Of note, patients who ingest large amounts may initially have early hypertension, which then progresses to hypotension. Alteration in the level of consciousness usually presents within the first one and a half hours, preceding any cardiovascular effects, which usually present within 4 hours.

Poisoning with clonidine classically presents with somnolence, respiratory depression, hypotension, bradycardia, and miosis. Additionally, clonidine has been shown to affect GABA levels by several different mechanisms, which clearly play a role in sympathetic/parasympathetic regulation.

Clonidine’s effect on nitric oxide production in the endothelial cells and the subsequent vasodilation has also been discussed. I-1 receptors are also found peripherally in the plasma membranes of the heart and kidneys and cause a decrease in peripheral vascular resistance, heart rate, and cardiac contractility.

In tandem with this, Imidazoline-1 receptors in the rostral ventrolateral medulla, which have a high affinity for clonidine, compound the inhibition of sympathetic neurotransmission when activated by clonidine. The inhibition of the LC also contributes to the decrease in circulating norepinephrine and indirectly contributes to the hypotension and bradycardic effects. Clonidine’s inhibitory effect on the LC causes disinhibition of the ventrolateral preoptic nucleus, which is responsible for the drug's sedative effect. A-2 receptors are also found in the locus coeruleus (LC), which plays a large role in autonomic function and states of arousal. This inhibition then reduces sympathetic tone throughout the body, particularly decreasing the level of vasoconstriction, causing hypotension and bradycardia. By activating the presynaptic alpha-2 adrenergic receptors of the central nervous system, specifically in the rostral ventrolateral medulla and the nucleus tractus solitarii, the release of norepinephrine (NE) into neuronal synapses is inhibited.

These receptors have been found to work in tandem to produce the hypotensive effects of clonidine. As mentioned, clonidine is an alpha-2 receptor and imidazoline-1 receptor agonist.

Benzo overdose antidote