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Question 2#

Which of the following antimuscarinics has the least central nervous system side effects?

A. Oxybutynin
B. Trospium chloride
C. Solifenacin
D. Darifenacin
E. Tolterodine

Correct Answer is B

Comment:

Answer B

Whilst antimuscarinic agents are the mainstay of pharmacological treatment of overactive bladder syndrome, their use can be limited by side effects. Central nervous system effects are particularly important in the elderly population as the structure of the blood brain barrier may be impaired due to stroke, Alzheimer’s disease or diabetes. Central nervous system side effects include headache, dizziness or tiredness. These may be determined by the ability of the antimuscarinic agent to cross the blood brain barrier, the specificity for muscarinic receptors or actions of metabolites. Antimuscarinics are described as tertiary (e.g., oxybutynin) or quaternary amines (e.g., trospium chloride). Tertiary amines are lipophilic and are more likely to cross the blood brain barrier compared with quaternary amines which are, in theory, associated with fewer central nervous system side effects. All the tertiary amines (darifenacin, tolterodine and solifenacin) may cause cognitive side effects and exacerbating the anticholinergic burden but oxybutynin seems to be the one with the most negative effect on cognitive function. All five muscarinic receptors are found in the brain. M1 and M2 receptors are associated with memory and cognition whereas M3 receptors (which are clinically significant for detrusor contraction) have a low expression in the brain. Antimuscarinics, which have receptor specificity for M3 receptors, in theory, should have a lower risk of cognitive side effects.

Further Reading:

• Wagg A, Verdejo C, Molander U. Review of cognitive impairment with antimuscarinic agents in elderly patients with overactive bladder. Int J Clin Pract,  2010 Aug; 64(9): 1279–1286.
• Chancellor M, Boone T. Anticholinergics for overactive bladder therapy: Central nervous system effects. CNS Neurosci Ther, 2012 Feb; 18(2): 167–174.