Clonidine exerts its action through stimulation of central alpha 2-adrenergic receptors, leading to decreased sympathetic outflow from the central nervous system (CNS) as well as reduced peripheral resistance, heart rate, and blood pressure. Therapeutic uses for clonidine include the treatment of Attention Deficit Hyperactivity Disorder (ADHD), Tourette’s syndrome, conduct and oppositional disorder, hypertension, narcotic withdrawal, cancer-related pain, and delirium tremens. Clonidine is available as transdermal patches (0.1 mg/day, 0.2 mg/day, 0.3 mg/day), immediate-release tablets (0.1, 0.2, 0.3 mg), an extended-release tablet (0.1 mg), compounded oral suspension, intravenous (IV) solution (5 mg/mL), and epidural solution (0.5 mg/mL, 0.1 mg/mL).
The toxic dose of clonidine varies; 0.1 mg has produced toxic effects in children, and dosing just above the therapeutic range can cause toxicity in adults. The onset of effects is typically about 30 minutes, with peak effect 6-12 hours following ingestion. Clinical presentation of intoxication includes lethargy, somnolence, coma, pupil constriction, apnea, bradycardia, and hypotension. Recovery of the CNS and respiratory effects is typically seen within 24 hours with supportive care; however, bradycardia and hypotension may persist due to clonidine’s long half-life.
Mental status
Children can become unresponsive following clonidine ingestion, but often arouse in response to stimuli.4 One theory is that clonidine increases endogenous opioid release, leading to effects similar to an opioid overdose. Following clonidine ingestion of as little as one to two tablets, patients are at risk of severe CNS depression, which can lead to intubation.
Airway/Breathing
In a review of single-drug ingestions that resulted in endotracheal intubation, clonidine was the drug that most frequently resulted in intubation in children less than 6 years old.5
Cardiovascular Effects
Clonidine exerts its action on alpha-adrenergic and imidazoline receptors. Alpha-2 adrenergic action decreases norepinephrine release, lowering blood pressure. In very high serum concentrations, peripheral alpha-1 receptors can be stimulated, leading to the release of norepinephrine, causing vasoconstriction and hypertension. Hypertension is usually transient, overcome by the centrally mediated sympathetic inhibition to cause hypotension. Additionally, clonidine is thought to increase the release of beta-endorphin, which causes hypotension and bradycardia. Bradycardia can occur due to increased vagal tone with decreased sympathetic outflow.2 Bradycardia and hypotension are generally responsive to supportive care, which includes atropine for symptomatic bradycardia, IV fluids, and sometimes vasopressors like norepinephrine for hypotension.
Naloxone is an opioid competitive antagonist that was developed to counter the effects of opioid overdose.4 Several case reports have reported observations of reversal of somnolence secondary to naloxone administration in clonidine overdose. Naloxone was administered in some of these cases, as clonidine toxicity was mistaken for opioid toxicity. The proposed mechanism for naloxone in clonidine toxicity is the reversal of the effects of beta-endorphin or the reversal of endogenous opioids.1,4 Seger and Loden evaluated naloxone administration to children following clonidine ingestion. In this study, sedation resolved in 35 (87.5%) patients after being treated with naloxone following a clonidine ingestion. Naloxone doses ranged from 3.5 mg to 10 mg.4
In clonidine overdose, administer high-dose naloxone to avoid intubation secondary to CNS depression.
0.1 mg/kg (maximum 2 mg/dose) repeated every 1-2 minutes with a total maximum dose of 10 mg.4
Withdrawal
In patients with chronic use of opioids, large doses of naloxone should be avoided due to the risk of precipitating withdrawal. In opioid naive patients who have ingested clonidine, withdrawal is not a concern.
Call the Utah Poison Control Center at 1-800-222-1222 at any time, 24/7, for assistance in managing known or suspected clonidine poisonings.