Phenylephrine

Namali Corea Unilever, Bedford, United Kingdom

ã 2007 Elsevier Inc. All rights reserved.

Introduction

Phenylephrine is a synthetic, sympathomimetic agent with predominantly alpha adreno-

ceptor stimulant activity. It has vasoconstrictor, decongestant, and weak bronchodilator
activity. Apart from ophthalmologic use, it is often given in combination with other drugs.
It may also have a more minor action to release norepinephrine from sympathetic nerve
endings. Phenylephrine was approved for use by the FDA in 1938.

Nomenclature
Name of the Clinical Phenylephrine hydrochloride
Form
Related Names Phenylephrine; adrianol; alconefrin; almefrin; biomidrin;
Source: EMTREE biomydrin; derizene; disneumon pernasal; dristan nasal mist;
fenylephrine; idrianol; isonefrine; isophrine; isopto frin;
isoptofrin; levo phenylephrine; lexatol; l meta synephrine; l
phenylefrine; l phenylephrine; mesaton; metaoxedrine;
metaoxedrine chloride; meta sympathol; meta synephrine;
metasynephrine; mezaton; m synephrine; mydfrin;
neooxedrine; neophryn; neosynephrin; neo synephrine;
neosynephrine; neosynephrine hydrochloride; neo
synephrine thenfadil; neosynesin; neosynesine; "nostril"; n
105 to; phenylefrine; phenylephedrine; phenylephedrine
hydrochloride; phenylephrine bromide; 1 phenylephrine
hydrochloride; phenylephrine hydrochloride; prefrin; prefrin
liquifilm; rhinall 10; sucraphen; visadron; ’nostril’; 1 (3
hydroxyphenyl) 2 methylaminoethanol; 1 (meta
hydroxyphenyl) 2 methylaminoethanol; 3 hydroxy alpha
[(methylamino)methyl]benzyl alcohol; slv 325; slv325
Chemical Names 3 hydroxy alpha [(methylamino)methyl]benzyl alcohol; 1
(3hydroxyphenyl) 2 methylaminoethanol; 1 (meta
hydroxyphenyl) 2methylaminoethanol
CAS Number 59-42-7

1
2 Phenylephrine

Basic Chemistry
Chemical Structure
Structure

Comments The hydrochloride is an odorless, bitter-tasting, white

crystalline powder.
Chemical Formula C9 H13 N O2
Properties
Physical Properties Melting point is 140–145 C and 169–172 C for hydrochloride
and free base, respectively.
Molecular Weight 167.207
Solubility For hydrochloride:In ethanol 1 in 4, in water 1 in 2.
Ionization Constant
Value Salt Conditions Reference Comments
pka 8.9 -OH Dollery (1999)
pka 10.1 -NH- Dollery (1999)

Human Pharmacokinetics

Absorption is variable after oral administration and the compound undergoes 60% first-
pass metabolism.

Pharmacokinetic Properties

Prep. and Route

Value Units of Admin. Reference Comments

Absorption
Bioavailability 40 % oral Dollery (1999) Peak plasma
administration concentration
1-2 hours
Distribution
Volume of Distribution 200- l
500
Plasma Protein Binding
Metabolism Extensive metabolism occurs in the gut wall and liver. Phenylephrine
undergoes mainly sulfation and oxidative deamination, with less than
20% excreted unchanged. Both the parent compound and metabolites
are eliminated via the urine.
Plasma Half-Life 2-3 hrs
Bio Half-Life
Clearance
Routes of Elimination
 Phenylephrine 3

Targets-Pharmacodynamics

Phenylephrine is a relatively selective agonist for the alpha-1 adrenoceptors.

Target Name(s):
Alpha-1 adrenoceptors

Therapeutics

Phenylephrine is indicated for topical vasoconstrictor effects, mydriatic action, and acute
hypotension and is available for use by oral, topical, and parenteral administration. It is
available to the general public without prescription in numerous cold and flu preparations
for oral administration, usually in combination with paracetamol, caffeine, and other
agents. It can be used in preparations of local anesthetics to produce vasoconstriction to
localize regional and spinal anesthesia.
Although indicated for some patients with wide angle glaucoma (because it may
reduce production of aqueous humor), it is contraindicated in narrow angle glaucoma
because it may reduce fluid drainage through the Canal of Schlemm.

