Distigmine Bromide

Galantamine is a cholinesterase inhibitor employed in Alzheimer's disease management. Cholinesterase inhibitors are associated with potential cholinergic side effects that, when severe, can result in cholinergic crises. Although crises induced by other cholinesterase inhibitors, such as distigmine and rivastigmine, have been reported, cases of galantamine-induced cholinergic crises remain undocumented. This study presents a case of cholinergic crisis triggered by galantamine overdose in an 89-year-old woman weighing 37 kg with Alzheimer's disease history, even though her serum cholinesterase levels were normal. The patient overdosed on 264 mg of galantamine, leading to rapid deterioration, marked by restlessness, tremors, sweating, diarrhea, pharyngeal gurgling, and severe hypoxia. Upon arrival at the emergency department, the patient exhibited pinpoint pupils, compromised airway, and low oxygen saturation, necessitating immediate intubation and transfer to the intensive care unit. After 72 h, the patient successfully recovered and was weaned off mechanical ventilation, maintaining normal serum cholinesterase levels. Animal studies suggest a lethal galantamine threshold of 3 to 6 mg/kg in humans. Unlike other cholinesterase inhibitors that typically reduce serum cholinesterase levels during cholinergic crises, galantamine appears to selectively inhibit acetylcholinesterase, possibly sparing butyrylcholinesterase. This selectivity may explain the normal serum cholinesterase levels.

An in-line smartphone connected to a screen-printed selective electrode hand-held device was used to determine the concentration of distigmine bromide (DB) in its pure and dosage forms as well as its degradation kinetics by continuously measuring the change in the produced emf over time. The main objective, supported by the data presented, is to produce a highly reliable smartphone integrated selective sensor as a portable analyzer with potential high cloud connectivity combining a wide linear dynamic range, the fastest response time with the lowest limits of detection and quantitation while best integrating green analytical chemistry principles. The choice of ionophore used in this approach was guided by computation and the data obtained was compared with traditional analytical techniques. DB, for which there are no previously reported stability-indicating methods and for which four novel such methods are proposed here, was selected as a model drug for this work. At-line UV-spectrophotometry DB assay was obtained by measuring the difference between the spectra of the degradation product and the same concentration of intact drug. The degradation kinetics were studied by this method through tracking the decrease of DB absorbance and/or the increase of a generated degradation product signal over time. Off-line separation based HPLC and TLC stability-indicating methods for DB were also presented. All methods employed in this work were validated for accuracy, precision, specificity, repeatability, linearity, range, detection and quantification limits according to the ICH guidelines and were applied to the analysis of laboratory prepared mixtures as well as commercial products. While all methods proposed were shown to be highly reliable, the smartphone integrated selective sensor is highlighted as a portable analyzer with potential high cloud connectivity and was shown to combine a wide linear dynamic range, the fastest response time with the lowest limits of detection and quantitation while best integrating green analytical chemistry principles.