Can ophthalmic drops cause central nervous system depression and cardiogenic shock in infants?

Topical ocular medications have been widely prescribed and successfully used in children for the management of different ophthalmic disorders. We present 2 infants admitted to our pediatric intensive care unit who developed altered state of consciousness, hypotonia, hypothermia, bradycardia, and apnea after instillation of ophthalmic drops. The second infant also had hypotension and broncho-obstruction. Few days before admission, both infants were diagnosed with congenital glaucoma, and topical antiglaucoma treatment was initiated. Ophthalmic drops with brimonidine and brinzolamide were prescribed to both patients, whereas the second infant also received topical timolol. After elimination of other possible causes, the diagnosis of intoxication with topical antiglaucoma medications was established. After discontinuation of eye drops and vigorous symptomatic treatment, both infants recovered without sequels. Topically applied ophthalmic drops may cause life-threatening systemic adverse effects in infants, such as central nervous system depression and cardiogenic shock. Moreover, these 2 patients illustrate the importance of careful evaluation of all topical medications and their consideration as possible causes of the derangements in critically ill infants.

Timolol side effects and inadvertent overdosing.

The case reports demonstrate that significant and potentially dangerous side effects from timolol maleate occur as a result of inadvertent overdosing. Because many glaucoma patients are elderly and vision is frequently impaired, overdosing may be the mechanism of side effects in many patients especially the elderly. A simple dropper that would withdraw only one drop and deliver the same would resolve this problem.

Calcium interferes with the cardiodepressive effects of beta-blocker overdose in isolated rat hearts.

Propranolol, timolol and sotalol were compared with respect to their cardiotoxic properties in isolated, spontaneously beating rat hearts. Propranolol and timolol induced a dose-dependent decrease in myocardial contractility. A high dose of sotalol had only modest negative inotropic effects. Similar reductions in myocardial contractility were observed in isolated, ventricle-stimulated rat hearts. These observations were similar to those in a previous study in which spontaneously beating and ventricle-stimulated reserpinized rat hearts were investigated. Spontaneously beating rat hearts were perfused with a high-, a normal- and a low-Ca++ medium, each with and without propranolol, timolol and sotalol. Addition of each beta-blocker to a normal-Ca++ medium induced a decrease of myocardial contractility and of heart rate and an increase of AV-conduction time when compared with the drug-free medium. In a high-Ca++ medium containing the same concentration of each beta-blocker, a less pronounced decrease of myocardial contractility was observed. Heart rate decreased and AV-conduction time increased to the same extent as after perfusion with the drug containing normal-Ca++ medium. With respect to the corresponding drug-free medium perfusion with a low-Ca++ medium with each beta-blocker enhanced the decline in myocardial contractility, most pronounced in propranolol and timolol containing media. For propranolol and sotalol the decrease in heart rate and increase in AV-conduction time were similar to the results after administration of the same beta-blocker in a high- and a normal-Ca++ perfusion media. Timolol caused an electromechanical dissociation. It was concluded that in beta-blocker intoxication the negative-inotropic phenomena cannot be explained by an action of the drugs on the beta-receptor since the results in reserpinized and non-reserpinized rat hearts were similar. Other effects have to be responsible for the observed cardiotoxic phenomena. The present results indicate that these phenomena can be influenced by Ca++ and or can be attributed to differences in lipophilicity.