LAUSR

Decreased levels of acetylcholine contribute to cognitive dysfunction in Alzheimer’s disease (AD). Acetylcholinesterase (AChE) inhibitors prevent the degradation of acetylcholine by inhibiting the enzyme AChE, resulting in increased levels of acetylcholine in the synaptic endings. In Japan, galantamine (16–24 mg/day) has been used for the treatment of mild-to-moderate AD since 2011. Not only is it a long-acting, selective, reversible, and competitive AChE inhibitor, but it also modulates presynaptic nicotinic receptors. An 87-year-old man with AD was transported to the Emergency Medical Center and Poison Center at Saitama Medical University Hospital (Moroyama, Japan) after his family had found him to be unresponsive early in the morning. He had been prescribed ambroxol hydrochloride (45 mg/day) and pravastatin sodium (10 mg/day) for chronic bronchitis and hyperlipidaemia, respectively, for a long period. Approximately 2 years before presenting to us, he had been diagnosed with mild AD and prescribed 8-mg galantamine daily; 6 months later, this was increased to 16 mg and then to 24 mg (a 12-mg tablet twice a day at 0800 hours and 2000 hours) another 6 months later. During the previous 2 months, he had an unsteady gait and fell twice. The day before presentation, he took a 12-mg galantamine tablet at 2000 hours. On admission, at about 0800 hours, he was drowsy with a consciousness level of E3V4M6 on the Glasgow Coma Scale and had miosis (diameters of both pupils: 1.5 mm). When called loudly, he faintly opened his eyes and complained of nausea. His vital signs were as follows: blood pressure, 140/80 mmHg; pulse rate, 54 bpm (sinus rhythm); respiratory rate, 18/min; SpO2, 98% breathing room air; and body temperature, 36.0 C. Physical examination revealed excessive salivation and enhanced bowel sounds. Initial blood tests, including butyrylcholinesterase (BChE) activity (261.2 IU/L, normal range: 217–491 IU/L), were unremarkable. Computed tomography of the brain demonstrated moderate brain atrophy. A provisional diagnosis of acute cholinergic syndrome caused by galantamine was made, and the patient was treated with fluid infusion. Three hours after admission, he remained drowsy with miosis (diameters of both pupils: 1.5 mm) and sinus bradycardia (54 bpm). Because he was alert, all other symptoms resolved 6 h after admission (diameters of both pupils: 2.5 mm; pulse rate: 67 bpm (sinus rhythm)), and both salivation and bowel sounds were normal, he was discharged 7 h after admission. To determine whether acute cholinergic syndrome resulted from poisoning or an acute adverse reaction, blood samples stored at −80 C were analyzed. Serum galantamine concentrations at 12, 15, and 18 h after the last ingestion of galantamine were 35.0 ng/mL, 29.9 ng/mL, and 22.7 ng/mL, respectively, as determined by liquid chromatography–mass spectrometry (LCMS-8060; Shimadzu Corporation, Kyoto, Japan). The serum elimination half-life of galantamine was calculated to be 9.6 h. The maximum serum concentration during a dose interval at steady state (Cmax,ss) was calculated to be 75.1 ng/ mL, as the patient had consistently taken a 12-mg galantamine tablet twice a day at a 12-h interval for a year. Also, the pharmacokinetic data for Reminyl published by Janssen Pharmaceutical K.K. (Tokyo, Japan) reported that the time at Cmax,ss was 1 h. Acute cholinergic syndrome results from poisoning or an acute adverse reaction due to AChE inhibitors such as carbamates with features of muscarinic, nicotinic, and central muscarinic symptoms. Although there have been no reports describing acute cholinergic syndrome associated with galantamine, a few case reports described symptoms related to AChE inhibition, such as urinary incontinence, QT interval prolongation, and complete atrioventricular block. It is possible that acute cholinergic syndrome associated with galantamine has been overlooked. In the present case, the patient developed acute cholinergic syndrome exhibiting muscarinic symptoms including miosis, sinus bradycardia, excessive