Final answer:
Orthostatic hypotension associated with TCAs is caused by the blockade of alpha-1 adrenergic receptors, which reduces the body's ability to regulate blood pressure upon standing.
Step-by-step explanation:
Orthostatic hypotension associated with tricyclic antidepressants (TCAs) is primarily caused by the blockade of alpha-1 adrenergic receptors. TCAs can inhibit the reuptake of norepinephrine (NE), and at the same time, block alpha-1 receptors, which are responsible for vasoconstriction. The inhibition of these receptors reduces the body's ability to rapidly adjust to a standing position from a sitting or lying position, leading to a drop in blood pressure upon standing, known as orthostatic hypotension.
While the main role of TCAs is to elevate mood by preventing the reuptake of neurotransmitters like serotonin and norepinephrine, their non-selective mechanism of action means they also affect other neurotransmitter systems, like the cholinergic and histaminergic systems, which can contribute to various side effects.