CLONIDINE

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• CLONIDINE

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email anaesthesia.co.in_at_gmail.com
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• centrally acting selective, partial alpha
  adrenergic agonist (2201 alpha2 to alpha1)
• Stimulates inhibitory alpha2 adrenoceptors to
  reduce central neural transmission in spinal
  neurons

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• Commercial Availability- as preservative- free
  Clonidine HCl 150µg/ml solution single dose
  ampoules
• Storage- below 25C
• Mechanism of action
• produce clinical effects by binding to alpha2
  receptors.
• 3 subtypes
• alpha2A- mediate sedation, analgesia,
  sympatholysis.
• alpha2B- vasoconstriction and possibly
  antishivering effects.
• alpha2C- may be responsible for startle response.

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• PHARMACODYNAMICS
• Cardiovascular effects
• decreased BP ( greater fall in systolic)
• decreased HR
• In chronically treated patients
• - SVR little affected
• - CO initially decreased, returns toward
  pre-drug levels with time.
• 2. Respiratory effects
• minimal depressant effect on ventilation
• do not potentiate depressant effects of opioids

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• Pharmacokinetics
• Oral
• rapidly absorbed
• peak plasma conc.60-90min
• Et1/2 9-12 hrs
• 2. Intravenous highly lipid soluble readily
  distributes into extra vascular sites including
  CNS

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• Pontine locus ceruleus sedation
• Medullary vasomotor response peripheral
  vasodilation, decreased BP, HR and CO.
• Modification of K channels in CNS
  (hyperpolarization of cell membranes)
• - profound decreases in anaesthetic
  requirements.
• Neuraxial administration- inhibits spinal
  substance P release nociceptive neuron firing
  due to noxious stimulation.

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• USES
• 1. Preanaesthetic medication
• Oral clonidine in preoperative period-
• a) blunts reflex tachycardia associated with
  direct laryngoscopy intubation
• b) decreases intraoperative lability of BP HR
• c) decreases plasma catecholamine concentrations
• d) dramatically decrease anaesthetic requirement
  for inhaled (MAC) injected drugs

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• 2. Analgesia
• Preservative- free clonidine administration into
  the epidural or subarachnoid space produces
  dose-dependent analgesia
• (avoiding side effects of opioids)
• - due to activation of postsynaptic alpha2
  receptors in substantia gelatinosa of spinal cord
• - Side Effect hypotension, sedation, dryness of
  mouth
• Addition of clonidine 1µ/kg to lidocaine in
  Biers Block enhances post-operative analgesia
• Intra- articular administration of clonidine
  produces analgesia after knee arthroscopies.
  

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• 3. Chronic pain
• - transdermal clonidine shown to decrease pain
  in diabetic neuropathy
• intractable pain following spinal cord injury
• reported to possess peripheral analgesic
  properties

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• 4. Prolonging the effects of regional
  anaesthesia
• Prolonged duration of sensory motor blockade in
  subarachnoid block.
• oral clonidine 150-200µg admn. 1-1.5 hrs before
  institution of S.A.B has same effect
• Increased intensity of Peripheral Nerve Blocks
• addition of clonidine to local anaesthetic

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• 5. Protection against peri-operative Myocardial
  ischaemia
• Decrease in overall mortality (superior to
  beta-blockers)
• 0.2mg oral or transdermal patch in evening before
  or on morning of surgery in patients at risk for
  CAD and continued for 4 days post-operatively

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• 6. Diagnosis of pheochromocytoma
• oral 0.3mg decreases plasma conc. in normal
  patients but not in presence of pheochromocytoma
• 7. Treatment of shivering
• 75µg i.v. clonidine stops shivering (reflects
  ability to inhibit central thermoregulatory
  control)
• 150µg i.v. effective in preventing shivering in
  patients receiving epidural anaesthesia

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• 8. Opioid alcohol withdrawal syndrome
• Clonidine 10µg/kg i.v. decreases sympathetic NS
  activity associated with cardiovascular
  stimulation attenuates increase in plasma
  catecholamine concentrations when naloxone is
  administered during G.A. to pt. addicted to
  opioids
• Effective in T/t of Alcohol withdrawal syndrome
  in pt. not responding to high doses of BZDs or
  opioids

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• SIDE- EFFECTS
• 1) Sedation
• 2) Xerostomia
• 3) Bradycardia (often requires treatment with
  anticholinergic)
• 4) Retention of sodium and water
• 5) Skin rashes
• 6) Impotence
• 7) Orthostatic hypotension (rare)

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• DOSAGE GUIDELINES (healthy
  adults)
• 1. ORAL- 30µg/kg
• 2. INTRATHECAL- 15-30µg added to local
  anaesthetic agents (max. 1µg/kg)
• 3. EPIDURAL- 50µg or 1µg/kg, whichever is lower
  (max. 2µg/kg)
• 4. INTRA-ARTICULAR- 150µg or 2µg/kg
• 5. INTRAVENOUS
• 50-75µg or 1µg/kg, whichever is lower slowly
  15 minutes prior to surgery
• Post operative/ epidural shivering- 30µg
  slow i.v.
• H.T. Crisis-150-300µg slow i.v. over 10 min
  (max. 3µg/kg)
• 6. CONTINUOUS EPIDURAL INFUSION
• starting dose-30µg/h, titrated according to
  response

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• CONTRAINDICATIONS
• Known hypersensitivity
• Brady-arrythmias or heart block
• Cardiovascular/ haemodynamic instability
• Patients on anticoagulant therapy or with
  bleeding diathesis
• Local infection at site of epidural injection
• Obstetric patients (category C)
• Lactating patients