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Clonidine
Clonidine hydrochloride is an imidazoline derivative1 and an organic dichlorobenzene compound. It is a centrally acting alpha-agonist hypotensive agent1 and is distinguished among related imidazoline agents by this activity and its clinical uses. Patented in 1961 and introduced clinically in 19662, it can cause dizziness, sleepiness, dry mouth,1 and hypotension2; sudden cessation of clonidine treatment has in some cases been followed by a rapid, potentially dangerous rise in blood pressure1.
Dosage & Duration
Dosage
Doses are population estimates that vary widely between individuals.
Duration
Subjective Effects
Pharmacology
Pharmacodynamics
Clonidine is an alpha-2 agonist that lowers systemic blood pressure through central brainstem adrenergic stimulation.3 Alpha-2 receptor subtypes have been shown to inhibit adenylyl cyclase and cause hyperpolarization of noradrenergic neurons in the locus ceruleus; potassium efflux through calcium-activated channels prevents calcium entry into nerve terminals, suppressing neural firing and norepinephrine release.3 Stimulation of alpha-2A and alpha-2C receptors, found mainly in the central nervous system, may be responsible for sedation, analgesia, and sympatholytic effects.3 Clonidine may cause transient blood-pressure increases after initial dosing because of mild stimulation of peripheral postjunctional alpha-1 receptors.3
Pharmacokinetics
Clonidine is rapidly absorbed orally,3 with peak plasma levels attained in approximately 1 to 3 hours and absolute oral bioavailability of 70% to 80%.4 Food does not affect absorption.4 Less than half of an absorbed dose is metabolized hepatically, mainly by CYP2D6, with contributions from CYP1A2 and CYP3A enzymes; 4-hydroxylation is the principal metabolic reaction and produces inactive metabolites overall. Following oral administration, about 40% to 60% of the absorbed dose is recovered in urine as unchanged drug within 24 hours4 and about one-fifth is eliminated in feces. The elimination half-life is variable, generally 6-23 hours, and may be prolonged by poor kidney function; after epidural administration it is approximately 30 minutes.
Interactions
An unlisted combination is an unknown one, not a safe one. Check a dedicated combination chart before mixing.
Tolerance
Harm Potential
Addiction & Dependence
Psychological
LowClonidine is described as non-addictive with low abuse potential, although misuse has been documented in some people with pre-existing substance use disorders.
Physical
Sudden discontinuation of clonidine after prolonged high-dose treatment has been followed by reported symptoms including restlessness, palpitations, and a rapid rise in blood pressure; the data sheet advises physicians to reduce the dose gradually over 2 to 4 days when discontinuing treatment.5
Toxicity
Human lethality is rare, with a small number of reported deaths. Cardiorespiratory and central nervous system dysfunction from overdose tends to be more severe in young people than in adults.
LD50 Data
| Species | Route | Value |
|---|---|---|
| rat | oral | 126 mg/kg |
| mouse | oral | 206 mg/kg |
| rat | oral | 465 mg/kg |
Toxic or severe overdose exposure can cause cardiopulmonary instability, bradycardia, hypotension after an initial hypertensive phase, and reversible cardiac conduction defects or dysrhythmias.
Toxic or severe overdose exposure can cause respiratory depression or apnea.5
Toxic or severe overdose exposure can cause central nervous system depression with drowsiness, reduced reflexes, weakness, coma, and seizures.6
Psychosis Risk
Hallucination is listed among clonidine's psychiatric undesirable effects.5
Seizure Risk
Severe clonidine overdoses can cause seizures.7
History & Culture
Development and discovery
Seeking a better decongestant, Boehringer-Ingelheim chemist Dr. Stähle synthesized imidazoline derivatives and submitted them for evaluation by the company's medical department8. He designed clonidine by adding two chlorine atoms to the phenyl group of an imidazoline
Legality
By Country
United StatesPrescription only
AustraliaPrescription only
AustriaPrescription only
CanadaPrescription only
GermanyPrescription only
New ZealandPrescription only
PhilippinesPrescription only
SpainPrescription only
SwitzerlandPrescription only
UkrainePrescription only
United KingdomPrescription only
PolandNot scheduled
SwedenNot scheduledReferences
Citations
Article Status
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