Clonidine
Centrally-acting alpha-2 adrenoceptor agonistFor exam revision only — verify all doses against the current BNF, the SmPC and your local formulary before clinical use. Disclaimer
Summary
Centrally-acting alpha-2 adrenoceptor agonist with sedative, anxiolytic, analgesic, sympatholytic and anti-shivering effects; opioid- and anaesthetic-sparing.
Indications & Dosing
- Premedication / sedation
Oral 1-5 micrograms/kg; IV 1-2 micrograms/kg (slow).
- Hypertension
Oral 50-100 micrograms BD-TDS.
- Neuraxial adjunct
Epidural / intrathecal 1-2 micrograms/kg.
- Anti-shivering
IV 0.5-1 microgram/kg.
Contraindications
- Severe bradyarrhythmia, sick sinus syndrome, or 2nd/3rd-degree AV block.
- Never stop abruptly after chronic use - rebound hypertension.
Formulations
- Tablets
25, 100, 300 microgram.
- Injection
150 microgram/mL.
Structure & Chemical Properties
- Class
Imidazoline derivative.
- pKa
8.3 (weak base).
- Lipid solubility
High - rapid CNS penetration.
The imidazoline ring confers central alpha-2 selectivity (~200:1 alpha-2:alpha-1).
Effect Timings
- Onset
IV 5-7 min; oral 30-60 min.
- Peak effect
Oral 60-90 min.
- Duration
6-10 h.
Absorption
- Oral bioavailability
75-95%.
Distribution
- Protein binding
20-40%.
- Vd
2 L/kg.
Metabolism
- Site
Hepatic (~50%).
- Metabolites
Inactive.
Elimination
- Terminal t-half
12-16 h (prolonged in renal impairment).
- Clearance
Renal - 40-60% excreted unchanged.
Mechanism of Action
Agonist at central pre-synaptic alpha-2 adrenoceptors (locus coeruleus, dorsal horn), reducing noradrenaline release and central sympathetic outflow; partial imidazoline-receptor binding contributes.
Systemic Effects
- CNS
- Sedation and anxiolysis with minimal respiratory depression.
- Analgesia and opioid-sparing.
- Reduces anaesthetic (MAC) requirements.
- CVS
- Bradycardia and reduced cardiac output.
- Hypotension from central sympatholysis; transient hypertension after rapid IV (peripheral alpha-2).
- RS
Minimal respiratory depression; airway reflexes preserved.
- GI
Dry mouth (reduced salivation); reduced GI motility.
- RenS
Mild diuresis and natriuresis.
- Other
Anti-shivering; attenuates opioid and alcohol withdrawal.
Side Effects & Toxicity
- Rebound hypertension on abrupt withdrawal.
- Bradycardia, hypotension, dry mouth, sedation.
- Overdose mimics opioid toxicity: bradycardia, hypotension, CNS depression.