- Treatment of hypertension
- Suppress symptoms of opioid withdrawal
- Augment sedation in the critically ill patient via infusion
- Although not superior to propofol with regards to time to extubation (JAMA, 2025)
- Analgesia:
- Treatment of acute pain (± chronic pain)
- Can be used as an adjunct in neuraxial and regional anaesthetic techniques
Clonidine
Clonidine
- Clonidine is an imidazole compound with action at ɑ2-adrenoreceptors and central imidazole receptors
Presentation
- 25 - 300μg tablets
- Colourless solution at a concentration of 150μg/ml stored in glass vials at room temperature, for IV/neuraxial/regional use
- Transdermal patch (takes 48hrs to reach therapeutic levels)
- ɑ2/ɑ1 ratio of 200:1
- Some studies suggest it is only a partial ɑ2-adrenoreceptor agonist
- Stimulates ɑ2-adrenoreceptors in:
- Lateral reticular nucleus → reduced sympathetic outflow leading to (relative) bradycardia, hypotension
- Spinal cord → augmented endogenous opioid release + modulate descending noradrenergic pathways involved in nociceptive processing
Absorption
- Rapidly and completely absorbed after oral administration; oral bioavailability 100%
Distribution
- 20% plasma protein bound
- Volume of distribution 2L/kg
Metabolism
- Metabolism: 50% metabolised in liver to inactive metabolites
Excretion
- Excretion in urine:
- 50% unchanged
- 50% inactive metabolites
- Elimination half-life is 8hrs
- Dose should be reduced in renal impairment
Cardiovascular
- Biphasic cardiovascular effect
- Initial transient increase in BP due following IV administration due to ɑ1 effects and agonism at ɑ2b receptors on vascular smooth muscle
- Following this there is bradycardia, although cardiac output tends to be maintained
- There is a lower HR for a given increase in BP due to:
- Longer PR interval
- Depressed AV nodal conduction
- Sensitisation of the baroreceptors
- Within the coronary circulation, direct vasoconstrictive effect is offset by reduced sympathetic tone
- Stabilises CV response to peri-operative stimuli
- Rebound hypertension, especially if dose >1.2g/day
Neurological
- Sedation
- Reduced MAC
- Dose-dependent effects on anxiety levels
- Low dose: anxiolysis
- High dose: anxiogenic
- Prolonged analgesia without respiratory depression when given neuraxially; acts synergistically with opioids
- Reduced post-operative opioid consumption when given IV
Renal
- Inhibits release of ADH, leading to diuresis
Gastrointestinal
- Decongestant effect
- Reduces salivary flow i.e. anti-sialogogue effect
Haematological
- Does not promote platelet aggregation despite presence of ɑ2-adrenoreceptor on platelets
- Indeed its sympatholytic effects block adrenaline-induced platelet aggregation
Endocrine
- Reduced stress response to surgical stimulus
- Inhibits insulin release although this rarely increases blood glucose