Indications

Prep. and Route

Value Units of Admin. Reference Comments

Mydriasis
Dosage up to 10 % solution as eye British Lower concentrations
drops National may be used to avoid
Formulary cardiac events.
(2003)
Nasal congestion
Dosage 0.25-0.5 % drops or spray Sweetman Administer to each nostril
et al (2002) every 4 hours as
required.
Nasal congestion
Dosage 5-20 mg oral Sweetman To be taken 3 or 4 times
et al (2002) daily.
Acute Hypotension
Dosage 2-5 mg subcutaneous or British Followed, if necessary, by
intramuscular National further doses of 1-10
injection Formulary mg.
(2003)
Acute Hypotension
Dosage 100-500 mg slow i.v. injection British Repeated as necessary
of a 1 mg/ml National after at least 15 minutes.
solution Formulary
(2003)
Acute Hypotension
Dosage 180 mg/min i.v. infusion British Reduced to 30-60 mg/min
National according to response.
Formulary
(2003)
4 Phenylephrine

Contraindications
Mydriasis: Narrow angle glaucoma, concurrent administration of MAOI’s; Acute Hypo-
tension: hypertension, pregnancy, severe hyperthyroidism; nasal congestion; heart failure;
angina; arrhythmias; myocardial infarction; pregnancy. Care in the elderly and very young
who are more susceptible.

Adverse Effects
Few adverse effects are seen when correct dose are used by local administration. Mydria-
sis: eye pain and stinging, blurred vision, photophobia, arrhythmias, hypertension, coro-
nary artery spasm; Acute Hypotension: hypertension, headache, bradycardia, arrhythmias,
peripheral ischemia, tachycardia, reflex bradycardia; rebound nasal congestion: local
irritation, rebound congestion, and chronic rhinitis after excessive use; peripheral vaso-
constriction; tissue necrosis on extravasation; anxiety and hallucinations

Agent-Agent Interactions

Agent Name Mode of Interaction

Many antihypertensive drugs Antagonism of hypotensive effect

MAOIs Possibly hypertensive crisis
Moclobemide Possibly hypertensive crisis
Antipsychotics Antagonism of pressor action
Doxapram Risk of hypertension
Ergotamine Increased risk of ergotism
Oxytocin Hypertension due to enhanced vasopressor effect of
vasoconstrictor sympathomimetics
Sympathomimnetics and Exacerbation of hypertensive and other sympathomimetic effects
cocaine
Ergot alkaloids Exacerbation of hypertensive and other sympathomimetic effects
Atropine like drugs Exacerbation of hypertensive effect

Pre-Clinical Research

Phenylephrine inhibits [3H]prazosin binding in rat brain cortex in a biphasic manner

(nH = 0.4) with Ki values of 0.24 and 9.7 mMMorrow and Creese (1986).

Pharmacokinetics
Potency

Prep. and Cell Exp.

Organ/ Route of Line/ End
Value Units Tissue Admin. Type Effects Point Reference Comments

Rat
DOSE MSDS: For phenylephrine
www.sigmaaldrich. hydrochloride
com
LD50 350 mg/kg p.o.
LD50 17 mg/kg i.p.
LD50 27 mg/kg s.c.
LD50 440 mg/kg i.v.
 Phenylephrine 5

Mouse
DOSE MSDS: www.sigmaaldrich. For phenylephrine
com hydrochloride
LD50 120 mg/kg p.o.
LD50 89 mg/kg i.p.
LD50 22 mg/kg s.c.
LD50 1120 mg/kg i.v.
Rabbit
DOSE MSDS: www.sigmaaldrich. For phenylephrine
com hydrochloride
LD50 22 mg/kg s.c.
LD50 500 g/kg i.v.
LD50 7200 mg/kg i.m.

Other Information – Web Sites

G Protein-Coupled Database (GPCRDB) gives extensive binding data on phenylephrine

in the Seeman database.
The PDSP Ki database lists 3 Ki values for ()-phenylephrine, 2 for (-)-phenylephrine,
and 3 for (+)-phenylephrine.
Phenylephrine is available from Sigma-Aldrich, product number P6126.
Toxnet: http://toxnet.nlm.nih.gov
British National Formulary: http://www.bnf.org

Journal Citations

Morrow, A.L., Creese, I., 1986. Characterization of alpha-1 adrenergic receptor subtypes in rat brain:
A reevaluation of [3H]WB 4101 and [3H]prazosin binding. Mol.Pharmacol., 29, 321–330.

Book Citations

Dollery, C., 1999. Dollery, C. (Ed.), Therapeutic Drugs, Edition 2. Churchill Livingstone, Edinburgh.
British National Formulary, 2003. British National Formulary, Edition 46. British Medical Association,
London.
Sweetman, S. C. et al., 2002. Sweetman, S.C., Blake, P.S., McGlashan, J.M., Parsons, A.V. (Ed.),
Martindale-The Complete Drug Reference, Edition 33. Pharmaceutical Press, UK.

Further Reading

Moreno-Ancillo and colleagues describe adverse effects of phenyepherine when used as eye drops:
Moreno-Ancillo, A., Munoz-Robles, M.L., Cabanas, R., Barranco, P. and Lopez-Serrano, M.C., Allergic
contact reactions due to phenylephrine hydrochloride in eyedrops, Ann. Allergy Asthma Immunol., 78(6)
(1997) 569–572