Naphazoline Explained

Naphazoline is a medicine used as a decongestant, and a vasoconstrictor added to eye drops to relieve red eye. It has a rapid action in reducing swelling when applied to mucous membranes. It is a sympathomimetic agent with marked alpha adrenergic activity that acts on alpha-receptors in the arterioles of the conjunctiva to produce constriction, resulting in decreased congestion.

It was patented in 1934 and came into medical use in 1942.^[1]

Medical uses

Nasal administration

Nasal decongestant.

Ophthalmic drug administration

Eye drops (brand names Clear Eyes, and Cleari) narrowing swollen blood vessels (ophthalmic arteries, and ophthalmic veins) to relieve red eye.

Temporary red eye can safely be treated when the cause of the redness is established (e.g. cannabis induced corneal vasodilation).^[2] However, continuous use is not recommended without knowing an underlying condition.

Side effects

A few warnings and contraindications that apply to all naphazoline-containing substances intended for medicinal use are:

• Hypersensitivity to naphazoline
• Use in infants and children can result in central nervous system depression, leading to coma and marked reduction in body temperature
• Should be used with caution in patients with severe cardiovascular disease including cardiac arrhythmia and in patients with diabetes, especially those with a tendency toward diabetic ketoacidosis
• A possible association with stroke has been suggested.^[3]

Nasal administration

• Extended use may cause rhinitis medicamentosa, a condition of rebound nasal congestion.

Ophthalmic drug administration

Known side-effect:^{[4] [5]}

• Stinging
• Discomfort
• Irritation
• Increased red eyes
• Blurred vision
• Mydriasis
• Punctate keratitis
• Lacrimation (tears)
• Increased intraocular pressure

Contraindications

• Patients taking MAO inhibitors can experience a severe hypertensive crisis if given a sympathomimetic drug such as naphazoline HCl
• Drug interactions can occur with anaesthetics that sensitize the myocardium to sympathomimetics (e.g. cyclopropane or halothane cautiously)
• Exercise caution when applying prior to use of phenylephrine.

Pharmacology

Naphazoline is a mixed α₁- and α₂-adrenergic receptor agonist.^[6]

Chemistry

The non-hydrochloride form of Naphazoline has the molecular formula C₁₄H₁₄N₂ and a molar mass of 210.28 g/mol. The HCl salt form has a molar mass of 246.73 g/mol.

Society and culture

It is an active ingredient in several over-the-counter eye drop formulations including Clear Eyes, Rohto, Eucool, and Naphcon-A.^[7]

Illicit use

The nasal or ophthalmic form of naphazoline has been abused by heroin or cocaine drug addicts.^{[8] [9]} It's used as CNS stimulant and vasoconstrictor to enhance primary drug effects.

Notes and References

1. Book: Fischer J, Ganellin CR . Analogue-based Drug Discovery . 2006 . John Wiley & Sons . 9783527607495 . 552 . en.
2. Yazulla S . Endocannabinoids in the retina: from marijuana to neuroprotection . Progress in Retinal and Eye Research . 27 . 5 . 501–526 . September 2008 . 18725316 . 2584875 . 10.1016/j.preteyeres.2008.07.002 .
3. Zavala JA, Pereira ER, Zétola VH, Teive HA, Nóvak EM, Werneck LC . Hemorrhagic stroke after naphazoline exposition: case report . Arquivos de Neuro-Psiquiatria . 62 . 3B . 889–891 . September 2004 . 15476091 . 10.1590/S0004-282X2004000500030 . free .
4. Web site: Naphazoline - FDA prescribing information, side effects and uses . Drugs.com . en.
5. Web site: naphazoline ophthalmic (eye): Uses, Side Effects, Interactions, Pictures, Warnings & Dosing - WebMD . www.webmd.com . en.
6. Hosten LO, Snyder C . Over-the-Counter Ocular Decongestants in the United States - Mechanisms of Action and Clinical Utility for Management of Ocular Redness . Clinical Optometry . 12 . 95–105 . 2020 . 32801982 . 7399465 . 10.2147/OPTO.S259398 . free .
7. Encyclopedia: Green SM . 2008 . Ophthalmology: Naphazoline . Tarascon Pocket Pharmacopoeia 2009 . Jones and Bartlett . 978-0-7637-6572-9 .
8. van Montfrans GA, van Steenwijk RP, Vyth A, Borst C . Intravenous naphazoline intoxication . Acta Medica Scandinavica . 209 . 5 . 429–430 . 1981 . 7246278 . 10.1111/j.0954-6820.1981.tb11622.x .
9. 2020-08-01 . Naphazoline abuse . Reactions Weekly . en . 1815 . 1 . 251 . 10.1007/s40278-020-81577-1 . 195174995 . 1179-2051.