Clonidine is an Alpha-2 (α2) Adrenergic Receptor Agonist
Clonidine is an α2-agonist, making option (c) the correct answer. 1, 2, 3
Mechanism of Action
- Clonidine acts primarily as an agonist at alpha-2 adrenergic receptors throughout the brain, with some activity at imidazoline I1 receptors 2
- It stimulates alpha-2 adrenoreceptors in the brain stem, resulting in reduced sympathetic outflow from the central nervous system 3
- In the prefrontal cortex, postsynaptic alpha-2 agonism enhances noradrenergic neurotransmission, strengthening the regulatory role of the prefrontal cortex in attention, thought, and working memory 1, 2
- Clonidine's chemical name is 2-(2,6-dichlorophenylamino)-2-imidazoline hydrochloride, and it exists as an imidazoline derivative 3
Pharmacological Properties
- Clonidine has a higher potency compared to guanfacine (approximately 10 times more potent) but less selectivity for alpha-2A receptors 1, 4
- The drug is primarily metabolized via CYP2D6 and excreted both renally and hepatically in equal shares 1
- Following oral administration, clonidine displays biphasic disposition with a distribution half-life of about 20 minutes and an elimination half-life ranging from 12 to 16 hours 3
- Peak plasma clonidine levels are attained in approximately 1 to 3 hours after oral administration 3
Clinical Effects
- Clonidine reduces peripheral vascular resistance, renal vascular resistance, heart rate, and blood pressure 3, 5
- The patient's blood pressure typically declines within 30 to 60 minutes after an oral dose, with maximum decrease occurring within 2 to 4 hours 3
- Slowing of the pulse rate has been observed in most patients given clonidine 3
- Clonidine does not alter normal hemodynamic response to exercise 3
Differentiation from Other Adrenergic Agents
- Unlike alpha-1 agonists (option a), which cause vasoconstriction and increased blood pressure, clonidine's central alpha-2 agonist effects lead to decreased sympathetic outflow and lower blood pressure 5, 6
- Alpha-1 antagonists (option b) block alpha-1 receptors in blood vessels, causing vasodilation, while clonidine works primarily through alpha-2 receptor stimulation 5
- Beta-1 agonists (option d) increase heart rate and contractility, whereas clonidine typically decreases heart rate 3
- Beta-2 agonists (option e) cause bronchodilation and vasodilation in skeletal muscle, effects not associated with clonidine 3, 7
Clinical Applications
- Clonidine is used in the treatment of hypertension due to its central sympatholytic effects 3, 6
- It has applications in ADHD treatment, with a recommended starting dose of 0.1 mg at bedtime 1, 2
- Clonidine is used in the management of opioid withdrawal symptoms 8
- It can potentiate the effects of local anesthetics when used in regional anesthesia 9
- Clonidine has been used in the treatment of PTSD-associated nightmares 1
The FDA drug label clearly identifies clonidine as "a centrally acting alpha-agonist hypotensive agent" 3, confirming its classification as an alpha-2 adrenergic receptor agonist.