer, P.; Zieglmayer, R.; Lemell, P.; Yao, R.; Staudinger, H.; Danzig, M. (11 November 2008). "A placebo-controlled study of the nasal decongestant effect of phenylephrine and pseudoephedrine in the Vienna Challenge Chamber". Annals of Allergy, Asthma & Immunology (February 2009) 102 (2): 116–20. doi:10.1016/S1081-1206(10)60240-2. PMID 19230461. edit
^ ^a ^b ^c 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
^ "UCSF drug learning module: Phenylephrine". UCSF. UCSF. Retrieved 5 February 2015.
^ ^a ^b "DrugBank: Phenylephrine (DB00388)". drugbank.ca. Retrieved 4 April 2015.
^ Shih JC, Chen K; Chen (August 2004). "Regulation of MAO-A and MAO-B gene expression". Curr. Med. Chem. 11 (15): 1995–2005. doi:10.2174/0929867043364757. PMID 15279563.
^ NZ Medicines and Medical Devices Safety Authority recommendation on phenylephrine (November 2004)
^ "DailyMed - PHENYLEPHRINE HYDROCHLORIDE- phenylephrine hydrochloride injection". nih.gov. Retrieved 4 April 2015.
^ ^a ^b "Neo-Synephrine Nasal Spray Drug Information, Professional". drugs.com. Retrieved 4 April 2015.
^ http://www.mayoclinic.org/diseases-conditions/hemorrhoids/basics/definition/con-20029852
^ "phenylephrine rectal". webmd.com. Retrieved 4 April 2015.
^ http://akorn.com/documents/catalog/sell_sheets/17478-205-10.pdf
^ Kanfer I, Dowse R, Vuma V (November 1993) “Pharmacokinetics of oral decongestants” Pharmacotherapy 13(6 pt 2) PMID 7507589
^ Cooper, B. E. (2008). Review and Update on Inotropes and Vasopressors. AACN Advanced Critical Care, 19, 5–15.
^ "DailyMed - PREPARATION H- cocoa butter and phenylephrine hydrochloride suppository". nih.gov. Retrieved 4 April 2015.
^ "Priapism : American Urological Association". auanet.org. Retrieved 4 April 2015.
^ Shen, Howard (2008). Illustrated Pharmacology Memory Cards: PharMnemonics. Minireview. p. 3. ISBN 1-59541-101-1.
^ ^a ^b http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203826s000lbl.pdf
^ "Medscape: Medscape Access". medscape.com. Retrieved 4 April 2015.
^ "Vazculep_FINAL_PI.pdf" (PDF). google.com. Retrieved 4 April 2015.
^ ^a ^b Hilenmeyer, K. (30 January 2007). "All stuffed up". Southwest Florida Herald-Tribune.
^ 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.
^ 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)
^ 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?]}
^ Desjardins, P.J. & Berlin, R.G. (2007). "Efficacy of phenylephrine". British Journal of Clinical Pharmacology 64 (4): 555–556. doi:10.1111/j.1365-2125.2007.02935.x.

External links

Drugs.com - Phenylephrine
MedlinePlus: Phenylephrine
U.S. National Library of Medicine: Drug Information Portal - Phenylephrine
Neosynephrine Intravenous DIlution Guidelines: [1]

UpToDate Contents

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1. Peripartum cardiomyopathy: Treatment and prognosis
2. フェニレフリンおよび類似構造のうっ血除去薬：小児の中毒 phenylephrine and related decongestants pediatric poisoning
3. 昇圧剤および強心剤の使用 use of vasopressors and inotropes
4. OTC咳止め・かぜ薬：小児の中毒へのアプローチ over the counter cough and cold preparations approach to pediatric poisoning
5. 持続勃起症 priapism

English Journal

Ultrasound-assisted (R)-phenylephrine whole-cell bioconversion by S. marcescens N10612.

