Inhibition of aAdrenergic Receptors

Inhibition of postsynaptic central and peripheral a-adrenergic receptors is a characteristic action of most TCAs. They do not inhibit b-adrenergic receptors. TCAs have a much greater affinity for a!- than a2-adrenergic receptors. Inhibition of a! receptors produces CNS sedation, orthostatic hypotension, and pupillary constriction. This action frequently offsets antimuscarinic-induced pupillary dilation. Thus, patients with TCA toxicity can present with constricted, dilated, or midpoint-sized pupils. Orthostatic hypotension is often associated with reflex tachycardia. The antihypertensive effect of clonidine can be negated by TCAs because of their ability to block the binding of clonidine to a2 receptors.

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