Tetryzoline

Tetryzoline (INN),^[3] also known as tetrahydrozoline, is a drug used in some over-the-counter eye drops and nasal sprays. Tetryzoline was patented in 1954, and came into medical use in 1959.^[4]

Tetryzoline

Clinical data
ATC code	R01AA06 (WHO) S01GA02 (WHO)
Identifiers
IUPAC name (RS)-2-(1,2,3,4-tetrahydronaphthalen-1-yl)-4,5-dihydro-1H-imidazole
CAS Number	84-22-0
PubChem CID	5419
ChemSpider	5226 Y
UNII	S9U025Y077
KEGG	D08578 Y
ChEBI	CHEBI:28674 Y
ChEMBL	ChEMBL1266 Y
CompTox Dashboard (EPA)	DTXSID1047861
ECHA InfoCard	100.001.384
Chemical and physical data
Formula	C13H16N2
Molar mass	200.285 g·mol−1
3D model (JSmol)	Interactive image
Melting point	117–119 °C (243–246 °F) [1] 256–257 °C (493–495 °F) for HCl-salt[2]
Solubility in water	Very soluble in water and ethanol, slightly soluble in chloroform and insoluble in diethylether[2]
SMILES N\1=C(\NCC/1)C3c2ccccc2CCC3
InChI InChI=1S/C13H16N2/c1-2-6-11-10(4-1)5-3-7-12(11)13-14-8-9-15-13/h1-2,4,6,12H,3,5,7-9H2,(H,14,15) Y Key:BYJAVTDNIXVSPW-UHFFFAOYSA-N Y
NY (what is this?)  (verify)

Side effects

Tetryzoline eye drops may cause blurred vision, eye irritation and dilated pupils.^[5] Tetryzoline is not suitable for prolonged use as its vasoconstrictive effects within the eye eventually decrease or stop. If tolerance to the drug has developed, ceasing its use may cause a rebound effect and increase redness of the eyes — ⁠a vasodilatory effect.^[6]

Intranasal use of tetryzoline may cause transient burning, stinging, or dryness of the mucosa and sneezing. Prolonged intranasal use often causes opposite effects in the form of rebound congestion with effects such as chronic redness, swelling and rhinitis. Prolonged use thus may result in overuse of the drug.^[5]

In children, it might cause profound sedation.^[7]

Overdose

Overdose most often causes slow heart rate. Respiratory depression, low blood pressure, constricted pupils, hypothermia, brief episodes of high blood pressure,^[8] drowsiness, headaches and vomiting may also occur.^[9] In serious cases some of these effects may result in circulatory shock.^[5] Most often overdoses occur in children who have ingested the drug.^[8]

There is no antidote for tetryzoline or other similar imidazoline analogue poisoning, but the symptoms can be alleviated. With treatment, death is rare.^[10]

Pharmacology

Pharmacodynamics

Tetryzoline is an alpha agonist for the alpha-1 receptor.^[11] This action relieves the redness of the eye caused by minor ocular irritants. Moreover, to treat allergic conjunctivitis, tetryzoline can be combined in a solution with antazoline.^[12]

Pharmacokinetics

In a healthy person, the biological half-life of tetryzoline is approximately 6 hours, and it is excreted in urine, chemically unchanged, at least in part. In one study, 10 people were given two drops of 0.5 mg/mL of tetryzoline eye drops (0.025–0.05 mg) at 0 hrs, 4 hrs, 8 hrs, and 12 hrs. Within a 24-hour time window, since the last dose of tetryzoline, the blood serum concentration of tetryzoline in the test subjects was 0.068-0.380 ng/mL and the urine concentration was 13–210 ng/mL. Both the blood and the urine levels of tetryzoline reached their maximums approximately 9 hrs after the last dose. These fluid-concentration levels correspond to normal ocular use of tetryzoline; thus, greater concentrations of tetryzoline in the blood and the urine of the user can indicate misuse of the drug or of poisoning with the drug.^[10]

Chemistry

Chemically, tetryzoline is a derivative of imidazoline. It has two enantiomers.