Zang CZ1, Kan SC1, Yeh CW1, Lin CC1, Shieh CJ2, Liu YC3.
Ultrasonics sonochemistry.Ultrason Sonochem.2015 Sep;26:415-21. doi: 10.1016/j.ultsonch.2015.01.010. Epub 2015 Jan 30.
The strain Serratia marcescens N10612 is used to perform the bioconversion of 1-(3-hydroxyphenyl)-2-(methyamino)-ethanone (HPMAE) to (R)-phenylephrine ((R)-PE), which is an ephedrine drug substitute. The use of an ultrasound approach is found to improve the efficiency of the (R)-PE bioconversion. Th
PMID 25691009

Basal activity of voltage-gated Ca(2+) channels controls the IP3-mediated contraction by α1-adrenoceptor stimulation of mouse aorta segments.

Leloup AJ1, Van Hove CE2, De Meyer GR3, Schrijvers DM4, Fransen P5.
European journal of pharmacology.Eur J Pharmacol.2015 Aug 5;760:163-71. doi: 10.1016/j.ejphar.2015.04.011. Epub 2015 Apr 22.
α1-Adrenoceptor stimulation of mouse aorta causes intracellular Ca(2+) release from sarcoplasmic reticulum Ca(2+) stores via stimulation of inositoltriphosphate (IP3) receptors. It is hypothesized that this Ca(2+) release from the contractile and IP3-sensitive Ca(2+) store is under the continuous d
PMID 25913240

Early prediction of norepinephrine dependency and refractory septic shock with a multimodal approach of vascular failure.

Conrad M1, Perez P1, Thivilier C1, Levy B2.
Journal of critical care.J Crit Care.2015 Aug;30(4):739-43. doi: 10.1016/j.jcrc.2015.03.029. Epub 2015 Apr 8.
PURPOSE: The purpose of the study is to improve our ability to detect catecholamine dependency and refractory septic shock.METHODS: Fifty-one patients with septic shock were studied within the first 4 hours of norepinephrine administration. Patients were divided into 2 groups according to their evol
PMID 25900257

Japanese Journal

症例フェニレフリン塩酸塩によるアレルギー性接触眼瞼結膜炎の1例

松尾明子,林宏明,藤本亘
西日本皮膚科 73(3), 217-220, 2011-06
NAID 40018897219

Multivariate Optimization and Validation of a Capillary Electrophoresis Method for the Simultaneous Determination of Dextromethorphan Hydrobromur, Phenylephrine Hydrochloride, Paracetamol and Chlorpheniramine Maleate in a Pharmaceutical Preparation Using Response Surface Methodology

PALABIYIK I. Murat,ONUR Feyyaz
Analytical sciences : the international journal of the Japan Society for Analytical Chemistry 26(8), 853-859, 2010-08-10
NAID 10026784731

ラットのフェニレフリン誘発尿道内圧上昇に対するシロドシン(KMD-3213)の作用持続性(<特集>シロドシン)

小林護,立道聡,小林久美,今村卓広,丸山格,山崎芳伸,柴田信男
藥學雜誌 126(増刊号), 231-236, 2006-03-01
… The duration of action of Silodosin (KMD-3213) against the phenylephrine-induced increase in intraurethral pressure in urethane-anesthetized rats was compared with that of tamsulosin hydrochloride. … Phenylephrine, at a dose of 30μg/kg, was infused (infusion rate: 36ml/h; …
NAID 110006155000

「フェニレフリン」

Phenylephrine
Systematic (IUPAC) name
	(R)-3-[-1-hydroxy-2-(methylamino)ethyl]phenol
Clinical data
Pregnancy; category	US: C (Risk not ruled out);
Legal status	UK: General sales list (GSL, OTC); US: OTC;
Routes of; administration	Oral, intranasal, ophthalmic, intravenous, intramuscular
Pharmacokinetic data
Bioavailability	38% through GI tract
Protein binding	95%
Metabolism	Hepatic (monoamine oxidase)
Biological half-life	2.1–3.4 h
Identifiers
CAS Registry Number	59-42-7 ; 61-76-7 (hydrochloride)
ATC code	C01CA06 R01AA04, R01AB01 (combinations), R01BA03, S01FB01, S01GA05
PubChem	CID: 6041
IUPHAR/BPS	485
DrugBank	DB00388
ChemSpider	5818
UNII	1WS297W6MV
KEGG	D08365
ChEBI	CHEBI:8093
ChEMBL	CHEMBL1215
Chemical data
Formula	C9H13NO2
Molecular mass	167.205 g/mol
	SMILES O[C@H](c1cc(O)ccc1)CNC ;
	InChI 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 ; Key:SONNWYBIRXJNDC-VIFPVBQESA-N ;
(what is this?) (verify)

