From the Guidelines

First-generation antihistamines are diphenhydramine, hydroxyzine, and chlorpheniramine.

These medications are associated with sedation, impairing driving ability and leading to cognitive decline, particularly in elderly patients 1.
They can cause anticholinergic effects, including dryness of mouth and eyes, constipation, inhibition of micturition, and an increased risk for provocation of narrow-angle glaucoma 1.
Cyproheptadine has dual function as a sedating H1R blocker and a serotonin receptor antagonist and has been used to treat diarrhea and nausea in the setting of MCAS 1.
Ketotifen, also a sedating agent, is now available as a compounded medication in the United States and is used to treat dermatologic, gastrointestinal, and neuropsychiatric symptoms 1.
First-generation antihistamines have significant potential to cause sedation, performance impairment, and anticholinergic effects, making second-generation antihistamines generally preferred for the treatment of allergic rhinitis 1.
Older adults are more sensitive to the psychomotor impairment promoted by first-generation antihistamines and are at increased risk for complications such as fractures and subdural hematomas caused by falls 1.

From the Research

First-generation antihistamines are a class of medications that cross the blood-brain barrier, potentially causing sedation and impairing cognitive function and psychomotor performance 2, 3.
They have been in use for more than 6 decades and have poor receptor H1-receptor selectivity, leading to various adverse events such as anti-muscarinic, anti-α-adrenergic, anti-serotonin, and sedative effects 3.
These medications are highly effective in treating hyperhistaminic conditions but frequently induce sedation and may adversely affect a child's learning ability 4.

Second-generation antihistamines, such as cetirizine, desloratadine, fexofenadine, levocetirizine, and loratadine, cross the blood-brain barrier to a significantly smaller extent than first-generation antihistamines 2.
They are highly selective for the histamine H1-receptor, have minimal adverse events, and are considered the antihistamines of choice for treating allergic rhinitis, allergic conjunctivitis, and urticaria 2, 3.

The risks of first-generation antihistamines have been underestimated, particularly when purchased as nonprescribed over-the-counter medications by the public 3.
First-generation antihistamine-induced sedation has been described to occur in more than 50% of patients receiving therapeutic dosages, and serious adverse events are unusual but can be life-threatening 4.
The availability of newer generation antihistamine compounds has added to the clinical effectiveness and patient tolerance of a widely prescribed class of drugs, with improved safety profiles, particularly in the case of third-generation antihistamine overdose 4.