CLASS
Alpha-2 adrenergic receptor agonist
PRESENTATION
Clear colourless solution, tablets
Formulations
- 1ml vial, 150ug, 150ug/ml
- 100, 150 microgram tablets
INDICATIONS & DOSING
Premedication, anxiolysis, sedation
- Adult; 150mcg PO
- Paediatric; 4mcg/kg PO, max 150mcg
Analgesia (acute, chronic)
Hypertension
Postoperative shivering
Substance withdrawal (alcohol, opiates/opioids, tobacco)
- Adult IV/PO; 45-300mcg, QID
- Paediatric IV/PO; 1-2mcg/kg, max 150mcg, QID
Regional anaesthesia additive (epidural > peripheral n. blockade)
- Bolus; 1mcg/kg, max 150mcg
- Infusion; 150mcg/100ml regional anaesthesia infusion (dependent on infusion rate)
PRACTICALITIES
Administration
- 150mcg clonidine in 0.9% N/saline up to 10ml; 15mcg/ml, slow IV push, titrate in ~20 minute intervals due to delayed peak effect
Practice tips
- Commence at lower PO dose range, titrate as tolerated
- Useful non-opioid analgesic adjunct
- Useful for tourniquet related sympathetic stimulation
- Anxiolytic action at low dose, but can be anxiogenic at high dose
- Not removed by haemodialysis
PHARMACOKINETICS
Onset
- IV; ~10 minutes
- Oral; 30-60 minutes, max effect 2-4 hours
- Patch; 48 hours
Duration of action
- IV; 3-7hrs
Metabolism
50% hepatic metabolism to inactive metabolites
Elimination
50% excreted unchanged renally
MECHANISM
Direct agonism of alpha-2 adrenoceptors in the locus coeruleus and spinal cord reduces sympathetic output centrally.
Alpha-2:alpha-1 selectivity 200:1.
DESIRED CLINICAL EFFECTS
Cardiovascular
- Bradycardia, hypotension (little effect on cardiac contractility)
- Reduced coronary vascular resistance
Neurological
- Sedation, MAC-sparing, reduces CMRO2
- Analgesic due to depressant activity on sympathetically-mediated pain pathways, synergistic with opioid agonism
- Inhibits post operative shivering
- Augmentation of local anaesthetic neural blockade
Gastrointestinal
- Antisialogogue
- Antiemetic
OTHER CLINICAL EFFECTS, ADVERSE EFFECTS & TOXICITIES
Respiratory
- Respiratory depressant (higher dose range)
Cardiovascular
- Hypotension, bradycardia, conduction blocks, reduced cardiac output, cardiac arrest
- Transient hypertension possible due to earlier onset vascular alpha-1 agonism
- Rebound hypertension and tachycardia on rapid cessation after prolonged therapy
Neurological
- Drowsiness
- Blurred vision
- Paradoxical anxiety, agitation, delirium
Renal & electrolytes
- Diuresis due to inhibition of ADH release (minimal effect on GFR despite reduction in renal vascular resistance)
Gastrointestinal
- Dry mouth
- Decreases gastrointestinal tone
- Mild and transient derangement in LFTs
Metabolic
- May raise plasma glucose in diabetics
Antidote
- Adrenergic receptor agonists; adrenaline, isoprenaline
- Anticholinergics; atropine
- Naloxone; transiently improves GCS and respiratory rate
CONSIDERATIONS
Precautions
- Haemodynamic compromise/sympathetically-driven physiological states
- Higher-grade cardiac conduction defects
- Renal impairment
- Elderly
Obstetric
ADEC category B3
Drug interactions
- CNS depressants; additive action
- Negative dromotropes (beta-blockers, digoxin, calcium channel-blockers); additive action
- Tricyclic antidepressants; reduce effect of clonidine
REFERENCES
Drug information has been compiled from multiple sources including
- Drugs in Anaesthesia and Intensive Care (Scarth & Smith)
- Micromedex (IBM)
- BJA Education (Oxford Academic)
- Pharmacology for Anaesthesia and Intensive Care (Cambridge)
- Australian Prescriber (NPS MedicineWise)