Cholinesterase inhibitors and the heart in old age

¹ Purvesh Madhani Senior House Officer, Gibside Unit, Centre for the Health of the Elderly, Newcastle General Hospital, Westgate Road, Newcastle upon Tyne NE4 6BE, UK
² Julian Hughes Consultant in Old Age Psychiatry, Gibside Unit, Newcastle General Hospital, Newcastle upon Tyne
³ Clive G. Ballard Professor of Age Related Disorders, Institute of Psychiatry and King’s College, London, UK

We found the review by O’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 (Proctor, 2002). The cardiovascular effects of donepezil, one of the cholinesterase inhibitors, have recently been studied (McLaren 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 (Nordberg & 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 (Ballard et al, 1998). Cholinergic inhibition is likely to make the tendency to fall greater in these patients (Ballard 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 (Pakrasi 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

1. Ballard, C. G., Shaw, F., McKeith, I., et al (1998) High prevalence of neurovascular instability in neurodegenerative dementias. Neurology, 51, 1760–1762.[Abstract/Free Full Text]
2. Ballard, C. G., Shaw, F., Lowery, K., et al (1999) The prevalence, assessment and associations of falls in dementia with Lewy bodies and Alzheimer’s disease. Dementia and Geriatric Cognitive Disorders, 10, 97–103.[CrossRef][Medline]
3. McLaren, A. T., Allen, J., Murray, A., et al (2003) Cardiovascular effects of donepezil in patients with dementia. Dementia and Geriatric Cognitive Disorders, 15, 183–188.[CrossRef][Medline]
4. Nordberg, A. & Svensson, A. L. (1998) Cholinesterase inhibitors in the treatment of Alzheimer’s disease: a comparison of tolerability and pharmacology. Drug Safety, 19, 465–480.[CrossRef][Medline]
5. O’Brien, P. & Oyebode, F. (2003) Psychotropic medication and the heart. Advances in Psychiatric Treatment, 9, 414–423.[Abstract/Free Full Text]
6. Pakrasi, S., Mukaetova-Ladinska, E. B., McKeith, I. G., et al (2003) Clinical predictors of response to acetyl cholinesterase inhibitors: experience from routine clinical use in Newcastle. International Journal of Geriatric Psychiatry, 18, 879–886.[CrossRef][Medline]
7. Proctor, A. W. (2002) Neurochemical pathology of neurodegenerative disorders in old age. In Psychiatry in the Elderly (eds R. Jacoby & C. Oppenheimer), pp. 125–149. Oxford: Oxford University Press.

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