More than meets the eye: a scoping review on the non-medical uses of THZ eye drops

Abstract

Tetrahydrozoline is an alpha agonist imidazole derivative found in over-the-counter decongestive eye and nasal drops. The drug was patented in 1954 and was available for medical use in 1959. This drug recently gained the attention of law enforcement as it has been utilized in criminal activity such as homicide and drug-facilitated sexual assault. The aim of this scoping review is to scope the literature for all mentions of tetrahydrozoline eye/nasal drops use in a non-medical context to delineate areas of future research and development. We used Google Scholar and PUBMED/Medline databases to search for non-medicinal and criminal uses of THZ. The search word used was “tetrahydrozoline.” A total of 15 articles matched our criteria. Among the case reports, two (11.1%) cases reported on drug-facilitated sexual assault, and two (11.1%) cases used THZ eyedrops to attempt suicide. Incidental ingestion of THZ eyedrops was reported in eight (44.4%) cases, three (16.7%) cases of attempted murder were reported, two (11.1%) cases of intentional ingestion were reported, and one (5.5%) case was a combination of drug-facilitated sexual assault and attempted murder. The most common clinical presentation was unexplained and resistant bradycardia and hypotension. THZ eye drops can be used to produce false negative results on drug tests. This study recognizes that THZ can be used in non-medicinal and criminal uses. There is room for future research and development. More studies should be conducted to better understand the mechanism of action, therapeutic window, and toxicity levels among various age groups at different methods of intake and to find an effective treatment in case of overdose. Eyedrop and nasal decongestant bottles should be designed with child proofing to prevent incidental ingestion and should contain warning labels. A fast and alternative test to GC/MS can be developed to ease the diagnosis of THZ toxicity. Purchases of this medication may need to be monitored.

Ingestion of Fluids of the Ocular Surface Containing Eye Drops of Imidazole Derivatives—Alpha Adrenergic Receptor Agonists as Paragons

“…This may occur due to accidental ingestion (in the pediatric population) or intentionally (as overdoses in suicides or other drug abuse) [46][47][48]. In a recent review of tetrahydrozoline poisoning cases by Menshawey and Menshawey [35], their findings were the same. Though, unlike selective alpha-2 agonists (usually prescription medications) [22], tetrahydrozoline drops are easily accessible and do not call for pharmacists or police investigators.…”

“…In this regard, one German study assessed the absorption of other imidazolines in animals and adult humans and found the elimination (65% urine and 22% feces) was “finished” at 96 h post-ingestion of a 390 mcg dose [ 32 ]. The data in this review were collected separately for clonidine and tetrahydrozoline [ 33 , 34 , 35 ].…”

“… Time course of events relevant in cases of poisoning with low-bioavailable imidazole derivatives. -⧌ (a triangular-shaped mark) indicates the half-life of the xenobiotic in serum (3–7 h for clonidine and 6 h for tetrahydrozoline); □ (a rectangle-shaped mark) represents the last sample with a detectable amount of xenobiotic (by GC/MS) (72 h for clonidine and 24 h for tetrahydrozoline) [ 33 , 34 , 35 ]. Symptoms of clonidine poisoning typically occur in two phases.…”

“…So, this study aims to summarize literature reports on tetrahydrozoline and alpha-2 adrenergic receptor agonists (clonidine taken as a prototypical medication) as harmful drugs, even in the form of fluid of the OS tainted with eye drops containing imidazole derivatives with the activity of alpha-adrenergic receptor agonists. [33][34][35]. Symptoms of clonidine poisoning typically occur in two phases.…”

Novel Deliberately Sensitive and Selective Tetrahydrozoline Voltammetric Sensors Integrated with a Copper Oxide Nanoparticle/Zeolite Platform

“…Recently, THZ has gained legal attention due to its abuse for criminal and nefarious nonmedicinal purposes such as drug-facilitated sexual assault (DFSA) and homicide. − Studies have shown that THZ concentration values higher than the upper normal limit values (13–210 ng mL –1 in blood or 11–40 ng mL –1 in urine) advocated the nonmedicinal uses of the drug . THZ is not a routinely suspected drug that is commonly used in criminal activity, especially in standard drug analysis screens, since its characteristics make it go unnoticed.…”