The use of antidotes for calcium gluconate extravasation: an experimental study in mice

[Abstract] Background: Calcium gluconate extravasation is a process that can cause serious lesions, such as necrosis and calcification of the soft tissues. The aim of the present study was to analyze the beneficial effects of four possible local antidotes for calcium gluconate extravasation: hyaluronidase, sodium thiosulfate, triamcinolone acetonide, and physiologic saline solution. Methods: Seventy-four BALB/c mice were used in the study. The substances selected for use in this study were calcium gluconate (4.6 mEq/ml), hyaluronidase (1500 IU/ml), sodium thiosulfate (25%), triamcinolone acetonide (40 mg/ml 0.5 mg/kg), and saline solution 0.9%. Five minutes were allowed to lapse after the calcium gluconate infiltration, and then an antidote was infiltrated. After 3 weeks, a skin biopsy was performed and a radiographic and histologic study was carried out. Results: Only in the group infiltrated with sodium thiosulfate did all skin lesions disappear after the 3-week period after infiltration. In the radiographic study, calcium deposits larger than 0.5 mm were observed in 40 percent of cases without an antidote, in 33 percent with triamcinolone acetonide, in 13 percent with a saline solution, and in none with thiosulfate and hyaluronidase. In the histologic study, calcium deposits were found in 53 percent of cases without antidote, 100 percent of cases with triamcinolone acetonide, 33 percent of cases with saline solution, and 13 percent of cases with sodium thiosulfate or hyaluronidase. Conclusion: Sodium thiosulfate and hyaluronidase prevent the development of calcium deposits after calcium gluconate extravasation

Recent Research in Ocular Cystinosis: Drug Delivery Systems, Cysteamine Detection Methods and Future Perspectives

Cystinosis is a rare genetic disorder characterized by the accumulation of cystine crystals in different tissues and organs. Although renal damage prevails during initial stages, the deposition of cystine crystals in the cornea causes severe ocular manifestations. At present, cysteamine is the only topical effective treatment for ocular cystinosis. The lack of investment by the pharmaceutical industry, together with the limited stability of cysteamine, make it available only as two marketed presentations (Cystaran® and Cystadrops®) and as compounding formulations prepared in pharmacy departments. Even so, new drug delivery systems (DDSs) need to be developed, allowing more comfortable dosage schedules that favor patient adherence. In the last decades, different research groups have focused on the development of hydrogels, nanowafers and contact lenses, allowing a sustained cysteamine release. In parallel, different determination methods and strategies to increase the stability of the formulations have also been developed. This comprehensive review aims to compile all the challenges and advances related to new cysteamine DDSs, analytical determination methods, and possible future therapeutic alternatives for treating cystinosisThis research was funded by Fundación Española de Farmacia Hospitalaria (FEFH 18-19), Fundación Mutua Madrileña (XVI Convocatoria de Ayudas a la Investigación en Salud) and “Asociación La Lucha de Iker”. C.M.-G. and A.F.-F. have funding research grants from Instituto de Salud Carlos III (C.M.-G.-Río Hortega CM18/00090 and A.F.-F.-Juan Rodés JR18/0004)S