Clonidine is a 40-year-old medication in the class of antihypertensive medications which act on alpha-adrenergic and imidazoline receptors agonist. Clonidine is an anti-hypertensive drug that lowers blood pressure and heart rate by relaxing the arteries and increasing the blood supply to the heart; it has other FDA-approved indications such as:
Clonidine has multiple off-label uses such as the management of withdrawal symptoms from opioids, benzodiazepines, and alcohol, and for treatment of anxiety, insomnia, and post-traumatic stress disorder (PTSD).
Because of the effect of clonidine on the sympathetic nervous system specifically, the reduction the epinephrine in circulation, it has been used in many other aspects of medicine, for example, control of hot flashes in menopause, restless leg syndrome, and prophylaxis of vascular migraine headaches. Also, there is a test for phaeochromocytoma that is called the clonidine suppression test, in the lab, they measure the catecholamine levels before and after a dose of oral clonidine which, in healthy people, should cause the decrease in the level of catecholamines in circulation.
Clonidine hydrochloride is an imidazoline derivative that acting centrally on alpha-2 adrenergic as an agonist. The chemical name for clonidine is 2-((2,6-dichlorophenyl) amino)-2-imidazoline hydrochloride.
Clonidine as an alpha-adrenergic agonist in nucleus tractus solitarii (NTS) excites a pathway that inhibits excitatory cardiovascular neurons. Clonidine has alpha-antagonist effect in the posterior hypothalamus and medulla. The final response is reduced sympathetic outflow from the central nervous system (CNS) which clinically causes the decrease arterial blood pressure.
One of the theories about the mechanism of action of clonidine in the management of pain in the CNS is that many pain signals occur in the dorsal horn of the spinal cord and are sent to higher centers of the CNS. There is a release of norepinephrine from the descending inhibitory bulbospinal neurons that binds to alpha-2-receptors in the dorsal horn to decrease afferent pain transmission and produces analgesia. Therefore, drugs like clonidine that target alpha-2 receptors can influence the transmission of pain.
Epidural clonidine used as an adjunct to local anesthetics has three different mechanisms of action. First, stimulation of alpha-2-receptors in the dorsal horn reduces the pain transmission. Secondly, clonidine can cause local vasoconstriction that limits vascular removal of local epidural anesthetics. Lastly, clonidine enhances neuraxial opioids, and in combination with fentanyl, interacts in an additive manner, which can reduce the dose of each component by 60% for postoperative analgesia.
The exact mechanism of action of clonidine in the management of attention-deficit hyperactivity disorder (ADHD) is not clear, but it is possible prefrontal cortex brain activity is involved.
Clonidine Forms and Dosages
Transdermal Patch (extended-release)
Extended-release and immediate release types of clonidine are not to be used interchangeably.
In cases of conversion from oral to transdermal clonidine recommendation is:
Renal Impairment Dosing Modification
For renal impairment, it is recommended to start a low dose and titer up with caution. The initial dose should consider the amount of renal impairment. Monitor carefully for hypotension and bradycardia.
Clonidine like any other medications has a potential for short-term and long-term side effects. Some of the common side effects based on FDA reports include:
Common Reactions (tend to resolve with continued therapy)
Note rebound hypertension and withdrawal symptoms if medication discontinued immediately.
Hypersensitivity to medication, class of alpha-2-agonist. For epidural use: administration above C4 dermatome. Do not discontinue suddenly otherwise there is a risk of rebound hypertension and withdrawal symptoms. Dose adjustment in renal impairment, cardiovascular, bradycardia, hypotension, and severe coronary artery disease (CAD) patients. Also use with caution in patients with a history of depression, recent myocardial infarction (MI), and syncope.
Clonidine has a black box warning for appropriate use.
Obstetrical, Postpartum, or Perioperative Use
Even though clonidine is a medication that commonly used for withdrawal symptoms of opioid addiction, itself has a potential to be the substance of abuse, and need to be a monitor in that regard.
Clonidine use in many cases does not typically fit the category of addiction stereotype, especially because most of the abusers do not feel like they are doing anything wrong as it is a prescription medication. Clonidine is not in a category of high potential for abuse medication by the United States government, and as a result, it has much less restriction, and it is less risky to take it for abuse. Unfortunately, many of clonidine abuse starts in rehabilitation centers as it is a common medication for opioid and alcohol withdrawal treatment. Since it helps to reduce the withdrawal symptoms and craving, clinicians should evaluate their concerns about the potential of trading the addictions. Also, the synergistic potential of clonidine when mixed with other benzodiazepines, opioids, or alcohol, can give the individual more potent drowsiness and detachment from reality even further. It is important to notify the patients and try to screen for signs of dependency to clonidine as listed below: