Main take home message is SNS overactivity/NE response (simplified). Beta 1 & 2 receptors are most dense in heart & lungs respectively vs. central/CNS alpha-2
From Lexicomp (Clondine):
Warnings/Precautions section
"Discontinuation of therapy: Gradual withdrawal is needed (taper oral immediate release or epidural dose gradually over 2 to 4 days to avoid rebound hypertension) if drug needs to be stopped. Patients should be instructed about abrupt discontinuation (causes rapid increase in BP and symptoms of sympathetic overactivity). In patients on both a beta-blocker and clonidine where withdrawal of clonidine is necessary, withdraw the beta-blocker first and several days before clonidine withdrawal, then slowly decrease clonidine. In children and adolescents, extended release formulation (Kapvay) should be tapered in decrements of no more than 0.1 mg every 3 to 7 days. The clonidine withdrawal syndrome is more pronounced after abrupt cessation of long-term therapy than after short-term therapy (1 to 2 months). It has usually been associated with previous administration of high oral doses (>1.2 mg daily in adults) and/or continuation of beta-blocker therapy. The danger of abrupt discontinuation may be increased in patients with hypertension and/or other cardiovascular considerations. Blood pressure may increase 8 to 24 hours after last dose, but has occurred 60 hours after the last clonidine dose. Rebound hypertension has occurred with discontinuation of transdermal and epidural clonidine."
MOA:
"Stimulates alpha2-adrenoceptors in the brain stem, thus activating an inhibitory neuron, resulting in reduced sympathetic outflow from the CNS, producing a decrease in peripheral resistance, renal vascular resistance, heart rate, and blood pressure; epidural clonidine may produce pain relief at spinal presynaptic and postjunctional alpha2-adrenoceptors by preventing pain signal transmission; pain relief occurs only for the body regions innervated by the spinal segments where analgesic concentrations of clonidine exist. For the treatment of ADHD, the mechanism of action is unknown; it has been proposed that postsynaptic alpha2-agonist stimulation regulates subcortical activity in the prefrontal cortex, the area of the brain responsible for emotions, attentions, and behaviors and causes reduced hyperactivity, impulsiveness, and distractibility. Epidurally administered clonidine produces dose-dependent analgesia not antagonized by opiate antagonists. The analgesia is limited to the body regions innervated by the spinal segments where analgesic concentrations of clonidine are present. Clonidine is thought to produce analgesia at presynaptic and postjunctional alpha-2-adrenoceptors in the spinal cord by preventing pain signal transmission to the brain."