Tetryzoline

Absorption

When consumed orally, tetryzoline is rapidly absorbed from the gastrointestinal tract and can cross the blood-brain barrier. Following ocular administration of 0.05% tetryzoline, Cmax ranged from 0.068 to 0.380 ng/mL.

Toxicity

The Lowest published toxic dose (TDLo) of tetryzoline in children following oral administration is 175 mg/kg. Oral LD50 is 785 mg/kg in rats and 345 mg/kg in mice. Intraperitoneal LD50 is 122 mg/kg in rats and 110 mg/kg in mice. Subcutaneous LD50 is 500 mg/kg in rats.
Overdose following accidental oral ingestion in children may lead to profound sedation, possibly accompanied by profuse sweating, hypotension, and shock. In adults, hypertension, bradycardia, drowsiness, and rebound hypotension may be observed, in addition to a shock-like syndrome with hypotension and bradycardia. In one case, cardiovascular effects persisted for 36 hours after unintentional ingestion of tetrahydrozoline. Profound sedation has occurred in adults following accidental oral ingestion due to poisoning.
Overdose should be managed with supportive treatment, with the patient kept warm. Fluid maintenance therapy may be initiated if necessary. The respiratory rate dropping to 10 or below should be responded with oxygen therapy and respiratory assistance. Blood pressure should be carefully monitored to prevent a hypotensive crisis. There is no known antidote to tetryzoline overdose; however, one case report illustrates the successful use of naloxone in reversing the clinical signs and symptoms of tetryzoline overdose in a child. Naloxone has been used to revere clonidine overdose. The exact mechanism of action of naloxone as an antidote is not fully understood; however, it is understood that clonidine and tetryzoline work to inhibit central sympathetic outflow by activating alpha-2 adrenoceptors and inducing endogenous opiate release, which naloxone works to antagonize.

Originator

Tyzine,Pfizer,US,1954

The Uses of Tetryzoline

Tetrahydrozoline is generally used in the form of eye drops for constriction of blood vessels as well as locally for minor inflammations and bites.

Background

Tetryzoline, also known as tetrahydrozoline, is a derivative of imidazoline with central and peripheral alpha (α)-adrenergic properties. Available since the 1950s, tetryzoline is a selective α1-receptor agonist that is used as an ocular and nasal decongestant. Tetryzoline is found in a wide array of over-the-counter eye drops, including the most common brand, Visine. Tetryzoline is also found in combination products with other lubricants and anti-irritants, such as povidone, polyethylene glycol 400, dextran, and zinc sulfate. It is also used in combination with other drug classes, such as antihistamines, corticosteroids, and glucocorticoids in other countries. Tetryzoline is also found in nasal spray under the trade name Tyzine, which is used for decongestion of nasal and nasopharyngeal mucosa.
As it causes profound sedation in children and adults, tetryzoline is increasingly becoming scrutinized for possible drug overdose and toxicity from accidental ingestion. It has also been misused for non-therapeutic purposes as a causative drug for several cases of drug-facilitated sexual assault.

Indications

Tetryzoline is indicated for the temporary relief of discomfort and redness of the eye due to minor eye irritations as monotherapy or in combination with other eye lubricants and anti-irritants.
Tetryzoline is also indicated for decongestion of nasal and nasopharyngeal mucosa.

Definition

ChEBI: Tetryzoline is a member of imidazolines and a carboxamidine. It has a role as a sympathomimetic agent and a nasal decongestant. It is a conjugate base of a tetryzoline(1+).

Manufacturing Process

A mixture of 540 grams (9.0 mols) of ethylenediamine, 270 grams (1.53 mols) of 1,2,3,4tetrahydro-α-naphthoic acid, and 360 ml (4.32 mols) of concentrated hydrochloric acid was introduced into a two-liter, three-necked flask fitted with a thermometer, stirrer, and distillation takeoff. The mixture was distilled under a pressure of about 20 mm of mercury absolute until the temperature rose to 210°C. Thereafter, heating was continued under atmospheric pressure and when the temperature reached about 260°C, an exothermic reaction was initiated. The heat was then adjusted to maintain a reaction temperature of 275° to 280°C for 45 minutes and the mixture thereafter cooled to room temperature.
900 ml of 4 N hydrochloric acid was added and the aqueous layer stirred with warming until a clear, brown solution resulted. This brown solution was made strongly alkaline with sodium hydroxide. The oil that separated solidified and was collected on a filter leaving filtrate A. The solid was dissolved in 370 ml of alcohol with warming, and the solution was treated with 130 ml of concentrated hydrochloric acid with stirring and cooling. This acidified mixture was diluted with 300 ml of ether and chilled. The solid salt was collected and dried and the filtrate concentrated to approximately 300 ml, diluted with 300 ml of ether and the salt which separated collected and dried.
Filtrate A was extracted with ether, dried, acidified with alcoholic hydrogen chloride, and the salt which separated was collected and dried. There was thus obtained, when all the salt had been combined, 250 grams (69.3% of the theoretical yield) of 2-(1,2,3,4-tetrahydro-1-naphthyl)imidazoline hydrochloride, melting at 256° to 257°C.

Therapeutic Function

Nasal decongestant, Pharmaceutic aid

Pharmacokinetics

Tetryzoline is a sympathomimetic amine and an alpha-adrenergic agonist with vasoconstricting and decongestant properties. It works by constricting the smaller arterioles of the nasal passages and conjunctival blood vessels to ameliorate allergic rhinitis, nasal congestion, and ocular irritation. Tetryzoline is known to cross the blood-brain barrier to work on alpha-2 adrenoceptors and imidazole receptors, causing effects like hypotension, bradycardia, analgesia, hypothermia, sedation, and hypnosis.

Synthesis

Tetrahydrozoline, 2-(1,2,3,4-tetrahydro-1-naphthalenyl)-2-imidazoline (11.1.41), is synthesized in one step by the heterocyclization of 1-cyanotetraline with ethylenediamine [45].

Metabolism

No information is available.