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Brymonidyna na twarz - Tajemnicze Piękno Naturalnej Pielęgnacji
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].
Pharmacology
Brinzolamide, either as a standalone agent or in combination with brimonidine, is approved by the FDA for the treatment of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma. 8,5 Brinzolamide is also approved in Europe to be used in combination with timolol to treat the same conditions. 7
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Avoid life-threatening adverse drug events with our Clinical APIInhibition of carbonic anhydrase II (CA-II) in the ciliary process of the eye slows the formation of bicarbonate and thus fluid flow, lowering intraocular pressure (IOP). 3,4
The IOP-reducing effect of brinzolamide as adjunctive therapy to the prostaglandin analog travoprost was studied. Following a 4-week run-in with travoprost, patients with an IOP ≥19 mmHg were randomized to receive added treatment with brinzolamide or timolol. An additional decrease in mean diurnal IOP of 3.2 to 3.4 mmHg for the brinzolamide group and 3.2 to 4.2 mmHg for the timolol group were observed. There was an overall higher incidence of non-serious ocular adverse reactions, mainly related to signs of local irritation, in the brinzolamide/travoprost groups. The events were mild and did not affect the overall discontinuation rates in the studies. 11
A clinical trial was conducted with brinzolamide in 32 pediatric patients less than 6 years of age, diagnosed with glaucoma or ocular hypertension. Some patients were naive to IOP therapy whilst others were on other IOP-lowering medicinal product(s). Those who had been on previous IOP medicinal products were not required to discontinue their IOP medicinal product(s) until the initiation of monotherapy with brinzolamide. 11
Associated Data
The data presented in this study are available in article and Supplementary Materials.
Brimonidine, a selective alpha-2 adrenergic agonist used for the treatment of open-angle glaucoma, has been shown to cause neurological side effects such as unresponsiveness, lethargy, hypoventilation, and stupor, mimicking opioid toxicity. We report one case of transient encephalopathy in a toddler, in whom accidental brimonidine toxicity was suspected and then confirmed by a toxicology study. The healthy 8-month-old girl was taken to the pediatric ER since she was drowsy and hypotonic with miosis. The computed tomography scan of her brain and toxicological workup of her blood and urine were negative. Starting from the fourth hour, the child progressively improved, and by the sixth hour, she recovered to a normal state of consciousness. A survey of available drugs within the child’s reach showed the presence of brimonidine. Thus, ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) was applied to quantify the brimonidine in urine and plasma samples, showing levels of 8.40 ng/mL and 0.79 ng/mL, respectively. To our knowledge, this is the first report to determine brimonidine levels in urine and plasma using UPLC-MS/MS. Insufficient knowledge on the part of family members about the potential hazards of an apparently innocuous, topical medication such as eye drops may put children at a greater risk of poisoning. Necessary warnings should be given to parents with greater care when prescribing this medication.
Keywords: brimonidine, eye drop poisoning, tandem mass spectrometryReferences
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