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Cholinesterase inhibitors and the heart in old age

Published online by Cambridge University Press:  02 January 2018

Purvesh Madhani
Affiliation:
Gibside Unit, Centre for the Health of the Elderly, Newcastle General Hospital, Westgate Road, Newcastle upon Tyne NE4 6BE, UK
Julian Hughes
Affiliation:
Old Age Psychiatry, Gibside Unit, Newcastle General Hospital, Newcastle upon Tyne
Clive G. Ballard
Affiliation:
Age Related Disorders, Institute of Psychiatry and King's College, London, UK
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Abstract

Type
Correspondence
Copyright
Copyright © The Royal College of Psychiatrists 2003 

We found the review by Reference O'Brien and OyebodeO'Brien & Oyebode (2003) useful in its scope and breadth. It is worth emphasising that many potential cardiovascular side-effects are more likely to occur in old age. Moreover, we would add that the cholinesterase inhibitors, a class of psychotropic medication not mentioned in the review, also have important effects on the cardiovascular system.

Cholinesterase inhibitors slow the degradation of acetylcholine in the synaptic clefts, thus improving the cholinergic deficit that has been a known feature of Alzheimer's dementia (as well as other dementias) for some time (Reference Proctor, Jacoby and OppenheimerProctor, 2002). The cardiovascular effects of donepezil, one of the cholinesterase inhibitors, have recently been studied (Reference McLaren, Allen and MurrayMcLaren et al, 2003). Some of these effects are probably common to this class of drug. The study (n=15) showed that heart rate variability, which is used to assess autonomic function, is impaired by donepezil in people with neurodegenerative dementia. It also revealed a tendency for hypotensive disorders to be exaggerated.

It is known that acetylcholine affects blood pressure and heart rate through both central and peripheral means. Accordingly, some of the cardiovascular effects of cholinesterase inhibition are predictable. Central mechanisms can lead to a rise in blood pressure and a corresponding bradycardia. In patients treated with cholinesterase inhibitors, 7–13% experience peripheral cholinergic side-effects (Reference Nordberg and SvenssonNordberg & Svensson, 1998).

In older people, the risk of falls is a major concern. There is evidence that patients with Alzheimer's disease and dementia with Lewy bodies exhibit an unusually high prevalence of orthostatic hypotension and carotid sinus hypersensitivity (Reference Ballard, Shaw and McKeithBallard et al, 1998). Cholinergic inhibition is likely to make the tendency to fall greater in these patients (Reference Ballard, Shaw and LoweryBallard et al, 1999).

A retrospective study (with the advantage of being naturalistic but without controls) of 160 consecutive patients with dementia treated with cholinesterase inhibitors (Reference Pakrasi, Mukaetova-Ladinska and McKeithPakrasi et al, 2003) found that 2 patients (1.6%) experienced dysrhythmias and 1 (0.8%) experienced syncope in those treated with donepezil (n=125); 1 patient (11%) treated with galantamine (n=9) had a dysrhythmia; and 1 (3.8%) treated with rivastigmine (n=26) experienced syncope.

Thus, the potential for cholinesterase inhibitors to cause adverse cardiovascular effects and consequently falls and other serious morbidity in older people should not be overlooked.

References

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