A 75-year-old man is brought to the emergency department after a syncopal episode at his assisted living facility. The event occurred an hour ago, when he was eating lunch with other residents of the facility. The patient suddenly slumped over onto the table and awakened spontaneously after about 30 seconds. He appeared pale afterwards but was not confused, and fingerstick blood glucose was normal. Medical history includes hypertension, type 2 diabetes mellitus, benign prostatic hyperplasia, and Alzheimer disease. Temperature is 37 C (98.6 F), supine and standing blood pressure is 110/68 mm Hg, and pulse is 62/min. The oropharyngeal mucosa is moist and jugular venous pressure is normal. The lungs are clear on auscultation and heart sounds are normal. The patient is hospitalized for observation and is found to have an episodic bradyarrhythmia and atrioventricular block. If this patient's condition is due to a medication, which of the following is the most likely cause?
This patient's brief loss of consciousness is consistent with syncope, which occurs due to a transient loss of cerebral perfusion. Most episodes of syncope are benign, resulting from a vasovagal reflex that is triggered by emotional stress or prolonged standing. However, syncope may be a warning sign of a serious underlying pathology (eg, cardiac arrhythmia, severe aortic stenosis, pulmonary embolism). In addition, numerous medications can cause or contribute to syncope and should be considered.
Acetylcholinesterase inhibitors (eg, donepezil, rivastigmine) are commonly used in the management of Alzheimer dementia. Alzheimer dementia involves dysfunction of cholinergic pathways in the brain; therefore, inhibition of acetylcholinesterase and a consequent reduction in acetylcholine breakdown may improve cognitive function in some patients. However, this mechanism also produces enhanced parasympathetic tone that can lead to adverse effects. Underlying age-related degeneration of the conduction system is common in the elderly, and the effects of acetylcholinesterase inhibition can precipitate bradycardia and atrioventricular block in such patients. These conduction abnormalities lead to reduced cardiac output that may manifest as presyncope (ie, lightheadedness) or syncope.
(Choices A, B, D and E) Antihypertensive agents (eg, lisinopril) may contribute to orthostatic syncope (syncope that occurs with standing). By inhibiting vasoconstriction, these agents both prevent mobilization of venous blood that is pooled in the legs and impair the increase in arteriolar resistance needed to maintain cerebral perfusion on standing. Terazosin (used for the treatment of benign prostatic hyperplasia) and first-generation histamine-1 blockers (eg, diphenhydramine) have alpha-1 receptor-blocking properties and may also contribute to orthostatic syncope via inhibited vasoconstriction. Sodium-glucose cotransporter-2 inhibitors (eg, canagliflozin) may contribute to orthostatic syncope by stimulating an osmotic diuresis that leads to hypovolemia. None of these agents cause syncope via the slowing of cardiac conduction and they would not explain this patient's episodic bradycardia and atrioventricular block.
Educational objective:
Syncope results from a transient loss of cerebral perfusion, and numerous medications can cause or contribute to syncope. Acetylcholinesterase inhibitors (eg, donepezil, rivastigmine) may cause syncope due to enhanced parasympathetic tone that leads to bradycardia and atrioventricular block with reduced cardiac output.