　　[★]

英: phenylephrine
ラ: phenylephrinum
化: 塩酸フェニレフリン phenylephrine hydrochloride
商: ネオシネジン。点眼液(オフミック、サンドール、ミドリン)

交感神経作動薬

α1受容体作動薬

severe AS, in nocardiac surgeryで低血圧に陥ったときに昇圧のために使うらしい。少なくとも米では。他の手術でも普通に昇圧目的で使われているのかもしれない。

「hydrochloride」

　　[★] 塩酸塩、ハイドロクロライド　

[danzig09-1] Horak, F.; Zieglmayer, P.; Zieglmayer, R.; Lemell, P.; Yao, R.; Staudinger, H.; Danzig, M. (11 November 2008). "A placebo-controlled study of the nasal decongestant effect of phenylephrine and pseudoephedrine in the Vienna Challenge Chamber". Annals of Allergy, Asthma & Immunology (February 2009) 102 (2): 116–20. doi:10.1016/S1081-1206(10)60240-2. PMID 19230461. edit

[yao09-2] 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

[3] "UCSF drug learning module: Phenylephrine". UCSF. UCSF. Retrieved 5 February 2015.

[DB-4] "DrugBank: Phenylephrine (DB00388)". drugbank.ca. Retrieved 4 April 2015.

[pmid15279563-5] Shih JC, Chen K; Chen (August 2004). "Regulation of MAO-A and MAO-B gene expression". Curr. Med. Chem. 11 (15): 1995–2005. doi:10.2174/0929867043364757. PMID 15279563.

[6] NZ Medicines and Medical Devices Safety Authority recommendation on phenylephrine (November 2004)

[dailymed.nlm.nih.gov-7] "DailyMed - PHENYLEPHRINE HYDROCHLORIDE- phenylephrine hydrochloride injection". nih.gov. Retrieved 4 April 2015.

[nasal-8] "Neo-Synephrine Nasal Spray Drug Information, Professional". drugs.com. Retrieved 4 April 2015.

[9] ttp://www.mayoclinic.org/diseases-conditions/hemorrhoids/basics/definition/con-20029852

[10] "phenylephrine rectal". webmd.com. Retrieved 4 April 2015.

[11] ttp://akorn.com/documents/catalog/sell_sheets/17478-205-10.pdf

[12] Kanfer I, Dowse R, Vuma V (November 1993) “Pharmacokinetics of oral decongestants” Pharmacotherapy 13(6 pt 2) PMID 7507589

[13] Cooper, B. E. (2008). Review and Update on Inotropes and Vasopressors. AACN Advanced Critical Care, 19, 5–15.

[14] "DailyMed - PREPARATION H- cocoa butter and phenylephrine hydrochloride suppository". nih.gov. Retrieved 4 April 2015.

[15] "Priapism : American Urological Association". auanet.org. Retrieved 4 April 2015.

[pharmnemonics-16] Shen, Howard (2008). Illustrated Pharmacology Memory Cards: PharMnemonics. Minireview. p. 3. ISBN 1-59541-101-1.

[accessdata.fda.gov-17] ttp://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203826s000lbl.pdf

[18] "Medscape: Medscape Access". medscape.com. Retrieved 4 April 2015.

[19] "Vazculep_FINAL_PI.pdf" (PDF). google.com. Retrieved 4 April 2015.

[HeraldTribune-20] Hilenmeyer, K. (30 January 2007). "All stuffed up". Southwest Florida Herald-Tribune.

[Hendeles2006-21] 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.

[Annals-22] 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)

[GSK-23] 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?]}

[Desjardins2007-24] Desjardins, P.J. & Berlin, R.G. (2007). "Efficacy of phenylephrine". British Journal of Clinical Pharmacology 64 (4): 555–556. doi:10.1111/j.1365-2125.2007.02935.x.

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案内

案内

phenylephrine hydrochloride