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Brymonidyna na twarz - Tajemnicze Piękno Naturalnej Pielęgnacji
Identification
Brinzolamide is a carbonic anhydrase inhibitor used for the reduction of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma.
Brinzolamide is a highly specific, non-competitive, reversible carbonic anhydrase II (CA-II) inhibitor indicated to reduce ocular pressure in patients with ocular hypertension or open-angle glaucoma. 5 Although the exact pathophysiology of glaucoma is still unknown, one of the main hallmarks of this disease is vascular dysregulation and abnormalities. 1,2 The resulting vascular resistance increases intraocular pressure, thus impairing ocular perfusion. 1,2 Although systemic anti-carbonic anhydrase (CA) therapy has been used for almost 50 years with varying degrees of success, systemic administration results in an increase in incidences of adverse effects. 1,2
Brinzolamide was developed as a topical solution to the systemic side effects and dorzolamide, the first-ever approved topical CA inhibitor with contrasting results and evidence. 2 Unlike dorzolamide, brinzolamide has a higher lipophilicity to facilitate diffusion across the blood-retinal barrier. 2 Brinzolamide was approved by the FDA in 1998 as a standalone product and in 2013 as a combination product with brimonidine tartrate. 5,6 In Europe, it was also approved as a combination product with timolol in 2008. 7
Type Small Molecule Groups Approved Structure
Structure for Brinzolamide (DB01194)
Weight Average: 383.507Monoisotopic: 383.064332867 Chemical Formula C12H21N3O5S3 Synonyms Poor quality drug data slowing you down?
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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].
Biochemical Study
A total of 100 μL of plasma/urine study samples, calibrators, and QCs were added to 300 μL of IS working solution (acetonitrile containing IS 2 ng/mL for plasma sample processing and 100 ng/mL for urine sample processing). After centrifugation, supernatants were transferred into other tubes and then evaporated until dry. The residues were reconstituted with 100 μL of mobile phase and finally transferred into vials for UPLC-MS/MS analysis. Altogether, 10 μL of the sample was injected into the ion source. More details on the calibrator and quality control materials, sample preparation, and UPLC-MS/MS analysis are fully reported in the Supplementary Materials.
The UPLC/MS/MS analysis performed on the urine sample revealed 8.40 ng/mL brimonidine concentration levels, supporting the initial clinical suspicion. The chromatograph in Figure 2 clearly highlights the presence of brimonidine in the patient’s urine sample.
Chromatographic separation of (A) brimonidine (quantifier), (B) brimonidine (qualifier), and (C) internal standard brimonidine-d4 in urine sample of the study child.
The clinical suspicion was further supported by the analysis of the patient’s plasma sample with brimonidine concentration levels of 0.79 ng/mL, as shown in the chromatograph reported in Figure 3 .
Chromatographic separation of (A) brimonidine (quantifier), (B) brimonidine (qualifier), and (C) internal standard brimonidine-d4 in plasma sample of the study child.