Which of the following effects accounts for the major toxicity of tricyclic antidepressants?

The major toxicity of tricyclic antidepressants (TCAs) is primarily related to their anticholinergic effects. These medications tend to block acetylcholine receptors, which can lead to a variety of side effects such as dry mouth, constipation, urinary retention, blurred vision, and cognitive disturbances, particularly in older adults who may be more sensitive to these effects.

In addition to the anticholinergic toxicity, TCAs can also affect other neurotransmitter systems, but the cholinergic effects are particularly significant because they can lead to severe complications, including confusion, delirium, and even life-threatening situations in cases of overdose.

While serotonergic, dopaminergic, and adrenergic effects contribute to the therapeutic profile and side effects of TCAs, it is the cholinergic effects that stand out as the major concern in terms of toxicity.