verse effects in this group of patients. From a pool of more than 1,000 patients with myasthenia gravis treated with ChE inhibitors, Arsura and colleagues (1987) present detailed clinical descriptions of drug-related hypotensive events in 12 patients (7 men, 5 women, mean age 62.6 years). Among these 12 case studies, 8 hypotensive events occurred after edrophonium, 2 after neostigmine, and 2 after PB. The proximal causes of documented syncopal or near-syncopal episodes were severe sinus bradycardia, junctional bradycardia, or complete atrioventricular (A-V) dissociation in nine patients and paradoxic sinus tachycardia in two others. None had obvious preceding signs of cholinergic excess, but all 12 patients had documented new exposure to or upward dose adjustment of their AChE-inhibiting medications, temporally consistent with the onset of the hypotensive episode. Also, the patients showed a strong tendency to respond to atropine and/or to reduce or discontinue use of the anticholinesterase drug, arguing against myasthenia gravis as the primary cause of the adverse event. Based on this review of more than 1,000 patients with myasthenia gravis treated with AChE inhibitors, the estimated frequency of such drug-related syncopal or presyncopal events is approximately 1 percent. The authors advise extreme caution in the use of this class of medications in all patients with pre-existing conduction defects and in the elderly, the groups that seem most prone to medication-precipitated hypotensive episodes.

Considerable clinical experience of adverse cardiovascular events also exists in relation to the use of AChE inhibitors for postanesthesia reversal of non-depolarizing muscle relaxants (e.g., d-tubocurare and pancuronium). Owens and colleagues (1978) studied 93 elderly patients (age > 65 years) undergoing general anesthesia for elective surgery. In this setting, 43 patients were treated with neostigmine and atropine and 50 with PB and atropine (all agents administered intravenously), and monitored for 90 minutes for the occurrence of postoperative cardiac dysrhythmias. Twenty-three percent of all patients experienced abnormal cardiac rhythms. Among those treated with neostigmine, 35 percent exhibited arrhythmias compared to 14 percent among the PB group, a statistically significant difference. The most commonly observed dysrhythmias were due to prolonged atrioventricular conduction resulting in bradycardia or A-V block. The authors concluded that the muscarinic effects of PB are associated with fewer cardiac side effects than those of neostigmine.

Arad and colleagues (1992a) explored the cardiovascular effects of PB on eight hypertensive patients treated with beta-adrenergic blockers (propranolol and atenolol). In this double-blind, crossover study, patients were treated with 30 mg of oral PB or placebo three times daily for 2 days. PB caused no significant effect on heart rate, plasma catecholamine levels, or resting blood pressure. Both systolic and diastolic blood pressure increased with exercise intensity, although a small but statistically significant decrease in diastolic blood pressure with exercise was noted during PB treatment. The authors attributed this to a mild decrease in peripheral vascular resistance (PVR) induced by the parasympathomimetic action of PB. Given the fact that patients with essential hypertension demonstrate increased PVR and that beta-blockers tend to further increase

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