Society and culture

Names

Tetryzoline is the International Nonproprietary Name (INN).^[3]

Urban legend

An urban legend suggests that tetryzoline can cause violent diarrhea if given orally, such as by putting a few drops of Visine in an unsuspecting person's beverage. However, the actual results of the prank may be worse, varying from severe nausea and vomiting to seizures or a coma. Larger doses can cause death. Diarrhea is not a side effect.^[13]

Criminal use

In late August 2018, a South Carolina woman was charged with murdering her husband by putting eye drops containing tetryzoline in his drinking water. An autopsy found a high concentration of tetryzoline in his body.^[14][15][16]

Tetryzoline has been used as a date rape drug in a number of cases due to its ability to cause dizziness and unconsciousness.^[9]

In 2018, a 62 year-old woman in Pewaukee, Wisconsin, died in an apparent overdose or suicide involving tetryzoline and other substances; in November 2023 her caregiver was convicted of first-degree murder, following the allegation that her death was caused by a water bottle laced with Visine.^[17][18]

In 2019, a North Carolina paramedic was accused of using tetryzoline eye drops to cause the death of his wife. The blood sample results showed about 30–40 times higher than the therapeutic level of tetryzoline.^[19][20]

References

1. US 2731471, Synerholm M, Jules LH, Sahyun M, "Imidazoline Derivatives", issued 17 January 1956, assigned to Sahyun Laboratories.
2. Budavari S, O'Neil M, Smith A, Heckelman P, Obenchain J (2000). The Merck Index (12th ed.). Whitehouse Station, NJ, United States: Chapman & Hall Electronic Publishing Division. p. 1453. ISBN 978-1-58488-129-2. OCLC 46987702.
3. "International Non-Proprietary Names for Pharmaceutical Preparations. Recommended International Non-Proprietary Names: List 3" (PDF). World Health Organization. p. 474. Archived (PDF) from the original on 2016-09-11. Retrieved 30 August 2016.
4. Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 552. ISBN 978-3-527-60749-5.
5. "Tetrahydrozoline". toxnet.nlm.nih.gov. Archived from the original on 2017-01-03. Retrieved 2018-09-05.
6. McLaurin E, Cavet ME, Gomes PJ, Ciolino JB (March 2018). "Brimonidine Ophthalmic Solution 0.025% for Reduction of Ocular Redness: A Randomized Clinical Trial". Optometry and Vision Science. 95 (3): 264–271. doi:10.1097/OPX.0000000000001182. PMC 5839712. PMID 29461408.
7. "Tetryzoline". go.drugbank.com. Retrieved 2022-09-15.
8. Al-Abri SA, Yang HS, Olson KR (December 2014). "Unintentional pediatric ophthalmic tetrahydrozoline ingestion: case files of the medical toxicology fellowship at the University of California, San Francisco". Journal of Medical Toxicology. 10 (4): 388–91. doi:10.1007/s13181-014-0400-9. PMC 4252297. PMID 24760708.
9. Stillwell ME, Saady JJ (September 2012). "Use of tetrahydrozoline for chemical submission". Forensic Science International. 221 (1–3): e12-6. doi:10.1016/j.forsciint.2012.04.004. PMID 22554870.
10. Carr ME, Engebretsen KM, Ho B, Anderson CP (November 2011). "Tetrahydrozoline (Visine®) concentrations in serum and urine during therapeutic ocular dosing: a necessary first step in determining an overdose". Clinical Toxicology. 49 (9): 810–4. doi:10.3109/15563650.2011.615064. PMID 21972870. S2CID 20238499.
11. "Tetryzoline". go.drugbank.com. Retrieved 2022-12-21.
12. Castillo M, Scott NW, Mustafa MZ, Mustafa MS, Azuara-Blanco A (June 2015). "Topical antihistamines and mast cell stabilisers for treating seasonal and perennial allergic conjunctivitis" (PDF). The Cochrane Database of Systematic Reviews. 2015 (6): CD009566. doi:10.1002/14651858.CD009566.pub2. hdl:2164/6048. PMC 10616535. PMID 26028608.
13. "Visine Prank: Mickey Red Eyes". Snopes. 29 June 2009. Retrieved 28 July 2010.
14. "US wife accused of 'fatally poisoning husband with eyedrops'". BBC. 4 September 2018. Retrieved 4 September 2018.
15. Police: Woman kills husband by putting eye drops in water, Associated Press, August 31, 2018
16. Connelly E (1 September 2018). "Wife admits fatally poisoning 'unfaithful' hubby with eye drops: cops" (Newspaper). New York Post. Archived from the original on 2018-09-02. Retrieved 3 September 2018.
17. Hutchinson B (8 June 2021). "Wisconsin woman arrested, accused of murdering friend with eye drops: An investigation alleges the victim's water bottle was laced with Visine". ABC News.
18. Deliso M (14 November 2023). "Wisconsin woman found guilty of killing friend with eye drops". ABC News.
19. Jacobo J, Stein B (23 December 2019). "Paramedic accused of fatally poisoning his wife with ingredient found in eye drops: Prosecutors". ABC News. Retrieved 2022-09-15.
20. Lee BY (18 January 2020). "How Visine Eye Drops In The Mouth Can Kill, Here Are Two Cases". Forbes. Retrieved 2022-09-15.