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Unmasking Anticholinergic Load: When 1 + 1= 3
- Gary Kay, David L. Ginsberg, Bruce G. Pollock, Lauri J. Romanzi
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- Journal:
- CNS Spectrums / Volume 9 / Issue 12 / December 2004
- Published online by Cambridge University Press:
- 07 November 2014, p. 1
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- Article
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The cholinergic system is a major neuromodulatory neurotransmitter system, interacting with core regions of the brain and affecting learning and memory function. Cholinergic function is severely reduced in patients with pathologic conditions, such as Alzheimer's disease. Muscarinic receptors M1–M5 are located at the postsynaptic level of the central cholinergic synapse. Blockage of certain muscarinic receptors has been shown to affect cognitive functioning. The roles of the individual receptor subtypes has implications for pharmacotherapy; eg, nonselective antimuscarinic/anticholinergic medications may block muscarinic neurotransmission, causing deficits in recall and new learning, while M1-receptor agonists and M2-receptor antagonists may not interfere with cognitive functioning. Studies investigating central nervous system (CNS) depressant effects of drugs have shown that antimuscarinic agents have the potential to cause impairment of CNS functioning. CNS dysfunction may be manifested as changes in memory, disruption of sleep, hallucinations, confusion, and delirium.
Anticholinergic load refers to the cumulative effect of taking multiple drugs with anticholinergic activity. The extent to which a particular drug affects the cholinergic system can be determined by its ability to cross the blood-brain barrier, the integrity of which decreases with age. Elderly individuals are also at high risk for increased anticholinergic load due to reductions in metabolism and elimination as well as pharmacokinetic drug interactions. In addition, elderly people are often prescribed several medications that have direct anticholinergic properties and take over-the-counter medications which may also carry substantial anticholinergic burden. The cumulative effect of these medications in vulnerable elderly patients may precipitate early cognitive declines or further exacerbate cognitive deficits in those already suffering from dementia. Risk of cognitive impairment in patients with overactive bladder can thus be reduced through use of M3-selective antagonists, such as darifenacin, and via alternatives to pharmacotherapy, such as behavioral modification, pelvic floor strengthening, and bladder-retraining exercises.
Management of Overactive Bladder
- Lauri J. Romanzi
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- Journal:
- CNS Spectrums / Volume 9 / Issue 12 / December 2004
- Published online by Cambridge University Press:
- 07 November 2014, p. 8
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At least 80% of urology patients are taking several medications for any variety of other medical conditions. However, regarding treatment of overactive bladder (OAB) specifically, there are several antimuscarinic drugs available. Tolterodine and trospium chloride are, in essence, nonspecific in terms of muscarinic receptor selectivity. Solifenacin and oxybutynin show selectivity for the M1, and darifenacin is significantly M3 receptor specific (Slide 17).
The potential benefit for selective antimuscarinic agents is that they might target the bladder more specifically and avoid anticholinergic side effects in other organ systems, specifically the brain and heart. We do know that M3 receptors are also present in the intestines and in the salivary glands; thus, we might not expect organ selectivity with an M3-specific receptor because that receptor would also potentially affect the salivary gland and the intestinal tract as well.
There is a growing body of data regarding M3 activity specificity and decreased cognitive impairment in patients of various ages. This, as well as the reduction of cardiac side effects, are the major benefits of using an M3-selective anticholinergic medication rather than a nonselective agent for the treatment of OAB.