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Brymonidyna na twarz - Tajemnicze Piękno Naturalnej Pielęgnacji
RESULTS
Representative pictures of a mouse from each group. (A) Group 1: 1% brimonidine cream before UVR. (B) Group 2: 0.33% brimonidine gel before UVR. C) Group 3: 1% brimonidine cream after UVR. (D) Group 4: UVR, no drug treatment (UVR control). (E) Group 5: 1% brimonidine cream without UVR. (F) The mice from Group 1 and 5 developed erythema after the application of 1% brimonidine cream.
(a) Representative SCC on the back of a UVR control mouse. (b) Overview histology picture (H&E staining) (c). Close up of SCC keratin pearls.
Kaplan–Meier plot showing the probability of survival without a tumor of at least 1 mm in diameter for the groups treated with 1% brimonidine cream before UVR (Group 1), 0.33% brimonidine gel before UVR (Group 2), 1% brimonidine cream after UVR (Group 3) and UVR alone (Group 4). No tumors developed in the nonirradiated Group 5. Panels: (a) first tumor, (b) second tumor, and (c) third tumor.
Case Presentation
At a physical examination, the child was drowsy and rousable for brief moments with persistent crying, hypotonia, and bilateral miosis. Upon palpation of the skull, no swellings or bony steps were observed. The child had pinkish, pale skin, a pernicious, diffusely harsh vesicular murmur in the chest with good air penetration, and strong and rhythmic cardiac activity. Her abdomen was treatable. She was afebrile, with an SpO2 of 99% in room air, an ABP of 99/51 mmHg, and a heart rate of 113/min.
In an attempt to identify a possible toxic agent, the parents were asked to check the home environment within the child’s reach. Later on, the mother reported that the vials of brimonidine-based eye drops used by the grandfather were found empty on the sofa near where the little girl had been playing.
Discussion
In 2021, Ghaffari et al. reported a series of six cases found in the literature on the systemic side effects of the accidental oral or nasal ingestion of brimonidine eye drops in children, reported up to the end of 2019 [31], together with five additional new cases from personal observation. Their ages ranged between 9 days and 4 years.
Miosis may be a helpful sign when investigating brimonidine intoxication but should not be considered a must for confirming the diagnosis.
The duration of hypotonia may be variable. Ghaffari et al. report that in all of their cases, hypotonia lasted about twice the time needed for recovery to a normal level of consciousness [31].
At the most recent follow-up visit, 11 months after the reported event, the child was doing fine, her parents reported a series of typical age-related behaviors, and we found no evidence of a residual defect or alteration upon careful physical examination.
The brimonidine concentration in the plasma sample collected from our patient about ten hours after its accidental ingestion was 0.790 ng/mL. Thus, in our 8-month-old girl, plasma concentrations were about 13-fold higher than the maximum mean plasma concentration observed in adults. Of course, it has to be remarked that this is oral versus topical consumption.
This level was similar to that found in an infant with Peters anomaly being treated with ophthalmic drops containing 0.2% brimonidine. The young patient was brought to the emergency department, proving lethargic, hypotonic, hypothermic, and unresponsive to stimulation. These episodes were repeated five times during the hospitalization period. In this case, brimonidine concentrations were reported to be 1.459 ng/mL and 0.700 ng/mL in the plasma 0–3 and 6 h after instillation, respectively [19]. These elevated plasma levels, along with the resolution of symptoms following brimonidine withdrawal, indicated the drug as the possible cause of the reported intermittent coma episodes [19].
Introduction
Brimonidine is a selective alpha-2 adrenergic agonist, with a 1780-fold selectivity for α2- vs. α1-adrenergic receptors [1], and is increasingly used for the treatment of open-angle glaucoma (OAG) in children and adults [2]. After cataracts, glaucoma is the second leading cause of blindness in the world [3]. Open-angle glaucoma is the most common type of glaucoma among White and Black populations [3,4]. The estimated number of people with open-angle glaucoma in 2015 was 57.5 million, and this number was projected to increase to 65.5 million by 2020 [5]. The incidence of open-angle glaucoma increases with age, particularly in White and Black patients [6,7,8]. The prevalence of open-angle glaucoma is
Brimonidine is reported to be up to 12-fold more alpha-2-selective than clonidine and up to 32-fold more alpha-2-selective than apraclonidine (p-aminoclonidine) [10].
Brimonidine lowers intraocular pressure through a dual mechanism. It inhibits adenylyl cyclase with a decrease in cyclic adenosine monophosphate (AMP) levels and noradrenaline release through alpha-2 receptor activation, thus reducing aqueous humor production [11] and stimulating the outflow of aqueous humor via the uveoscleral pathway [12]. This latter mechanism is responsible for the drug effect following chronic treatment [13]. Although more polar and less lipophilic than clonidine ( Figure 1 ), brimonidine is known to cross the blood–brain barrier [14].
There are only limited data on the safety of brimonidine for children. The initial clinical trials mainly involved patients aged 2–7 years with a diagnosis of glaucoma, and no trials enrolled patients aged less than 1 year [10]. However, as it does not cause reduced pulmonary function and heart rate (HR), unlike β-adrenergic blocking agents, it is licensed for use in children over 5 years old [20]. Yet, a child’s lower weight could make the patient more susceptible to complications, thus, the pediatric age group is at greater risk [21,22]. In Italy, brimonidine administration to children aged 2 to 12 years is not recommended.
Brimonidine Eye Drops within the Reach of Children: A Possible Foe
3 Department of Innovative Technologies in Medicine and Dentistry, “Gabriele d’Annunzio” University of Chieti-Pescara, 66100 Chieti, Italy
Carmela Salladini
Patrizia Ballerini
3 Department of Innovative Technologies in Medicine and Dentistry, “Gabriele d’Annunzio” University of Chieti-Pescara, 66100 Chieti, Italy
Claudia Rossi
3 Department of Innovative Technologies in Medicine and Dentistry, “Gabriele d’Annunzio” University of Chieti-Pescara, 66100 Chieti, Italy
Maurizio Aricò
3 Department of Innovative Technologies in Medicine and Dentistry, “Gabriele d’Annunzio” University of Chieti-Pescara, 66100 Chieti, Italy
Received 2024 Jan 29, Revised 2024 Feb 26, Accepted 2024 Mar 5.Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).