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CLONIDINE

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)

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