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These antihistamines are more selective on peripheral H1 receptors and have a lower affinity for cholinergic and alpha-adrenergic receptor sites, which reduces the risk of anticholinergic and central nervous system side effects. Considerations for Older Adults. Older adults are especially sensitive to the central nervous system- and anticholinergic-related side effects of sedating antihistamines because of decreased cholinergic neurons or receptors in the brain, reduced hepatic and renal function, and increased blood-brain permeability. These patients also often have coexisting conditions and often take multiple medications that increase the risk of drug-drug interactions and the potential for sedative adverse effects. Even when first-generation antihistamines are used at the lowest doses recommended by the manufacturer, they can cause serious central nervous system side effects, including dizziness, hypotension, and next-day sedation. These side effects can greatly increase the risk of falls and fall-related injury, with the impact of even one fall in an older adult potentially having tremendous negative consequences, including diminished quality of life and loss of independence.

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